olanzapine and Acute-Disease

The dose-response relationships of antipsychotic drugs for schizophrenia are not well defined, but such information would be important for decision making by clinicians. The authors sought to fill this gap by conducting dose-response meta-analyses.. A search of multiple electronic databases (through November 2018) was conducted for all placebo-controlled dose-finding studies for 20 second-generation antipsychotic drugs and haloperidol (oral and long-acting injectable, LAI) in people with acute schizophrenia symptoms. Dose-response curves were constructed with random-effects dose-response meta-analyses and a spline model. The outcome measure was total score reduction from baseline on the Positive and Negative Syndrome Scale or the Brief Psychiatric Rating Scale. The authors identified 95% effective doses, explored whether higher or lower doses than the currently licensed ones might be more appropriate, and derived dose equivalencies from the 95% effective doses.. Sixty-eight studies met the inclusion criteria. The 95% effective doses and the doses equivalent to 1 mg of oral risperidone, respectively, were as follows: amisulpride for patients with positive symptoms, 537 mg/day and 85.8 mg; aripiprazole, 11.5 mg/day and 1.8 mg; aripiprazole LAI (lauroxil), 463 mg every 4 weeks and 264 mg; asenapine, 15.0 mg/day and 2.4 mg; brexpiprazole, 3.36 mg/day and 0.54 mg; haloperidol, 6.3 mg/day and 1.01 mg; iloperidone, 20.13 mg/day and 3.2 mg; lurasidone, 147 mg/day and 23.5 mg; olanzapine, 15.2 mg/day and 2.4 mg; olanzapine LAI, 277 mg every 2 weeks and 3.2 mg; paliperidone, 13.4 mg/day and 2.1 mg; paliperidone LAI, 120 mg every 4 weeks and 1.53 mg; quetiapine, 482 mg/day and 77 mg; risperidone, 6.3 mg/day and 1 mg; risperidone LAI, 36.6 mg every 2 weeks and 0.42 mg; sertindole, 22.5 mg/day and 3.6 mg; and ziprasidone, 186 mg/day and 30 mg. For amisulpride and olanzapine, specific data for patients with predominant negative symptoms were available. The authors have made available on their web site a spreadsheet with this method and other updated methods that can be used to estimate dose equivalencies in practice.. In chronic schizophrenia patients with acute exacerbations, doses higher than the identified 95% effective doses may on average not provide more efficacy. For some drugs, higher than currently licensed doses might be tested in further trials, because their dose-response curves did not plateau.

Topics: Acute Disease; Administration, Oral; Antipsychotic Agents; Aripiprazole; Clozapine; Delayed-Action Preparations; Dose-Response Relationship, Drug; Haloperidol; Humans; Imidazoles; Indoles; Isoxazoles; Lurasidone Hydrochloride; Olanzapine; Paliperidone Palmitate; Piperazines; Piperidines; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Schizophrenic Psychology; Thiazoles; Thiophenes

People experiencing acute psychotic illnesses, especially those associated with agitated or violent behaviour, may require urgent pharmacological tranquillisation or sedation. Droperidol, a butyrophenone antipsychotic, has been used for this purpose in several countries.. To estimate the effects of droperidol, including its cost-effectiveness, when compared to placebo, other 'standard' or 'non-standard' treatments, or other forms of management of psychotic illness, in controlling acutely disturbed behaviour and reducing psychotic symptoms in people with schizophrenia-like illnesses.. We updated previous searches by searching the Cochrane Schizophrenia Group Register (18 December 2015). We searched references of all identified studies for further trial citations and contacted authors of trials. We supplemented these electronic searches by handsearching reference lists and contacting both the pharmaceutical industry and relevant authors.. We included all randomised controlled trials (RCTs) with useable data that compared droperidol to any other treatment for people acutely ill with suspected acute psychotic illnesses, including schizophrenia, schizoaffective disorder, mixed affective disorders, the manic phase of bipolar disorder or a brief psychotic episode.. For included studies, we assessed quality, risk of bias and extracted data. We excluded data when more than 50% of participants were lost to follow-up. For binary outcomes, we calculated standard estimates of risk ratio (RR) and the corresponding 95% confidence intervals (CI). We created a 'Summary of findings' table using GRADE.. We identified four relevant trials from the update search (previous version of this review included only two trials). When droperidol was compared with placebo, for the outcome of tranquillisation or asleep by 30 minutes we found evidence of a clear difference (1 RCT, N = 227, RR 1.18, 95% CI 1.05 to 1.31, high-quality evidence). There was a clear demonstration of reduced risk of needing additional medication after 60 minutes for the droperidol group (1 RCT, N = 227, RR 0.55, 95% CI 0.36 to 0.85, high-quality evidence). There was no evidence that droperidol caused more cardiovascular arrhythmia (1 RCT, N = 227, RR 0.34, 95% CI 0.01 to 8.31, moderate-quality evidence) and respiratory airway obstruction (1 RCT, N = 227, RR 0.62, 95% CI 0.15 to 2.52, low-quality evidence) than placebo. For 'being ready for discharge', there was no clear difference between groups (1 RCT, N = 227, RR 1.16, 95% CI 0.90 to 1.48, high-quality evidence). There were no data for mental state and costs.Similarly, when droperidol was compared to haloperidol, for the outcome of tranquillisation or asleep by 30 minutes we found evidence of a clear difference (1 RCT, N = 228, RR 1.01, 95% CI 0.93 to 1.09, high-quality evidence). There was a clear demonstration of reduced risk of needing additional medication after 60 minutes for participants in the droperidol group (2 RCTs, N = 255, RR 0.37, 95% CI 0.16 to 0.90, high-quality evidence). There was no evidence that droperidol caused more cardiovascular hypotension (1 RCT, N = 228, RR 2.80, 95% CI 0.30 to 26.49,moderate-quality evidence) and cardiovascular hypotension/desaturation (1 RCT, N = 228, RR 2.80, 95% CI 0.12 to 67.98, low-quality evidence) than haloperidol. There was no suggestion that use of droperidol was unsafe. For mental state, there was no evidence of clear difference between the efficacy of droperidol compared to haloperidol (Scale for Quantification of Psychotic Symptom Severity, 1 RCT, N = 40, mean difference (MD) 0.11, 95% CI -0.07 to 0.29, low-quality evidence). There were no data for service use and costs.Whereas, when droperidol was compared with midazolam, for the outcome of tranquillisation or asleep by 30 minutes we found droperidol to be less acutely tranquillising than midazolam (1 RCT, N = 153, RR 0.96, 95% CI 0.72 to 1.28, high-quality evidence). As regards the 'need for additional medication by 60 minutes after initial adequate sedation, we found an effect (1 RCT, N = 153, RR 0.54, 95% CI 0.24 to 1.20, moderate. Previously, the use of droperidol was justified based on experience rather than evidence from well-conducted and reported randomised trials. However, this update found high-quality evidence with minimal risk of bias to support the use of droperidol for acute psychosis. Also, we found no evidence to suggest that droperidol should not be a treatment option for people acutely ill and disturbed because of serious mental illnesses.

Topics: Acute Disease; Aggression; Antipsychotic Agents; Benzodiazepines; Droperidol; Haloperidol; Humans; Midazolam; Olanzapine; Psychomotor Agitation; Psychotic Disorders; Randomized Controlled Trials as Topic

Serotonin syndrome is a potentially life-threatening complication of serotonergic agents. Although mirtazapine is a relatively safe antidepressant and has a comparatively low incidence of side effects, it still could induce serotonin syndrome.. We described a 34-year-old man with schizophrenic disorder who presented with acute consciousness disturbance, extremely high fever, rigidity, and spontaneous clonus in lower limbs. Two days before entry, oral mirtazapine was added to his regular medication of olanzapine. The serotonin-related symptoms resolved soon after withdrawal of mirtazapine and olanzapine combined with treatment with intravenous benzodiazepine and oral cyproheptadine. However, the clinical course was complicated by rhabdomyolysis, acute renal failure, and acute pulmonary edema. After receiving mechanical ventilation, hemodialysis, and appropriate supportive treatment, his general condition recovered and he was discharged without any neurological sequelae.. With the increasing use of serotonergic agents, awareness of serotonin syndrome is important. Early diagnosis and timely discontinuation of the offending agent(s) are imperative to prevent morbidity and mortality.

Topics: Acute Disease; Acute Kidney Injury; Adult; Benzodiazepines; Humans; Male; Mianserin; Mirtazapine; Olanzapine; Pulmonary Edema; Rhabdomyolysis; Serotonin Syndrome

Patients with bipolar disorder are symptomatic about half of the time, experiencing depression more often than mania/hypomania. Because patients usually seek treatment during a depressive episode (rather than a manic episode), bipolar depression is commonly misdiagnosed as unipolar depression. Providing an accurate and timely bipolar depression diagnosis is critical for the proper treatment of the patient. Some FDA-approved treatments are helpful during acute and maintenance phases of therapy, but there is a significant unmet need for effective bipolar depression treatments with favorable side-effect profiles. Newer agents offer the promise of improvements in tolerability, but additional research is needed to actualize this promise into better treatments for patients struggling with bipolar depression.

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depression; Dibenzothiazepines; Drug Therapy, Combination; Fluoxetine; Humans; Isoindoles; Lurasidone Hydrochloride; Olanzapine; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors; Thiazoles

Acute psychotic illness, especially when associated with agitated or violent behaviour, can require urgent pharmacological tranquillisation or sedation. In several countries, clinicians often use benzodiazepines (either alone or in combination with antipsychotics) for this outcome.. To estimate the effects of benzodiazepines, alone or in combination with antipsychotics, when compared with placebo or antipsychotics, alone or in combination with antihistamines, to control disturbed behaviour and reduce psychotic symptoms.. We searched the Cochrane Schizophrenia Group's register (January 2012), inspected reference lists of included and excluded studies and contacted authors of relevant studies.. We included all randomised clinical trials (RCTs) comparing benzodiazepines alone or in combination with any antipsychotics, versus antipsychotics alone or in combination with any other antipsychotics, benzodiazepines or antihistamines, for people with acute psychotic illnesses.. We reliably selected studies, quality assessed them and extracted data. For binary outcomes, we calculated standard estimates of relative risk (RR) and their 95% confidence intervals (CI) using a fixed-effect model. For continuous outcomes, we calculated the mean difference (MD) between groups. If heterogeneity was identified, this was explored using a random-effects model.. We included 21 trials with a total of n = 1968 participants. There was no significant difference for most outcomes in the one trial that compared benzodiazepines with placebo, although there was a higher risk of no improvement in people receiving placebo in the medium term (one to 48 hours) (n = 102, 1 RCT, RR 0.62, 95% CI 0.40 to 0.97, very low quality evidence). There was no difference in the number of participants who had not improved in the medium term when benzodiazepines were compared with antipsychotics (n = 308, 5 RCTs, RR 1.10, 95% CI 0.85 to 1.42, low quality evidence); however, people receiving benzodiazepines were less likely to experience extrapyramidal effects (EPS) in the medium term (n = 536, 8 RCTs, RR 0.15, 95% CI 0.06 to 0.39, moderate quality of evidence). Data comparing combined benzodiazepines and antipsychotics versus benzodiazepines alone did not yield any significant results. When comparing combined benzodiazepines/antipsychotics (all studies compared haloperidol) with the same antipsychotics alone (haloperidol), there was no difference between groups in improvement in the medium term (n = 155, 3 RCTs, RR 1.27, 95% CI 0.94 to 1.70, very low quality evidence) but sedation was more likely in people who received the combination therapy (n = 172, 3 RCTs, RR 1.75, 95% CI 1.14 to 2.67, very low quality evidence). However, more participants receiving combined benzodiazepines and haloperidol had not improved by medium term when compared to participants receiving olanzapine (n = 60,1 RCT, RR 25.00, 95% CI 1.55 to 403.99, very low quality evidence) or ziprasidone (n = 60, 1 RCT, RR 4.00, 95% CI 1.25 to 12.75 very low quality evidence). When haloperidol and midazolam were compared with olanzapine, there was some evidence the combination was superior in terms of improvement, sedation and behaviour.. The evidence from trials for the use of benzodiazepines alone is not good. There were relatively little good data and most trials are too small to highlight differences in either positive or negative effects. Adding a benzodiazepine to other drugs does not seem to confer clear advantage and has potential for adding unnecessary adverse effects. Sole use of older antipsychotics unaccompanied by anticholinergic drugs seems difficult to justify. Much more high quality research is needed in this area.

Topics: Acute Disease; Aggression; Anti-Dyskinesia Agents; Antipsychotic Agents; Benzodiazepines; Drug Therapy, Combination; Emergency Treatment; Haloperidol; Humans; Lorazepam; Olanzapine; Psychomotor Agitation; Psychotic Disorders; Randomized Controlled Trials as Topic

Treatment of acute mania with second-generation antipsychotics has been claimed to involve a lower risk of switch to depression than haloperidol. However, clinical guidelines clearly state that this is not a proven fact.. Meta-analysis of double-blind randomized controlled trials in acute mania, comparing rates of switch to depression with atypical antipsychotics and with haloperidol. Search was conducted in MEDLINE and CENTRAL databases (last search: September 2011).. 8 randomized clinical trials fulfilled inclusion criteria. 2 of them were excluded because of low methodological quality or lack of data. 5 second-generation antipsychotics (aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone) were compared to haloperidol. In the mixed effects model the Risk Ratio for depressive switch was 0.71 (0.52, 0.96) favouring atypical antipsychotics. In the random effects model the difference did not reach statistical significance. In the heterogeneity analysis, exclusion of an outlying aripiprazole trial yielded a Risk Ratio of 0.58 (0.42, 0.82) with a non-significant heterogeneity test. Although no atypical antipsychotic was individually significantly superior to haloperidol, a trend could be seen favouring olanzapine (RR=0.56 [0.29, 1.08]), quetiapine (RR=0.36 [0.10, 1.33]), and ziprasidone (RR=0.51 [0.22, 1.18]).. All trials were industry supported, with some variability in dosage of haloperidol. Switch to depression was not the primary outcome of the trials. Heterogeneity could be explained as a lack of class-effect for atypicals.. Treating acute mania with atypicals is associated to 42% less risk of switch to depression than with haloperidol. Nevertheless, caution should be taken when considering this a class effect, as only olanzapine, quetiapine, and ziprasidone may show a better profile.

Topics: Acute Disease; Antimanic Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Depression; Depressive Disorder; Dibenzothiazepines; Double-Blind Method; Drug Industry; Haloperidol; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Research Support as Topic; Risperidone; Thiazoles

Individuals with bipolar disorder are euthymic approximately half of the time, but recurring mood episodes are common, and time spent ill is predominated by depressive symptoms. Despite the prevalence of depression in bipolar disorder, evidence suggests that antidepressants are not likely to benefit most patients. Lithium, long considered a first-line treatment for bipolar disorder, is not the most effective agent for preventing bipolar depression. This article reviews multiple pharmacologic options that should be considered by clinicians treating bipolar disorder in both acute and maintenance phases.

Topics: Acute Disease; Adverse Drug Reaction Reporting Systems; Affect; Anticonvulsants; Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Diagnosis, Differential; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Therapy, Combination; Fluoxetine; Humans; Lithium Carbonate; Long-Term Care; Olanzapine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Treatment Outcome; United States; United States Food and Drug Administration

Topics: Acute Disease; Aggression; Antipsychotic Agents; Benzodiazepines; Controlled Clinical Trials as Topic; Haloperidol; Humans; Injections, Intramuscular; Irritable Mood; Olanzapine; Psychiatric Status Rating Scales; Psychomotor Agitation; Schizophrenia; Schizophrenic Language; Schizophrenic Psychology; Treatment Outcome; Verbal Behavior

Olanzapin is an atypical antipsychotic drug, which is approved for use in acute mania and in the prophylaxis of bipolar disorder. There are eight double-blind, placebo-controlled studies, which show its efficacy in the treatment of acute mania, five, which document its efficacy in the long-term treatment of bipolar disorder and one that shows its use in bipolar depression. The following overview presents and critically evaluates these studies. Quality of life aspects on olanzapine treatment and the safety profile of the drug will also be discussed.

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Biological Availability; Bipolar Disorder; Brain; Clinical Trials as Topic; Controlled Clinical Trials as Topic; Double-Blind Method; Drug Therapy, Combination; Humans; Olanzapine; Quality of Life; Treatment Outcome

Agitation is common in patients with acute schizophrenia or bipolar mania, and when severe can result in aggressive or violent behaviour. Pharmacotherapy for acute psychotic agitation includes the use of antipsychotic and benzodiazepine drugs, either alone or in combination. Although oral treatment is preferred, options in the pharmacotherapy of acute agitation include the parenteral administration of antipsychotics in order to facilitate onset of drug action and quickly alleviate symptoms. Until recently only conventional antipsychotic and benzodiazepine drugs were available as intramuscular injections. Olanzapine has been one of the first atypical antipsychotics available for intramuscular administration. Four randomized placebo and comparator controlled , double-blind clinical trials have demonstrated the efficacy of olanzapine in reducing acute agitation in patients with schizophrenia, bipolar mania and Alzheimer and vascular dementia. Evidence from these clinical trials has shown that IM olanzapine associated with faster onset of action and more favorable profile of adverse events, than monotherapy with IM haloperidol. Current clinical experience and one naturalistic study with intramuscular olanzapine suggest that it is efficacious and can be safely used in "real world" patients with severe agitation. Intramuscular olanzapine have shown ease of transition to same agent oral therapy once the acute agitation has diminished. The orally disintegrating tablet formulation of olanzapine was effective rapidly reducing psychopathology, while improving medication compliance, attitudes and behaviours. This new formulation of olanzapine may offer an alternative strategy in the treatment of acutely ill, noncompliant schizophrenic patients. Evidence suggests that the new formulations of olanzapine should be among the first-line choices in the treatment of agitation in acute psychosis.. olanzapine, intramuscular, orally disintegrating tablet, agitation, psychosis.

Topics: Acute Disease; Administration, Oral; Antipsychotic Agents; Attitude; Benzodiazepines; Bipolar Disorder; Dementia; Humans; Injections, Intramuscular; Olanzapine; Patient Compliance; Psychomotor Agitation; Psychotic Disorders; Schizophrenia; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

Intramuscular olanzapine (Zyprexa) is a rapid-acting atypical antipsychotic drug that is also indicated for use in patients with agitation associated with schizophrenia or bipolar mania, the focus of this review. Evidence from three well designed trials indicates that this formulation of olanzapine is at least as effective as intramuscular haloperidol or lorazepam in the treatment of patients with acute agitation associated with schizophrenia or bipolar mania, and has a faster onset of action. Although transient reductions in blood pressure and heart rate may occur in some patients administered intramuscular olanzapine, preliminary evidence of a general lack of clinical effect on the corrected QT (QTc) interval and a low incidence of extrapyramidal symptoms (EPS) is promising. The parenteral formulation of olanzapine appears to offer an effective, fast-acting and generally well tolerated alternative in the treatment of this significant behavioural problem.

Topics: Acute Disease; Benzodiazepines; Dose-Response Relationship, Drug; Drug Administration Routes; Drug Administration Schedule; Drug Tolerance; Humans; Injections, Intramuscular; Olanzapine; Psychiatric Status Rating Scales; Psychomotor Agitation; Selective Serotonin Reuptake Inhibitors; Time Factors; Treatment Outcome

A key goal of the pharmacologic treatment of acute bipolar mania is rapid symptom improvement. Medications commonly used to attain this goal include lithium, several anticonvulsants, and both first- and second-generation antipsychotics. Second-generation antipsychotics, which are associated with substantially lower rates of extrapyramidal side effects than first-generation agents, are becoming a mainstay in the treatment of acute mania. Although their efficacy appears to be comparable, second-generation antipsychotics may differ in time to onset and in their side effect profiles. Therefore, selecting a second-generation antipsychotic requires consideration of how an agent's efficacy, onset of action, and adverse events profile influence its appropriateness for each patient.

Topics: Acute Disease; Anticonvulsants; Antipsychotic Agents; Aripiprazole; Basal Ganglia Diseases; Benzodiazepines; Bipolar Disorder; Clozapine; Dibenzothiazepines; Double-Blind Method; Humans; Lithium; Olanzapine; Piperazines; Placebos; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risperidone; Treatment Outcome

Vieta E, Goikolea JM. Atypical antipsychotics: newer options for mania and maintenance therapy. Bipolar Disord 2005: 7 (Suppl. 4): 21-33. (c) Blackwell Munksgaard, 2005Atypical antipsychotics have been used to treat patients with schizophrenia for many years, but now there is increasing evidence of their utility in the treatment of bipolar disorder. In the past few years several atypical agents have received regulatory approval for use in bipolar mania. Through a review of randomized controlled trials for five commonly used atypical drugs, olanzapine, risperidone, quetiapine, ziprasidone and aripiprazole, this article evaluates their efficacy in the acute and maintenance phases of bipolar disorder. The evidence shows that atypical antipsychotics are effective in the treatment of manic symptoms, either alone or in combination with traditional mood stabilizers such as lithium and divalproex. Although emerging data indicate that atypical antipsychotics will be a promising addition to those therapies that are currently available for managing patients during the maintenance phase of bipolar illness, their potential in the long-term management of bipolar disorder remains to be fully explored. Atypical antipsychotics appear to have broadly similar efficacy against manic symptoms of bipolar disorder, but there are important differences in their tolerability profiles, which are likely to be of particular relevance during long-term treatment. A brief assessment of tolerability issues surrounding the use of atypical agents in bipolar disorder and other aspects of treatment that have impact on the clinical effectiveness of the therapy are considered.

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Humans; Lithium Carbonate; Olanzapine; Piperazines; Quetiapine Fumarate; Risperidone; Thiazoles

Depressive episodes are significant in bipolar illness since patients can spend up to one-third of their lives in depression. Although the treatment of bipolar depression remains an understudied area, new data from randomized, controlled trials and naturalistic studies have expanded the range of treatments available. The main aim in the treatment of bipolar depression is the prevention of the patient switching to mania and cycle acceleration, and antidepressant therapy may be contraindicated because of the risk for switching. Guidelines for the acute treatment of bipolar depression emphasize treatment with a mood stabilizer, of which lithium has been the most thoroughly studied in randomized, controlled trials in acute bipolar depression. Lamotrigine has also demonstrated significant efficacy in recent studies and has been approved by the FDA.

Topics: Acute Disease; Antidepressive Agents; Antimanic Agents; Benzodiazepines; Bipolar Disorder; Chemoprevention; Contraindications; Depressive Disorder; Diagnosis, Differential; Drug Therapy, Combination; Humans; Lamotrigine; Lithium; Olanzapine; Triazines; Valproic Acid

Topics: Acute Disease; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Humans; Lithium Compounds; Olanzapine; Pirenzepine; Valproic Acid

Topics: Acute Disease; Affect; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Chronic Disease; Drug Administration Schedule; Humans; Lithium Compounds; Olanzapine; Pirenzepine; Treatment Outcome; Valproic Acid

The frequency and severity of extrapyramidal syndrome (EPS) were evaluated in patients with DSM-III or DSM-IV schizophrenia in the acute phase (- 8 weeks) of randomized, double-blind, controlled trials from the integrated olanzapine clinical trial database.. This retrospective analysis included 23 clinical trials and 4611 patients from November 11, 1991, through July 31, 2001. Incidences of dystonic, parkinsonian, and akathisia events were compared using treatment-emergent adverse-event data. Categorical analyses of Simpson-Angus Scale and Barnes Akathisia Scale (BAS) scores, use of anticholinergic medications, and baseline-to-endpoint changes in Simpson-Angus Scale and BAS scores were compared.. A significantly smaller percentage of olanzapine-treated patients experienced dystonic events than did haloperidol- (p <.001) or risperidone-treated patients (p =.047). A significantly greater percentage of haloperidol-treated patients experienced parkinsonian (p <.001) and akathisia (p <.001) events than did olanzapine-treated patients. Categorical analysis of Simpson-Angus Scale scores showed significantly more haloperidol- (p <.001) or risperidone-treated patients (p =.004) developed parkinsonism than did olanzapine-treated patients. Olanzapine-treated patients experienced significantly greater reductions in Simpson-Angus Scale scores than did haloperidol- (p <.001), risperidone- (p <.001), or clozapine-treated (p =.032) patients. Categorical analysis of BAS scores showed significantly more haloperidol-treated patients experienced treatment-emergent akathisia versus olanzapine-treated patients (p <.001). Significantly greater reductions in BAS scores were experienced during olanzapine treatment versus placebo (p =.007), haloperidol (p <.001), and risperidone (p =.004) treatments. A significantly smaller percentage of olanzapine-treated patients received anticholinergic medications compared with that of haloperidol- (p <.001) or risperidone-treated patients (p =.018). Compared with that in olanzapine-treated patients, the duration of anticholinergic cotreatment was significantly longer among haloperidol- (p <.001) or risperidone-treated patients (p =.040) and significantly shorter among clozapine-treated patients (p =.021).. This analysis of available data from olanzapine clinical trials lends additional support to olanzapine's favorable EPS profile.

Topics: Acute Disease; Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Cholinergic Antagonists; Clozapine; Double-Blind Method; Female; Haloperidol; Humans; Male; Olanzapine; Pirenzepine; Placebos; Randomized Controlled Trials as Topic; Retrospective Studies; Risperidone; Schizophrenia

Previous studies have examined the safety and tolerability of oral-loaded divalproex sodium in the treatment of acute mania, but not the early efficacy of this dosing strategy. The purpose of this study was to evaluate the early efficacy of oral-loaded divalproex.. In this pooled analysis, 348 subjects from 3 randomized, double-blind, parallel-group, active- or placebo-controlled studies were used to compare the efficacy, safety, and tolerability of oral-loaded divalproex with standard-titration divalproex, lithium, olanzapine, or placebo. Subjects were inpatients diagnosed with acute mania associated with bipolar I disorder (DSM-III-R or -IV and SADS-Change Version). Patients were administered oral-loaded divalproex (20 or 30 mg/kg/day on days 1 and 2 followed by 20 mg/kg/day, and increased at physician's discretion), standard-titration divalproex initiated at 250 mg t.i.d. and titrated to 40-150 microg/mL, lithium (300 mg t.i.d. initial dose) titrated to 0.4 to 1.5 mEq/L, olanzapine (10 mg q.d. initial dose) up to 20 mg/day, or placebo.. The results demonstrate an early efficacy advantage for oral-loaded divalproex compared to standard-titration divalproex at days 5, 7/8, and 10. Efficacy was improved over lithium on day 7/8. There were no efficacy differences between divalproex loading and olanzapine. Divalproex loading showed greater efficacy than placebo at all time points. Divalproex loading was as well tolerated or better tolerated than the other active treatments as measured by adverse events and changes in laboratory parameters.. These results suggest the oral loading of divalproex leads to a more rapid antimanic effect when compared with standard-titration divalproex, lithium, or placebo and is better tolerated than olanzapine and as well tolerated as lithium or standard-titration divalproex.

Topics: Acute Disease; Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Drug Tolerance; Female; Humans; Lithium; Male; Middle Aged; Olanzapine; Pirenzepine; Randomized Controlled Trials as Topic; Severity of Illness Index; Titrimetry; Treatment Outcome; Valproic Acid

The term bipolar disorder is no longer limited to the classical manic-depressive condition, but now subsumes a wide spectrum of illnesses. As a consequence of this expansion of the classification systems, the therapeutic utility of lithium and other mood stabilizing agents has to be defined anew. The majority treatment recommendations differentiate, symptom-related, between euphoric mania, mixed conditions, mania with psychotic symptoms and rapid cycling manic episodes. Current acute treatment includes, in addition to lithium, in particular carbamazepine and valproate, but also newer antiepileptic drugs such as lamotrigine or atypical neuroleptic agents such as olanzapine and risperidone. Due to the high suicidal risk, patients with bipolar depression often need to be given an antidepressant as well. It must, however, be remembered that in patients with rapid cycling, antidepressants may re-trigger mania.

Topics: Acute Disease; Algorithms; Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Carbamazepine; Drug Therapy, Combination; Humans; Isotopes; Lamotrigine; Lithium; Olanzapine; Pirenzepine; Risperidone; Selective Serotonin Reuptake Inhibitors; Serotonin Antagonists; Triazines; Valproic Acid

Patients with bipolar disorder frequently receive antipsychotic agents during both the acute and maintenance phases of treatment. Conventional antipsychotics are effective against mania, but they may induce depressive symptoms and expose patients with bipolar disorder to increased risks of tardive dyskinesia. Recent studies have shown risperidone to be effective for acute mania, both as monotherapy and in combination with mood stabilizers; this agent has also shown efficacy as add-on maintenance therapy in open-label studies as it exhibited both antimanic and antidepressant effects. Olanzapine, another novel antipsychotic, is also effective against both manic and depressive symptoms and in the maintenance treatment as indicated by an open-label study. Data on other novel agents are more limited.

Topics: Acute Disease; Antimanic Agents; Benzodiazepines; Bipolar Disorder; Haloperidol; Humans; Lithium; Olanzapine; Pirenzepine; Randomized Controlled Trials as Topic; Risperidone

Alterations of electrocardiogram results and cases of sudden cardiac death have been reported since the beginning of neuroleptic treatment. In particular, a temporal association exists between some antipsychotics and prolongation of the heart rate-corrected QT interval (QTc), an event that may increase the risk for developing a potentially fatal ventricular tachycardia arrhythmia known as torsades de pointes if it significantly exceeds normal intraindividual and interindividual variation. Although the incidence of serious adverse cardiac events in response to antipsychotic medications is relatively low, any possibility for the occurrence of cardiotoxicity warrants continued study. The present article reviews important differences among antipsychotic drugs in the potential for, and occurrence of, serious adverse cardiac outcomes and suggests that olanzapine, as therapeutically administered to patients with schizophrenia and related psychoses, does not contribute significantly to a QTc prolongation that could result in potentially fatal ventricular arrhythmias.

Topics: Acute Disease; Antipsychotic Agents; Arrhythmias, Cardiac; Benzodiazepines; Death, Sudden; Female; Humans; Long QT Syndrome; Male; Olanzapine; Pirenzepine; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Torsades de Pointes

For patients hospitalized with acute episodes of psychosis, rapid stabilization of intense positive symptoms, hostility, and agitation is typically a preeminent therapeutic goal. These goals often differ from those of the nonhospitalized patient with psychosis for whom long-term treatment goals such as improvement of negative symptoms, cognitive function, compliance, and reduction in side effect burden may be paramount. Therefore, when selecting an antipsychotic treatment for hospitalized patients, efficacy against positive symptoms and hostility as well as speed of therapeutic onset should strongly be considered. At the same time, selection of antipsychotic treatment in the inpatient setting should establish a definitive treatment that will address long-term goals effectively after discharge. This article presents the rationale and practical guidelines for selection of treatment regimens for patients hospitalized due to acute psychosis.

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Clozapine; Drug Administration Schedule; Drug Therapy, Combination; Haloperidol; Hospitalization; Hostility; Humans; Olanzapine; Pirenzepine; Practice Guidelines as Topic; Psychomotor Agitation; Psychotic Disorders; Risperidone; Treatment Outcome

Atypical neuroleptic agents are an excellent, safer, and more effective alternative to the widespread practice of maintenance adjunctive treatment with traditional neuroleptic agents in patients with bipolar disorder. Currently, a number of prospective studies are available with clozapine, risperidone, olanzapine, and quetiapine in the treatment of bipolar disorder. Most are short-term studies, although longer-term data are becoming available. Four double-blind studies of acute mania have been conducted with risperidone and olanzapine, leading to recent Food and Drug Administration approval for olanzapine in the indication of acute mania. Given the limited longer-term data, and the evidence for mostly adjunctive benefits with these agents, it seems unlikely that these agents will prove to be primary mood stabilizers in their own right. Nonetheless, they serve an important role as adjunctive treatments along with standard mood stabilizers in the rational polypharmacy of bipolar disorder. To date, differences in efficacy have not been established. However, differences in the side effect of weight gain may be even more relevant in bipolar disorder than in schizophrenia due to the need to use standard mood stabilizers that often potentiate such weight gain.

Topics: Acute Disease; Algorithms; Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Dibenzothiazepines; Drug Therapy, Combination; Humans; Lithium; Olanzapine; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Treatment Outcome; Valproic Acid

Bipolar disorder is a lifelong episodic condition characterized by mood swings between mania and depression. In the United States alone, approximately 4 million people are affected by this disorder. Pharmacologic treatment for acute manic episodes or as maintenance therapy includes lithium, valproate, carbamazepine, and typical antipsychotics. However, many patients fail to respond to these treatments due to lack of efficacy or production of side effects leading to patient noncompliance. Non-compliance with pharmacologic treatment is indeed a major risk factor in bipolar disorder patients and needs to be managed with ongoing education, psychotherapy, and a simplified but effective pharmacologic treatment regimen. Recently introduced novel antipsychotics show much promise as mood-stabilizing agents in bipolar patients, with minimal risk of treatment-emergent extrapyramidal symptoms and tardive dyskinesia. Nonetheless, further research is warranted to help clarify the role of novel antipsychotics in the treatment of bipolar disorder.

Topics: Acute Disease; Algorithms; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Carbamazepine; Clinical Trials as Topic; Humans; Lithium; Olanzapine; Pirenzepine; Research Design; Risk Factors; Treatment Outcome; Treatment Refusal; Valproic Acid

Antipsychotic agents have been used commonly in the treatment of bipolar disorder. This article reviews the evolution of the use of antipsychotic agents and their role in the acute and maintenance treatment of bipolar disorder. The focus is on neuroleptic drugs, the atypical antipsychotic drugs (risperidone and clozapine), and two fo the new atypical antipsychotic drugs that were recently approved.

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Clozapine; Delayed-Action Preparations; Drug Therapy, Combination; Humans; Lithium; Olanzapine; Pirenzepine; Psychotic Disorders; Risperidone; Treatment Outcome

The author reviews the evolution of emergency psychiatric practice over the past 20 years--from the concept of high-dose antipsychotic medication to the more rational treatment approach for acute psychosis made possible by modern pharmacodynamic insight and the availability of new pharmacotherapeutic agents. A decision tree for current practice in the rapid tranquilization of agitated, apparently psychotic patients is described.

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Clozapine; Decision Trees; Drug Administration Schedule; Emergency Services, Psychiatric; Emergency Treatment; Haloperidol; History, 20th Century; Humans; Lorazepam; Olanzapine; Pirenzepine; Psychotic Disorders; Risperidone

When a patient with an acute exacerbation of schizophrenia is admitted into the hospital, the target symptoms include pathologic excitement/agitation and exacerbated psychotic symptoms. The goal of hospitalization becomes attenuation of these symptoms to a level compatible with safe discharge. The mainstay of stabilization is antipsychotic treatment. A risk/benefit analysis of the conventional versus the newer antipsychotics favors the use of the newer agents as first-line drugs. These newer antipsychotic agents represent the first significant advance in the pharmacologic treatment of schizophrenia in the past four decades. They are at least as effective as conventional agents and are clearly superior from a safety perspective. Because of short inpatient stays, the challenge for clinicians is to provide an adequate treatment period without aggressively escalating the dose.

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Drug Administration Schedule; Hospitalization; Humans; Length of Stay; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risk Assessment; Risperidone; Schizophrenia; Schizophrenic Psychology

Olanzapine is a new "atypical" antipsychotic agent that belongs chemically to the thienobenzodiazepine class. Its relatively greater binding affinity for 5-HT2 compared to D2 receptors makes it similar to the atypical agent clozapine, a serotonin/dopamine antagonist. Four double-blind pivotal studies, which compare olanzapine to placebo and/or haloperidol, are presented. The results suggest that olanzapine is as effective as haloperidol for positive symptoms and more effective than haloperidol for the treatment of the negative symptoms of schizophrenia.

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Haloperidol; Humans; Male; Multicenter Studies as Topic; Olanzapine; Pirenzepine; Placebos; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Clinical safety data for treatment of acute schizophrenia with olanzapine, a new atypical antipsychotic agent, are summarized. The primary clinical trial safety database included 2500 patients treated with olanzapine, 810 with haloperidol, and 236 with placebo. The overall discontinuation rate from olanzapine treatment was low. Significant adverse events included somnolence, weight gain, and asymptomatic treatment-emergent transaminase elevation. Minimal parkinsonism and akathisia with rare dystonia were noted. No hematotoxicity was noted. The incidence of seizures and sexual dysfunction was rare.

Topics: Acute Disease; Akathisia, Drug-Induced; Antipsychotic Agents; Benzodiazepines; Blood Pressure; Clinical Trials as Topic; Cross-Over Studies; Dizziness; Double-Blind Method; Dystonia; Haloperidol; Heart Rate; Humans; Liver; Olanzapine; Parkinson Disease, Secondary; Pirenzepine; Placebos; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic; Schizophrenia; Schizophrenic Psychology; Sleep; Transaminases; Treatment Outcome; Weight Gain

This report presents the rationale and design of a multi-center clinical trial that examines the efficacy and safety of antipsychotic combination treatment in acutely ill schizophrenia patients compared to antipsychotic monotherapy. Antipsychotic combination treatment is common in clinical practice worldwide, despite clinical guidelines generally not recommending such practice due to lacking evidence for its efficacy and safety. Olanzapine has a related chemical structure and comparable receptor-binding profile as clozapine, which demonstrated superior efficacy in combination studies, but has a more unfavorable side-effect profile compared to olanzapine. Amisulpride and olanzapine have shown promising therapeutic efficacy in meta-analyses in monotherapy for people with schizophrenia. Combining amisulpride and olanzapine, complementary receptor-binding properties may enhance efficacy and possibly reduce (or at least not augment) side effects due to the different receptor profiles and metabolization pathways. Accordingly, we hypothesize that patients treated with amisulpride plus olanzapine show greater improvement on the Positive and Negative Syndrome Scale total score after 8 weeks versus either monotherapy. A randomized, double-blind controlled trial is performed at 16 German centers comparing flexibly dosed monotherapy of oral amisulpride (400-800 mg/day), and olanzapine (10-20 mg/day) and amisulpride-olanzapine co-treatment. Sample size was calculated to be n = 101 per treatment arm, assuming an effect size of 0.500 and a two-sided alpha = 0.025 and beta = 0.90. Recruitment for this trial started in June 2012. Until December 2018, 328 patients have been randomized. Trial conduct has been extended to reach the projected sample size. Publication of the study results is expected in 2019 informing an evidence-based recommendation regarding specific antipsychotic combination treatment.

Topics: Acute Disease; Adolescent; Adult; Aged; Amisulpride; Antipsychotic Agents; Double-Blind Method; Drug Therapy, Combination; Humans; Middle Aged; Multicenter Studies as Topic; Olanzapine; Randomized Controlled Trials as Topic; Research Design; Schizophrenia; Young Adult

To assess the antipsychotic efficacy and safety of a combination of olanzapine and samidorphan (OLZ/SAM).. This 4-week, phase 3, randomized, double-blind, placebo- and olanzapine-controlled study was conducted from December 2015 to June 2017 in adults with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria who were experiencing an acute exacerbation. Patients were randomized 1:1:1 to OLZ/SAM, olanzapine monotherapy, or placebo. The primary and key secondary efficacy endpoint assessed was the change in Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions-Severity of Illness Scale (CGI-S) score between baseline and week 4, respectively, for OLZ/SAM versus placebo. Safety monitoring occurred throughout.. 401 patients received ≥ 1 dose of study drug; 352 completed treatment. Treatment with OLZ/SAM resulted in significant improvements versus placebo in PANSS total and CGI-S scores from baseline to week 4 (least squares [LS] mean ± SE: -6.4 ± 1.8 [P < .001] and -0.38 ± 0.12 [P = .002], respectively). Olanzapine treatment resulted in similar improvements (PANSS and CGI-S LS mean ± SE of -5.3 ± 1.84 [P = .004] and -0.44 ± 0.12 [P < .001], respectively). Adverse events (AEs) occurred in 54.5%, 54.9%, and 44.8% of patients on OLZ/SAM, olanzapine, and placebo, respectively. Weight gain, somnolence, dry mouth, anxiety, and headache were the most common AEs (ie, ≥ 5%) with active treatment.. OLZ/SAM treatment resulted in statistically and clinically significant efficacy improvements over 4 weeks versus placebo in adults with acutely exacerbated schizophrenia. Improvements were similar to those observed with olanzapine. OLZ/SAM was well tolerated, with a safety profile similar to that of olanzapine.. ClinicalTrials.gov identifier: NCT02634346; EudraCT number: 2015-003373-15​​.

Topics: Acute Disease; Adult; Antipsychotic Agents; Double-Blind Method; Drug Combinations; Female; Humans; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Olanzapine; Outcome Assessment, Health Care; Schizophrenia; Symptom Flare Up

This study was conducted to evaluate the efficacy and metabolic effects of paliperidone palmitate (PP) injections against oral olanzapine in first-episode schizophrenia (FES) patients.. Eligible patients were randomized to receive PP or olanzapine. Efficacy assessments and weight-related parameters were assessed at baseline, weeks 1, 5, 9, and endpoint or at early withdrawal. Lipid, glucose, insulin and prolactin were evaluated at baseline and endpoint or at early withdrawal.. The Positive And Negative Syndrome Scale (PANSS) scores declined significantly after treatment in both groups. Significant increases in weight-related parameters from baseline to endpoint were shown in both groups. Although there was no significant difference in PANSS scores and weight-related parameters between the two groups through the whole 13-week study. The increased level of triglyceride and HOMA-IR at endpoint from baseline in the olanzapine group was higher than the PP group. There was a stronger elevation of prolactin level in the PP group.. In summary, PP and olanzapine showed similar improvement in the treatment of FES patients. This study also reinforced the necessity for regular monitoring of metabolic parameters in schizophrenia patients prescribed atypical antipsychotics. Clinical trial registration numbers: ChiCTR-IOR-14005304. Date of registration: 2014-10-11.

Topics: Acute Disease; Adipose Tissue; Administration, Oral; Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Body Weight; Female; Humans; Injections; Lipids; Male; Olanzapine; Paliperidone Palmitate; Prolactin; Psychiatric Status Rating Scales; Schizophrenia; Treatment Outcome; Waist Circumference; Young Adult

We aim to determine the most efficacious of 3 common medication regimens for the sedation of acutely agitated emergency department (ED) patients.. We undertook a randomized, controlled, double-blind, triple-dummy, clinical trial in 2 metropolitan EDs between October 2014 and August 2015. Patients aged 18 to 65 years and requiring intravenous medication sedation for acute agitation were enrolled and randomized to an intravenous bolus of midazolam 5 mg-droperidol 5 mg, droperidol 10 mg, or olanzapine 10 mg. Two additional doses were administered, if required: midazolam 5 mg, droperidol 5 mg, or olanzapine 5 mg. The primary outcome was the proportion of patients adequately sedated at 10 minutes.. Three hundred forty-nine patients were randomized to the 3 groups. Baseline characteristics were similar across the groups. Ten minutes after the first dose, significantly more patients in the midazolam-droperidol group were adequately sedated compared with the droperidol and olanzapine groups: differences in proportions 25.0% (95% confidence interval [CI] 12.0% to 38.1%) and 25.4% (95% CI 12.7% to 38.3%), respectively. For times to sedation, the differences in medians between the midazolam-droperidol group and the droperidol and olanzapine groups were 6 (95% CI 3 to 8) and 6 (95% CI 3 to 7) minutes, respectively. Patients in the midazolam-droperidol group required fewer additional doses or alternative drugs to achieve adequate sedation. The 3 groups' adverse event rates and lengths of stay did not differ.. Midazolam-droperidol combination therapy is superior, in the doses studied, to either droperidol or olanzapine monotherapy for intravenous sedation of the acutely agitated ED patient.

Topics: Acute Disease; Adult; Benzodiazepines; Conscious Sedation; Double-Blind Method; Droperidol; Drug Therapy, Combination; Emergency Service, Hospital; Female; Humans; Hypnotics and Sedatives; Injections, Intravenous; Male; Midazolam; Olanzapine; Psychomotor Agitation

To examine the efficacy and safety of (1) midazolam-droperidol versus droperidol and (2) midazolam-droperidol versus olanzapine for methamphetamine-related acute agitation.. A multi-centre, randomized, double-blind, controlled, clinical trial was conducted in two Australian emergency departments, between October 2014 and September 2015.. Three hundred and sixty-one patients, aged 18-65 years, requiring intravenous medication sedation for acute agitation, were enrolled into this study. We report the results of a subgroup of 92 methamphetamine-affected patients.. Patients were assigned randomly to receive either an intravenous bolus of midazolam 5 mg-droperidol 5 mg combined, droperidol 10 mg or olanzapine 10 mg. Two additional doses were administered, if required: midazolam 5 mg, droperidol 5 mg or olanzapine 5 mg, respectively.. The primary outcome was the proportion of patients sedated adequately at 10 minutes. Odds ratios with 95% confidence intervals (ORs, 95% CI) were estimated.. The baseline characteristics of patients in the three groups were similar. At 10 minutes, significantly more patients in the midazolam-droperidol group [29 of 34 (85.3%)] were sedated adequately compared with the droperidol group [14 of 30 (46.7%), OR = 6.63, 95% CI = 2.02-21.78] or with the olanzapine group [14 of 28 (50.0%), OR 5.80, 95% CI = 1.74-19.33]. The number of patients who experienced an adverse event (AE) in the midazolam-droperidol, droperidol and olanzapine groups was seven of 34, two of 30 and six of 28, respectively. The most common AE was oxygen desaturation.. A midazolam-droperidol combination appears to provide more rapid sedation of patients with methamphetamine-related acute agitation than droperidol or olanzapine alone.

Topics: Acute Disease; Adolescent; Adult; Aged; Akathisia, Drug-Induced; Australia; Benzodiazepines; Dopamine D2 Receptor Antagonists; Double-Blind Method; Droperidol; Drug Therapy, Combination; Female; Humans; Hypnotics and Sedatives; Injections, Intravenous; Male; Methamphetamine; Midazolam; Middle Aged; Olanzapine; Selective Serotonin Reuptake Inhibitors; Treatment Outcome; Young Adult

This retrospective review provides preliminary data regarding the safety and efficacy of olanzapine for chemotherapy-induced vomiting (CIV) control in children.. Children <18 years old who received olanzapine for acute chemotherapy-induced nausea and vomiting (CINV) control from December 2010 to August 2013 at four institutions were identified. Patient characteristics, chemotherapy, antiemetic prophylaxis, olanzapine dosing, CIV control, liver function test results and adverse events were abstracted from the health record. Toxicity was graded using CTCAEv4.03.. Sixty children (median age 13.2 years; range: 3.10-17.96) received olanzapine during 158 chemotherapy blocks. Olanzapine was most often (59%) initiated due to a history of poorly controlled CINV. The mean initial olanzapine dose was 0.1 mg/kg/dose (range: 0.026-0.256). Most children who received olanzapine beginning on the first day of the chemotherapy block experienced complete CIV control throughout the acute phase (83/128; 65%). There was no association between the olanzapine dose/kg and complete CIV control (OR 1.01; 95% CI: 0.999-1.020; P = 0.091). Sedation was reported in 7% of chemotherapy blocks and was significantly associated with increasing olanzapine dose (OR: 1.17; 95% CI: 1.08-1.27; P = 0.0001). Of the 25 chemotherapy blocks where ALT and/or AST were reported more than once, grade 1-3 elevations were observed in five. The mean weight change in 31 children who received olanzapine during more than one chemotherapy block was 0% (range: -22 to +18).. Olanzapine may be an important option to improve CIV control in children. Prospective controlled evaluation of olanzapine for CINV prophylaxis in children is warranted.

Topics: Acute Disease; Adolescent; Antiemetics; Antineoplastic Agents; Benzodiazepines; Child; Child, Preschool; Female; Humans; Male; Neoplasms; Olanzapine; Retrospective Studies; Vomiting

This study was a comparative investigation of the clinical efficacy and safety of intramuscular (IM) olanzapine, IM haloperidol, and IM levomepromazine in acute agitated patients with schizophrenia.. The subjects were 122 inpatients. Their clinical symptoms were assessed using Positive and Negative Syndrome Scale Excited Component (PANSS-EC), PANSS, and Agitation-Calmness Evaluation Scale, and their safety were assessed using the Abnormal Involuntary Movement Scale, Barnes Akathisia Rating Scale (BARS), and Drug-induced Extrapyramidal Symptoms Scale (DIEPSS).. The mean changes from baseline on the PANSS-EC, Agitation-Calmness Evaluation Scale, Abnormal Involuntary Movement Scale, BARS, and DIEPSS scores were significantly better in both IM olanzapine and IM levomepromazine than in IM haloperidol. Of these, the mean changes from baseline on the BARS and DIEPSS scores were significantly better in IM olanzapine than in IM levomepromazine. The mean change from baseline on the PANSS positive score was significantly better in both IM olanzapine and IM haloperidol than in IM levomepromazine.. The results of this study suggest the possibility that the anti-agitation effects of IM olanzapine and IM levomepromazine are more rapid than those of IM haloperidol. No worsening of EPS was observed. Our results also suggest that compared with IM levomepromazine, IM olanzapine is safer and affords greater improvement in symptoms.

Topics: Acute Disease; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Female; Haloperidol; Humans; Injections, Intramuscular; Male; Methotrimeprazine; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Psychomotor Agitation; Schizophrenia; Treatment Outcome

Studies of intramuscular (IM) olanzapine in Asian and Taiwanese populations are limited. This study examined the efficacy and safety of IM olanzapine in Taiwanese patients with schizophrenia and acute agitated behavior.This was a multicenter, double-blind, randomized, parallel study comparing the efficacy and safety of 10 mg/d IM olanzapine (n = 25) against 7.5 mg/d haloperidol (n = 24). The primary objective was to assess the change of agitation from baseline to 2 hours after the first IM injection on the Positive and Negative Symptom Scale-Excited Component Scale.The changes of Positive and Negative Symptom Scale-Excited Component Scale score from baseline to 2 hours after the first IM injection did not show statistically significant difference between study groups (olanzapine -9.0 ± 5.7, haloperidol -7.9 ± 4.0, P = 0.254). Both groups reported insomnia as the most common treatment-emergent adverse event, and no serious adverse event was reported.Intramuscular olanzapine and IM haloperidol are similarly effective antipsychotic agents in treating agitated symptoms in Taiwanese patients with schizophrenia. Both IM olanzapine and IM haloperidol were proven to be safe and well tolerated, which also provided alternative options in the treatment of patients with schizophrenia with agitation.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Female; Haloperidol; Humans; Injections, Intramuscular; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Psychomotor Agitation; Schizophrenia; Taiwan; Treatment Outcome

We examined whether augmentation with olanzapine would be superior to switching to olanzapine among early non-responders (ENRs) to risperidone, and whether augmentation with risperidone would be superior to switching to risperidone among ENRs to olanzapine. We performed a rater-blinded, randomized clinical trial at psychiatric emergency sites. Eligible patients were newly admitted patients with acute schizophrenia. ENRs to the initial antipsychotic (Clinical Global Impressions-Improvement Scale: ≥ 4 at 2 weeks) were allocated to receive either augmentation with or switching to the other antipsychotic (RIS+OLZ vs. RIS-OLZ; OLZ+RIS vs.. Sixty patients who completed 2 weeks of risperidone treatment were divided into 33 early responders (RIS-ER) and 27 ENRs (RIS+OLZ, n=14; RIS-OLZ, n=13). Although time to treatment discontinuation for any cause was significantly shorter in RIS+OLZ group (54.1 days [95% confidence interval, 41.3-67.0]) than in RIS-ER group (68.7 [61.2-76.2]; P=0.050), it was not significantly shorter in RIS-OLZ group (58.5 [43.1-73.9]) than in RIS-ER group (P=0.19). Sixty patients who completed 2 weeks of olanzapine treatment were divided into 36 early responders (OLZ-ER) and 24 ENRs (OLZ+RIS, n=11; OLZ-RIS, n=13). Although time to treatment discontinuation for any cause was significantly shorter in OLZ-RIS group (56.1days [40.7-71.5]) than in OLZ-ER group (74.9 [68.5-81.3]; P=0.008), it was not significantly shorter in OLZ+RIS group (64.6 [49.6-79.6]) than in OLZ-ER group (P=0.20).. Despite the lack of pharmacokinetic investigation of dose adequacy in this study, it is possible that switching to olanzapine among ENRs to risperidone might have a small advantage over augmentation with olanzapine, while augmentation with risperidone might have a small advantage over switching to risperidone among ENRs to olanzapine. Further research is required before it would be appropriate to modify routine practice in the direction of these findings.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Drug Substitution; Drug Therapy, Combination; Female; Humans; Japan; Kaplan-Meier Estimate; Male; Middle Aged; Olanzapine; Prospective Studies; Psychiatric Status Rating Scales; Risperidone; Schizophrenia; Single-Blind Method; Time Factors; Treatment Outcome

We examined clinical characteristics including serum olanzapine concentrations for acute schizophrenia patients who required above conventional doses. We performed a rater-blinded, randomized clinical trial in 12 psychiatric emergency sites. Eligible patients were 18-64 years old and met diagnostic criteria for schizophrenia, acute schizophrenia-like psychotic disorder, or schizoaffective disorder. A total of 42 patients were randomly assigned by means of sealed envelopes to receive risperidone (3-12 mg/day; n=20) and olanzapine (10-40 mg/day; n=22), with follow-up at 8 weeks. The Negative score of the Positive and Negative Syndrome Scale was significantly higher in patients who required high doses than in patients who responded to conventional doses. Serum olanzapine concentrations at the time of oral 20mg/day could be obtained from 5 out of 7 patients who subsequently required high-dose olanzapine. All values were more than 30 ng/mL after 11-16 h from dosing to sample collection, and the mean value was 47.876 (S.D. 21.546) ng/mL. Such concentrations are appropriate with respect to a therapeutic range of 20-50 ng/mL. The present study has shown evidence that the reason for requiring high-dose olanzapine cannot be explained by pharmacokinetics in the treatment of acute-phase schizophrenia.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Diagnostic and Statistical Manual of Mental Disorders; Dose-Response Relationship, Drug; Emergency Services, Psychiatric; Female; Follow-Up Studies; Humans; Male; Middle Aged; Olanzapine; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology; Young Adult

Parenteral benzodiazepines or antipsychotics are often used to manage acute agitation in emergency department (ED) settings in which alternative strategies have failed or are not feasible. There are scant data comparing parenteral medication regimens. We aim to determine the efficacy and safety of intravenous droperidol or olanzapine as an adjunct to intravenous midazolam for rapid patient sedation.. We undertook a randomized, double-blind, placebo-controlled, double-dummy, clinical trial in 3 EDs (August 2009 to March 2011). Adult patients (n=336) requiring intravenous drug sedation for acute agitation were randomized to receive a saline solution (control), droperidol (5 mg), or olanzapine (5 mg) bolus. This was immediately followed by incremental intravenous midazolam boluses (2.5 to 5 mg) until sedation was achieved. The primary outcome was time to sedation. Secondary outcomes were need for "rescue" drugs and adverse events.. Three hundred thirty-six patients were randomized to the 3 groups. Baseline characteristics were similar across groups. The differences in medians for times to sedation between the control and droperidol and control and olanzapine groups were 4 minutes (95% confidence interval [CI] 1 to 6 minutes) and 5 minutes (95% CI 1 to 6 minutes), respectively. At any point, patients in the droperidol and olanzapine groups were approximately 1.6 times more likely to be sedated compared with controls: droperidol and olanzapine group hazard ratios were 1.61 (95% CI 1.23 to 2.11) and 1.66 (95% CI 1.27 to 2.17), respectively. Patients in the droperidol and olanzapine groups required less rescue or alternative drug use after initial sedation. The 3 groups' adverse event profiles and lengths of stay did not differ.. Intravenous droperidol or olanzapine as an adjunct to midazolam is effective and decreases the time to adequate sedation compared with midazolam alone.

Topics: Acute Disease; Adolescent; Adult; Aged; Benzodiazepines; Double-Blind Method; Droperidol; Drug Therapy, Combination; Emergency Service, Hospital; Female; Humans; Hypnotics and Sedatives; Injections, Intravenous; Intention to Treat Analysis; Kaplan-Meier Estimate; Male; Midazolam; Middle Aged; Olanzapine; Proportional Hazards Models; Psychomotor Agitation; Time Factors; Treatment Outcome; Young Adult

To assess the effects of olanzapine long-acting injection (olanzapine-LAI) on levels of functioning in acutely ill patients with schizophrenia.. During this 8-week randomized, double-blind, placebo-controlled trial, 404 inpatients were randomized to four treatment arms (olanzapine-LAI 210 mg/2 weeks = 106; olanzapine-LAI 300 mg/2 weeks = 100; olanzapine-LAI 405 mg/4 weeks = 100; placebo = 98). Also, data from the three active dosing arms were combined and compared to placebo data.. NCT00088478.. The treatment group comparison of mean change from baseline to endpoint in the total score and four subdomains of the Heinrichs-Carpenter Quality of Life Scale (QLS) and in the 2 summary scores and 8 subscale scores of the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) were assessed using an ANOVA model.. All three olanzapine-LAI treatment groups and the combined olanzapine-LAI group were superior to placebo on the QLS total score (all p-values < 0.01) and the Intrapsychic Foundations subdomain (all p-values < 0.02). Olanzapine-LAI 210 mg/2 weeks (p < 0.001), 300 mg/2 weeks (p = 0.006), and the combined olanzapine-LAI group (p = 0.003) were superior to placebo on the Interpersonal Relations subdomain. The 300 mg/2 weeks group (p = 0.027) and the combined olanzapine-LAI group (p = 0.014) were also superior to placebo on the Instrumental Role subdomain. For the SF-36, the 300 mg/2 weeks and 405 mg/4 weeks olanzapine-LAI groups and the combined olanzapine-LAI group were superior to placebo on the Mental component score (all p-values < 0.05). Each olanzapine-LAI group and the combined group were superior on the Mental Health scale (all p-values < 0.05). Significant negative correlations between PANSS scores and measures of functioning indicate that as symptoms decreased, functioning increased.. These results suggest that olanzapine-LAI may improve level of functioning in acutely ill patients with schizophrenia within 8 weeks of initiating treatment.

Topics: Acute Disease; Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Female; Humans; Injections; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Schizophrenia; Treatment Outcome; Young Adult

Paliperidone ER monotherapy was efficacious in treating acute mania in two 3-week studies in patients with bipolar I disorder. We assessed its efficacy in a study investigating maintenance treatment of clinically stable patients with this disorder.. Patients (n=766), aged 18 to 65 years inclusive, with current manic or mixed episodes were initially randomized (4:1) to flexibly-dosed paliperidone ER (3-12 mg/day) or olanzapine (5-20 mg/day; 3-week acute treatment phase); responders continued the same treatment (12-week continuation phase). Patients on paliperidone ER who achieved remission during this phase were randomized (1:1) to fixed-dose paliperidone ER (n=152) or placebo (n=148); those on olanzapine continued to receive that at fixed dose (n=83) (maintenance phase).. Median time to recurrence of any mood symptoms (primary endpoint) was: 558 days (paliperidone ER), 283 days (placebo) and not observed with olanzapine (<50% of patients experienced recurrence). Time to recurrence of any mood symptoms was significantly longer with paliperidone ER than placebo (p=0.017; based on weighted Z-test at 0.0198 significance level; hazard ratio [placebo: paliperidone ER; unweighted 95% confidence interval]: 1.43 [1.03; 1.98]); the difference was significant for preventing recurrence of manic, but not depressive, symptoms. Treatment-emergent adverse events (maintenance phase) occurred more often in olanzapine group (64%) than placebo (59%) or paliperidone ER groups (55%).. Responder-enriched design prevents extrapolation of data to patients not previously stabilized on paliperidone ER.. Paliperidone ER significantly delayed the time to recurrence of any mood symptoms, versus placebo, in patients with bipolar I disorder. No new safety concerns emerged.

Topics: Acute Disease; Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Isoxazoles; Male; Middle Aged; Olanzapine; Paliperidone Palmitate; Pyrimidines; Secondary Prevention; Young Adult

JNJ-37822681 is a novel, highly selective dopamine D₂ receptor antagonist characterized by a rapid dissociation rate from the dopamine D₂ receptor. This profile was hypothesized to confer antipsychotic efficacy and improved tolerability. In this 12-week study, the efficacy and safety of JNJ-37822681 were evaluated in patients with an acute exacerbation of schizophrenia, randomly assigned (1:1:1:1:1) to JNJ-37822681 (10-, 20- or 30-mg bid), olanzapine (15 mg once-daily), or placebo (for 6 weeks followed by olanzapine for 6 weeks). Of 498 randomized patients, 298 (60%) completed the study. All JNJ-37822681 dose groups and the olanzapine group showed significantly greater reduction in PANSS total score from baseline to week 6 versus placebo (all p-values < 0.001). Least-squares adjusted mean changes from baseline to week 6 in PANSS total score were: -6.4 (placebo); -18.4 (10 mg JNJ-37822681), -17.7 (20 mg JNJ-37822681), -20.0 (30 mg JNJ-37822681) and -22.9 (olanzapine). All JNJ-37822681 groups showed significant improvement versus placebo from baseline to week 6 in the PANSS subscales, Marder factors, Clinical Global Impression of Severity, and in the Subjective Well-Being on Neuroleptics scale (all p-values < 0.05). The most common treatment-emergent adverse events with JNJ-37822681 were insomnia (17%) and akathisia (13%). Incidences of extrapyramidal symptoms were dose-related and were comparable for JNJ-37822681 10 mg bid and olanzapine groups. All JNJ-37822681 dose groups showed lesser weight gain compared with olanzapine. The efficacy and tolerability profile of the JNJ-37822681 10 mg bid was consistent with the study hypothesis.

Topics: Acute Disease; Adult; Akathisia, Drug-Induced; Antipsychotic Agents; Benzodiazepines; Diagnostic and Statistical Manual of Mental Disorders; Dopamine Antagonists; Dopamine D2 Receptor Antagonists; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Incidence; Intention to Treat Analysis; Male; Middle Aged; Olanzapine; Patient Dropouts; Piperidines; Psychiatric Status Rating Scales; Pyridazines; Receptors, Dopamine D2; Schizophrenia; Schizophrenic Psychology; Sleep Initiation and Maintenance Disorders

The study was designed to evaluate the short-term efficacy and safety of lurasidone in the treatment of acute schizophrenia.. Participants, who were recently admitted inpatients with schizophrenia with an acute exacerbation of psychotic symptoms, were randomly assigned to 6 weeks of double-blind treatment with 40 mg of lurasidone, 120 mg of lurasidone, 15 mg of olanzapine (included to test for assay sensitivity), or placebo, dosed once daily. Efficacy was evaluated using a mixed-model repeated-measures analysis of the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score (as the primary efficacy measure) and Clinical Global Impressions severity (CGI-S) score (as the key secondary efficacy measure).. Treatment with both doses of lurasidone or with olanzapine was associated with significantly greater improvement at week 6 on PANSS total score, PANSS positive and negative subscale scores, and CGI-S score compared with placebo. There was no statistically significant difference in mean PANSS total or CGI-S change scores for the lurasidone groups compared with the olanzapine group. With responders defined as those with an improvement of at least 20% on the PANSS, endpoint responder rates were significant compared with placebo for olanzapine only. The incidence of akathisia was higher with 120 mg of lurasidone (22.9%) than with 40 mg of lurasidone (11.8%), olanzapine (7.4%), or placebo (0.9%). The proportion of patients experiencing ≥ 7% weight gain was 5.9% for the lurasidone groups combined, 34.4% for the olanzapine group, and 7.0% for the placebo group.. Lurasidone was an effective treatment for patients with acute schizophrenia. Safety assessments indicated a higher frequency of adverse events associated with 120 mg/day of lurasidone compared with 40 mg/day.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Isoindoles; Lurasidone Hydrochloride; Male; Middle Aged; Olanzapine; Patient Admission; Psychiatric Status Rating Scales; Schizophrenia; Thiazoles; Treatment Outcome

Among the available mood stabilizers, it appears that lithium may share an important role for treatment of acute mania. In a study from Sep. 2007 to Apr. 2008 at Razi Psychiatric Hospital we evaluated the efficiency of olanzapine vs. lithium.. Forty (40) female inpatients meeting DSM-IV-TR criteria for acute mania were entered into a 3-week parallel group, double-blind study for random assignment to olanzapine or lithium carbonate in a 1:1 ratio. Primary outcome measurements were the changes in Manic State Rating Scale (MSRS) at baseline and weekly intervals up to the third week. Similarly, overall illness severity was rated using the Clinical Global Impression-Severity of illness scale (CGI-S) at baseline and at the end of the third week. Analysis of the data was accomplished by means of split-plot (mixed) and repeated measures analysis of variance (ANOVA) and t test.. While both olanzapine and lithium were found to be significantly helpful in the improvement of manic symptoms (p<0.05), lithium was considerably more successful by the end of the third week (p<0.0002 and p<0.003, for frequency and intensity of the symptoms). CGI-S also showed important improvements with both olanzapine and lithium (p<0.043 and p<0.015 for olanzapine and lithium).. Though both olanzapine and lithium were effective in the improvement of manic symptoms, lithium was more beneficial.

Topics: Acute Disease; Adult; Antimanic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Female; Humans; Inpatients; Lithium Carbonate; Olanzapine; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index; Treatment Outcome

Asenapine is indicated in adults for acute treatment of manic or mixed episodes associated with bipolar I disorder with or without psychotic features. This randomized, double-blind, placebo-controlled trial assessed the efficacy, safety, and tolerability of asenapine in bipolar I disorder.. Adults experiencing manic or mixed episodes were randomized to 3 weeks of flexible-dose treatment with sublingual asenapine (day 1: 10mg BID, 5 or 10mg BID thereafter; n=185), placebo (n=98), or oral olanzapine (day 1: 15 mg QD, 5-20mg QD thereafter; n=205). Primary efficacy, YMRS total score change from baseline to day 21, was assessed using ANCOVA with last observation carried forward.. Mean daily doses were 18.4 mg asenapine and 15.9mg olanzapine. Least squares mean changes in YMRS total score on day 21 were significantly greater with asenapine than placebo (-11.5 vs -7.8; P<0.007), with advantage seen as early as day 2 (-3.2 vs -1.7; P=0.022). Changes with olanzapine on days 2 and 21 also exceeded placebo (both P<0.0001). YMRS response and remission rates with olanzapine, but not asenapine, exceeded those of placebo. Incidence of EPS-related adverse events was 10.3%, 3.1%, and 6.8% with asenapine, placebo, and olanzapine, respectively; incidence of clinically significant weight gain (7.2%; 1.2%; 19.0%). Mean weight change (baseline to endpoint) was 0.9, 0.1, and 2.6 kg with asenapine, placebo, and olanzapine, respectively.. As this short-term study was designed for comparisons with placebo, any comparisons between asenapine and olanzapine should be interpreted cautiously.. Asenapine was superior to placebo in reducing YMRS total score and was well tolerated.

Topics: Acute Disease; Administration, Sublingual; Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzocycloheptenes; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Heterocyclic Compounds, 4 or More Rings; Humans; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Psychometrics; Young Adult

The purpose of this study was to compare efficacy and safety among intramuscular olanzapine, intramuscular haloperidol, orally disintegrating olanzapine tablets, and oral risperidone solution for agitated patients with psychosis during the first 24 hours of treatment in an acute care psychiatric ward.. Forty-two inpatients from an acute care psychiatric ward of a medical center in central Taiwan were enrolled. They were randomly assigned to 1 of the 4 treatment groups (10-mg intramuscular olanzapine, 10-mg olanzapine oral disintegrating tablet, 3-mg oral risperidone solution, or 7.5-mg intramuscular haloperidol). Agitation was measured by using the excited component of the Positive and Negative Syndrome Scale (PANSS-EC), the Agitation-Calmness Evaluation Scale, and the Clinical Global Impression--Severity Scale during the first 24 hours.. There were significant differences in the PANSS-EC total scores for the 4 intervention groups at 15, 30, 45, 60, 75, and 90 minutes after the initiation of treatment. More significant differences were found early in the treatment. In the post hoc analysis, the patients who received intramuscular olanzapine or orally disintegrating olanzapine tablets showed significantly greater improvement in PANSS-EC scores than did patients who received intramuscular haloperidol at points 15, 30, 45, 60, 75, and 90 minutes after injection.. These findings suggest that intramuscular olanzapine, orally disintegrating olanzapine tablets, and oral risperidone solution are as effective treatments as intramuscular haloperidol for patients with acute agitation. Intramuscular olanzapine and disintegrating olanzapine tablets are more effective than intramuscular haloperidol in the early phase of the intervention. There is no significant difference in effectiveness among intramuscular olanzapine, orally disintegrating olanzapine tablets, and oral risperidone solution.

Topics: Acute Disease; Administration, Oral; Adult; Benzodiazepines; Disease Management; Female; Haloperidol; Humans; Injections, Intramuscular; Male; Middle Aged; Olanzapine; Pharmaceutical Solutions; Prospective Studies; Psychiatric Department, Hospital; Psychiatric Status Rating Scales; Psychomotor Agitation; Psychotic Disorders; Risperidone; Solubility; Tablets; Taiwan; Treatment Outcome

To enhance functional outcome in schizophrenia improvement of cognitive symptoms is crucial.. Using a comprehensive test battery, this follow-up examines cognitive effects in patients with recent-onset schizophrenia after a change of medication following insufficient clinical response and intolerance.. After eight weeks cognitive outcomes had not improved in the patients having switched from olanzapine to ziprasidone (n=11; mean dose 136 mg) nor in those having switched from ziprasidone to olanzapine (n=10; mean 16 mg), while the symptoms of patients maintaining olanzapine (n=18; mean 10.9 mg) or ziprasidone (n=18; mean 88.9 mg) treatment had not improved further.. The findings suggest that also in early-stage schizophrenia the antipsychotics tested affect cognitive symptoms similarly.

Topics: Acute Disease; Adolescent; Adult; Benzodiazepines; Cognition; Cross-Over Studies; Double-Blind Method; Drug Substitution; Female; Follow-Up Studies; Humans; Male; Neuropsychological Tests; Olanzapine; Piperazines; Schizophrenia; Schizophrenic Psychology; Thiazoles; Treatment Outcome; Young Adult

An open-label study was performed to investigate the clinical efficacy and tolerability of olanzapine orally disintegrating tablets (Zyprexa Zydis) in ameliorating excitement symptoms in the acute phase of schizophrenia. Fifty-three patients meeting DSM-IV criteria for first-episode schizophrenia and treated with olanzapine monotherapy were evaluated with regard to their clinical improvement, behavioural response to medication, and extrapyramidal side effects using the Positive and Negative Syndrome Scale Excited Component (PANSS-EC), Nursing Assessment of Medication Acceptance (NAMA), and Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS), respectively. Scores of PANSS-EC were significantly reduced after 3 days of olanzapine administration. A reduction in NAMA scores was also observed 7 days after administration of olanzapine. The DIEPSS score was unaffected by olanzapine administration. These results suggest that olanzapine orally disintegrating tablets are effective and well-tolerated for treatment excitement in the acute phase of schizophrenic patients. In addition, it is possible that adherence to medications is improved by using olanzapine orally disintegrating tablets.

Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Diagnostic and Statistical Manual of Mental Disorders; Female; Humans; Male; Middle Aged; Mouth; Olanzapine; Patient Compliance; Prospective Studies; Psychomotor Agitation; Schizophrenia; Severity of Illness Index; Solubility; Young Adult

To assess the efficacy and tolerability of asenapine versus olanzapine in the extended treatment of bipolar mania.. Patients with bipolar I disorder experiencing acute manic or mixed episodes who completed either of two 3-week, double-blind trials with asenapine 5 or 10 mg twice daily, olanzapine 5 to 20 mg once daily, or placebo were eligible for this 9-week, double-blind extension study. Patients receiving active medication in the 3-week trials continued the same regimen; those who had received placebo were blindly switched to asenapine but were assessed for safety outcomes only. The primary efficacy measure was the change from baseline to day 84 on the Young Mania Rating Scale (YMRS) total score in the per-protocol population. Results on the primary efficacy outcome were used to determine the noninferiority of asenapine versus olanzapine.. A total of 504 patients (placebo/asenapine, n = 94; asenapine, n = 181; olanzapine, n = 229) were enrolled in the extension study. At day 84, the mean (SD) change from baseline in YMRS total score was -24.4 (8.7) for asenapine and -23.9 (7.9) for olanzapine. Prespecified statistical analysis for noninferiority indicated no significant difference between asenapine and olanzapine. The overall incidence of treatment-emergent adverse events was similar across treatment groups (77% placebo/asenapine, 77% asenapine, 78% olanzapine). Clinically significant weight gain occurred in 10%, 19%, and 31% of the placebo/asenapine, asenapine, and olanzapine groups, respectively.. Asenapine was efficacious, showed noninferiority to olanzapine, and was well tolerated in the extended treatment of patients experiencing manic symptoms associated with bipolar I disorder.

Topics: Acute Disease; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzocycloheptenes; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Heterocyclic Compounds, 4 or More Rings; Humans; International Cooperation; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Severity of Illness Index; Time Factors; Treatment Outcome; Young Adult

Rapid control of agitation is of critical importance in the treatment of acutely ill patients with schizophrenia. Both olanzapine and aripiprazole have been shown to be safe and effective in this setting, with each having somewhat different receptor binding affinity profiles. This 5-day, randomized, double-blind trial evaluated relative improvements in agitation in hospitalized patients who received orally dosed olanzapine (n = 306, 20 mg/d) or aripiprazole (n = 298, 15 mg/d, increasing to 30 mg/d as needed). Lorazepam was also given as needed (total dose, < or =4 mg/d) but not in place of a study drug dose increase. The primary efficacy measure was daily mean change from baseline in Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) score. Secondary measures of positive symptoms and safety were also assessed. Significant improvements from baseline in PANSS-EC and secondary efficacy measures were seen for both olanzapine and aripiprazole (P < 0.001),with no between-group differences. A greater proportion of aripiprazole-treated patients received lorazepam at each visit compared with olanzapine-treated patients, but this difference was significant only at visit 5 (41.2% vs 31.0%, P = 0.033). Fasting glucose and triglycerides increased more significantly in olanzapine-treated patients (P = 0.030 and P < 0.001, respectively). Prolactin increased in the olanzapine group and decreased in the aripiprazole group with a significant between-group difference (P < 0.001). During the first 5 days of randomized treatment, olanzapine and aripiprazole displayed similar efficacy profiles for treating agitation associated with schizophrenia. Aripiprazole-treated patients had smaller increases in glucose and lipids, but no difference was observed between treatments in the proportion of patients experiencing categorical shifts in these measures.

Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Aged; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Blood Glucose; Dopamine Antagonists; Double-Blind Method; Female; Hospitalization; Humans; Lorazepam; Male; Middle Aged; Olanzapine; Piperazines; Prolactin; Psychiatric Status Rating Scales; Psychomotor Agitation; Quinolones; Schizophrenia; Schizophrenic Psychology; Time Factors; Treatment Outcome; Triglycerides; United States; Young Adult

Previous studies have shown that untreated patients with acute schizophrenia present with reduced heart rate variability and complexity as well as increased QT variability. This autonomic dysregulation might contribute to increased cardiac morbidity and mortality in these patients. However, the additional effects of newer antipsychotics on autonomic dysfunction have not been investigated, applying these new cardiac parameters to gain information about the regulation at sinus node level as well as the susceptibility to arrhythmias. We have investigated 15 patients with acute schizophrenia before and after established olanzapine treatment and compared them with matched controls. New nonlinear parameters (approximate entropy, compression entropy, fractal dimension) of heart rate variability and also the QT-variability index were calculated. In accordance with previous results, we have observed reduced complexity of heart rate regulation in untreated patients. Furthermore, the QT-variability index was significantly increased in unmedicated patients, indicating increased repolarization lability. Reduction of the heart rate regulation complexity after olanzapine treatment was seen, as measured by compression entropy of heart rate. No change in QT variability was observed after treatment. This study shows that unmedicated patients with acute schizophrenia experience autonomic dysfunction. Olanzapine treatment seems to have very little additional impact in regard to the QT variability. However, the decrease in heart rate complexity after olanzapine treatment suggests decreased cardiac vagal function, which may increase the risk for cardiac mortality. Further studies are warranted to gain more insight into cardiac regulation in schizophrenia and the effect of novel antipsychotics.

Topics: Acute Disease; Adult; Antipsychotic Agents; Autonomic Nervous System; Benzodiazepines; Case-Control Studies; Female; Heart; Heart Rate; Humans; Male; Olanzapine; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Time Factors; Treatment Outcome; Young Adult

Dissatisfaction with current available heroin detoxification regimens has led to the search for alternatives. Evidences have shown that several neurotransmission systems, including serotonin, are involved in opioid withdrawal. This study investigated the efficacy and tolerability of venlafaxine, a serotonin-norepinephrine reuptake inhibitor, in managing heroin withdrawal symptoms.. This was a randomized, double-blind, and placebo-controlled 7-day trial. Thirty-four heroin-dependent inpatients seeking detoxification were enrolled and assigned to either the venlafaxine (n = 15) or the placebo group (n = 19). The subjects received either venlafaxine 300 mg/d or placebo as their treatment regimen. Outcome measures were Objective Opioid Withdrawal Scale, total sleeping time, visual analog scale for subjective withdrawal severity, Clinical Global Impression scores on discharge, patient's impression of treatment, and amount of ancillary medications used. Data of outcome measures were analyzed by generalized estimating equation model.. We analyzed the data from 20 subjects (8 in venlafaxine group and 12 in placebo group) who remained in the study after the fifth day of the trial. Objective Opioid Withdrawal Scale, visual analog scale, and total sleeping time demonstrated a significant efficacy of venlafaxine compared with the placebo group (P < 0.0001, P = 0.0195, and P < 0.0001, respectively). There was no difference in Clinical Global Impression and patient's impression of treatment between the 2 groups, although the placebo group needed more ancillary medications.. Despite the small sample size, this study showed that venlafaxine is effective in alleviating withdrawal symptoms of heroin with good tolerability and safety.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Capsules; Diagnostic and Statistical Manual of Mental Disorders; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Heroin Dependence; Humans; Male; Olanzapine; Psychiatric Status Rating Scales; Risperidone; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index; Time Factors; Treatment Outcome

There is a dearth of available knowledge relating to the efficacy of switching from one psychotropic agent to another in treating patients with acute mania.. This is a post hoc analysis of data from two randomized, placebo-controlled trials of carbamazepine extended-release capsules (CBZ-ERC) in the treatment of mania, to evaluate the efficacy of CBZ-ERC in patients previously nonresponsive to lithium (n 5 40), olanzapine (n 5 38), or valproate (VPA, n 5 77).. In patients previously on lithium, Young Mania Rating Scale (YMRS) scores improved significantly from baseline to end point (27.4 6 SD 3.5 vs. 15.8 6 11.1; P 5 .0002). In patients previously on VPA or olanzapine, YMRS scores significantly improved in both CBZ-ERC- and placebo-treated groups (VPA: CBZ-ERC, P , .0001; placebo, P 5 .0002; olanzapine: CBZ-ERC, P , .0001; placebo, P 5 .0054). Improvement in YMRS was significantly greater in CBZ-ERC-treated patients versus placebo in subjects previously nonresponsive to lithium (CBZ-ERC 11.6 6 10.3 vs. placebo 4.0 6 11.2, P 5 .03), or VPA (CBZ-ERC 10.8 6 11.9 vs. placebo 5.7 6 9.2; P 5 .04), and trending to be greater for those previously nonresponsive to olanzapine (olanzapine 13.2 6 9.3 vs. placebo 7.3 6 9.7, P 5 .06).. CBZ-ERC is an effective therapy for bipolar patients previously nonresponsive to lithium or valproate. Medication switch is frequently associated with symptom improvement.

Topics: Acute Disease; Adult; Antimanic Agents; Benzodiazepines; Bipolar Disorder; Carbamazepine; Delayed-Action Preparations; Female; Humans; Lithium Compounds; Male; Olanzapine; Valproic Acid

To examine the efficacy and tolerability of a new injectable formulation of olanzapine, olanzapine long-acting injection (LAI), relative to placebo for treatment of acutely ill patients with schizophrenia.. Patients with DSM-IV or DSM-IV-TR schizophrenia in this 8-week, double-blind study were randomly assigned to receive 210 mg/2 weeks, 300 mg/2 weeks, or 405 mg/4 weeks of olanzapine LAI or placebo/2 weeks. No oral antipsychotic supplementation was permitted. The primary efficacy measure was mean baseline-to-end point change in Positive and Negative Syndrome Scale (PANSS) total score. The study was conducted from June 2004 to April 2005.. Mean baseline-to-end point decreases in PANSS total scores were significantly greater for all olanzapine LAI regimens relative to placebo (all p values < .001). The 300 mg/2 weeks and 405 mg/4 weeks olanzapine LAI groups separated from placebo on the PANSS total at 3 days after starting treatment, and all olanzapine LAI groups separated from placebo by 7 days. Rates of clinical improvement (end point Clinical Global Impressions-Improvement scale score or= 7% of baseline (23.6-35.4% vs. 12.4%, p

Topics: Acute Disease; Adolescent; Adult; Aged; Benzodiazepines; Delayed-Action Preparations; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Olanzapine; Schizophrenia

A post hoc analysis of Young Mania Rating Scale (YMRS) item scores was conducted to identify symptoms that may predict impending relapse using prospectively collected data from a double-blind, randomized relapse prevention study of patients treated with olanzapine (N=200, 5-20 mg/d) versus lithium (N=201, 300-1800 mg/d).. Relapses (YMRS > or = 15, or hospitalization) included in this analysis occurred 3-52 weeks after randomization. Repeated measures logistic regression of increases (> or = 1) in YMRS item scores prior to the visit that preceded relapse was used to estimate the odds of relapse.. A total of 31 patients relapsed during the first 3-16 weeks of the study (olanzapine, n=12; lithium, n=19). YMRS items that increased most frequently within a 2-week period preceding relapse were (olanzapine vs. lithium, respectively): increased motor activity/energy (58.3%, 21.1%), irritability (33.3%, 31.6%), decreased need for sleep (25.0%, 10.5%), increased speech (25.0%, 10.5%), and elevated mood (25.0%, 15.8%). YMRS items with significant odds ratios (OR) that predicted relapse in patients treated with olanzapine or lithium, respectively, were: increased motor activity/energy (OR, 35.7; OR, 7.8), irritability (OR, 9.5; OR, 7.8), elevated mood (OR, 8.1; OR, 4.2), and increased sexual interest (OR, 13.7; OR, 7.7).. Early recognition of symptom exacerbation in bipolar mania, particularly increased motor activity-energy may permit clinical interventions to help avert relapse.

Topics: Acute Disease; Adult; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Lithium Carbonate; Male; Middle Aged; Olanzapine; Prognosis; Prospective Studies; Psychiatric Status Rating Scales; Secondary Prevention

Approximately 60% of patients with a first episode of psychosis will significantly reduce the severity of their positive symptomatology with antipsychotic drugs. The aim of this study was to investigate predictors of response to antipsychotic treatment during the first episode of non-affective psychosis. 172 patients (107 male) with a diagnosis of schizophreniform, schizophrenia, schizoaffective, brief reactive psychosis, schizotypal personality disorder or psychosis non-otherwise specified entered the study. Sociodemographic, premorbid and clinical data at baseline were evaluated. Unpaired t-test for continuous and chi2 for categorical data, respectively, were used to compare responders and non-responders selected variables. Multivariate logistic regression was used to establish a prediction model. 57.6% of study subjects (99 of 172) responded to antipsychotic treatment. The following variables were significantly associated with less likelihood of response: 1.--lower severity of general psychopathology, positive symptoms and disorganized symptoms at baseline; 2.--earlier age of onset; 3.--diagnosis of schizophrenia; 4.--longer DUP; 5.--poorer premorbid adjustment during adolescence, and 6.--hospitalization. Multivariate logistic regression demonstrated that differences between responders and non-responders were largely accounted for by BPRS total score, age of onset, premorbid adjustment at early adolescence, and diagnosis. Patients with an early age of onset of schizophrenia, a poor premorbid adolescent functioning, and with a lower severity of psychopathology at intake seem to have a decrease likelihood of responding to antipsychotic treatment. Helping clinicians to identify non-responders is meant as a first step to optimise therapeutic effort to benefit individuals in this vulnerable group.

Topics: Acute Disease; Adolescent; Adult; Age Factors; Antipsychotic Agents; Benzodiazepines; Comorbidity; Female; Haloperidol; Humans; Longitudinal Studies; Male; Middle Aged; Olanzapine; Prognosis; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology; Schizotypal Personality Disorder; Socioeconomic Factors; Spain; Treatment Outcome

Data from a published double-blind randomized trial comparing olanzapine versus haloperidol in acute mania were used to address the response and tolerability of Latin American patients. Primary efficacy end point was the remission rate (Young Mania Rating Scale score

Topics: Acute Disease; Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cholesterol; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Fasting; Female; Haloperidol; Hispanic or Latino; Hospitalization; Humans; Male; Middle Aged; Olanzapine; Remission Induction; Time Factors; Treatment Outcome; Weight Gain; White People

This secondary analysis from a randomized double-blind study of acute bipolar depression compared olanzapine monotherapy, olanzapine-fluoxetine combination (OFC) and placebo in patients with or without comorbid anxiety.. Patients with bipolar disorder and a current depressive episode received olanzapine (5-20 mg/day), OFC (6/25, 6/50, or 12/50 mg/day), or placebo in an 8-week trial. Two populations were defined: comorbid (Hamilton Anxiety Rating Scale, HAM-A > or =18) or non-comorbid (HAM-A <18) anxiety. Changes in Montgomery-Asberg Depression Rating Scale (MADRS) and HAM-A total scores, and rates of response (> or =50% decrease from baseline to endpoint) and remission (MADRS < or =12 or HAM-A < or =7) were analyzed.. Baseline MADRS and YMRS scores were significantly higher in patients with comorbid anxiety relative to those without. Patients without comorbid anxiety were more likely to achieve MADRS response and remission than those with comorbid anxiety (relative risk, RR: 1.21 and 1.29, respectively). Patients with comorbid anxiety had greater rates of response and remission with olanzapine and OFC relative to placebo (response RR:1.45 and 2.14; remission RR:1.96 and 2.32, respectively). Response and remission rates on the HAM-A scale were greater for OFC relative to placebo (RR: 2.00 and 3.20). Weight gain was greater for olanzapine (2.59+/-3.24 kg) and OFC (2.79+/-3.23 kg) relative to placebo, as were baseline to endpoint changes in cholesterol levels (6+/-31 and 10+/-67 mg/dL, respectively).. Comorbid anxiety symptoms in patients with bipolar depression have a negative impact on treatment outcome. Olanzapine and, to a greater extent, olanzapine-fluoxetine combination were effective in reducing both depressive and anxiety symptoms in these patients. The significantly greater changes in weight, glucose and cholesterol parameters observed in the olanzapine and olanzapine-fluoxetine combination groups should be entered into the risk-benefit assessment in determining appropriate treatment options for these patients.

Topics: Acute Disease; Adult; Age of Onset; Antipsychotic Agents; Anxiety Disorders; Benzodiazepines; Bipolar Disorder; Comorbidity; Depression; Double-Blind Method; Female; Humans; Male; Olanzapine; Remission Induction; Severity of Illness Index; Surveys and Questionnaires

Resolution was defined as achieving the severity component of the remission criteria (simultaneous ratings of mild or less on 8 of the PANSS items evaluating the core symptoms of schizophrenia). Analysis of a 6-week open label study with olanzapine 5-20 mg in 306 patients with acute exacerbation, shows resolution to be a clinically meaningful measure and an achievable outcome for treatment of acute psychosis.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Brief Psychiatric Rating Scale; Drug Administration Schedule; Female; Humans; Male; Olanzapine; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Terminology as Topic; Time Factors; Treatment Outcome

Topics: Acute Disease; Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Female; Humans; Male; Middle Aged; Olanzapine; Principal Component Analysis; Schizophrenia; Schizophrenic Psychology; Substance-Related Disorders; Treatment Refusal

Although antipsychotic drugs control acute psychotic manifestations of schizophrenia, improving cognitive symptoms is also important for long-term prognosis.. Three hundred and seventy-seven adult patients with acute psychosis were randomised to either amisulpride (200-800 mg/d) or olanzapine (5-20 mg/d) for 6 months. Neuropsychological performance was assessed at inclusion and after 6 months in a subgroup of 26 subjects (11 treated with amisulpride and 15 with olanzapine) using the Auditory Verbal Learning Test (AVLT), the Trail Making Test (TMT) and the Controlled Oral Word Association Test (COWAT).. The improvement in BPRS score was similar in both treatment groups. No significant differences in test performance between groups were observed at inclusion. After 6 months, AVLT scores increased by 8.7 points in the amisulpride group and by 2.3 points in the olanzapine group (p = 0.049). Completion speed in the TMT increased by 17.4 s (amisulpride) and 15.4 s (olanzapine) for Part A and by 39.8 and 48.8 s, respectively for Part B. Performance in the COWAT improved little in both groups.. Both amisulpride and olanzapine produce sustained improvement in certain measures of neuropsychological performance in patients with schizophrenia; a significant improvement in score on the AVLT was observed only with amisulpride.

Topics: Acute Disease; Adult; Amisulpride; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Olanzapine; Prognosis; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Sulpiride

In a placebo-controlled, double-blind study, the authors investigated the efficacy and safety of olanzapine as monotherapy in relapse prevention in bipolar I disorder.. Patients achieving symptomatic remission from a manic or mixed episode of bipolar I disorder (Young Mania Rating Scale [YMRS] total score < or =12 and 21-item Hamilton Depression Rating Scale [HAM-D] score or =15, HAM-D score > or =15, or hospitalization).. Time to symptomatic relapse into any mood episode was significantly longer among patients receiving olanzapine (a median of 174 days, compared with a median of 22 days in patients receiving placebo). Times to symptomatic relapse into manic, depressive, and mixed episodes were all significantly longer among patients receiving olanzapine than among patients receiving placebo. The relapse rate was significantly lower in the olanzapine group (46.7%) than in the placebo group (80.1%). During olanzapine treatment, the most common emergent event was weight gain; during the open-label phase, patients who received olanzapine gained a mean of 3.1 kg (SD=3.4). In double-blind treatment, placebo patients lost a mean of 2.0 kg (SD=4.4) and patients who continued to take olanzapine gained an additional 1.0 kg (SD=5.2).. Compared to placebo, olanzapine delays relapse into subsequent mood episodes in bipolar I disorder patients who responded to open-label acute treatment with olanzapine for a manic or mixed episode.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Female; Humans; Male; Obesity; Olanzapine; Placebos; Secondary Prevention; Time Factors; Treatment Outcome; Weight Gain

We conducted a naturalistic, multicenter, 24-hour, nonrandomized, observational study describing for the first time the effectiveness and safety of intramuscular (IM) olanzapine to control agitation and aggression in "real world" patients with psychosis. The data thus obtained was compared with that reported from randomized double-blind clinical trials.. 92 patients attending psychiatric emergency settings were enrolled. The study subjects were 44 male and 48 female patients with a mean age of 36.5+/-12 years and DSM-IV-TR diagnoses of schizophrenia (48.9%), psychotic disorder not specified (23.9%) or bipolar disorder (27.2%). 10 mg IM olanzapine was administered to all patients. An optional second injection was permitted> or =2 hours later in line with hospital policy. Evaluations (PANSS-EC and CGI-S) were performed at baseline and 2 and 24 hours following the IM injection.. Two hours after IM olanzapine was administered, a mean decrease of -9.6 in the PANSS-EC from a baseline score of 26.5 was recorded. At the 24-hour endpoint a statistically and clinically significant reduction in the PANSS-EC scores (11.6+/-5.3) was observed as compared with values at study entry (26.5+/-5.9) and at 2 hours endpoint (16.9+/-9.3), which represent a mean decrease of -14.9 and -5.3, respectively.. The present naturalistic study provides naturalistic data on the effectiveness of IM olanzapine in the treatment of acute agitation in patients with schizophrenia or bipolar mania that is in line the data obtained in randomized double-blind clinical trials.

Topics: Acute Disease; Adolescent; Adult; Aged; Aggression; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Olanzapine; Prospective Studies; Psychiatric Status Rating Scales; Psychomotor Agitation; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Time Factors; Treatment Outcome

Randomized controlled drug trials have demonstrated that antipsychotic medication is effective to rapidly improve psychotic symptomatology in first-episode psychosis. However, these results may not be generalizable to routine clinical practice. We evaluated the effectiveness, tolerability, and safety of olanza-pine, risperidone, and haloperidol in individuals with first-episode nonaffective psychosis who are representative of clinical practice and who are treated in routine clinical settings.. 172 patients participated in a practical clinical trial and were randomly assigned to haloperidol (N = 56), risperidone (N = 61), and olanzapine (N = 55). The mean modal daily doses were 5.4 mg/day for halo-peridol, 4 mg/day for risperidone, and 15.3 mg/day for olanzapine; 98.3% of subjects were drug naive at baseline. Data from clinical measures of treatment response and tolerability and safety data from the 6-week acute phase of a large epidemiologic and longitudinal (February 2001 to February 2005) intervention program of first-episode psychosis (schizophrenia spectrum disorders, DSM-IV criteria) are reported.. All 3 treatments showed similar effectiveness in reducing the severity of general, negative, and positive symptomatology after 6 weeks of treatment, as reported by mean change in total Clinical Global Impressions-Severity of Illness scale, Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Positive Symptoms, and Scale for the Assessment of Negative Symptoms scores between baseline and 6 weeks. The proportion of study subjects responding, defined as 40% or greater BPRS total score improvement from baseline, was 57.1% (N = 32 of 56) haloperidol, 52.5% (N = 32 of 61) risperidone, and 63.6% (N = 35 of 55) olanzapine, with no statistical differences among groups. The frequency of extrapyramidal symptoms (chi(2) = 24.519; p < .001) and concomitant anticholinergic medication use (chi(2) = 57.842; p < .0001) was greater with haloperidol than olanzapine or risperidone. Olanzapine-treated patients had significantly more weight gain compared with the haloperidol and risperidone groups (p < .001).. Relatively low doses of haloperidol, risperidone, and olanzapine are equally effective for the acute treatment of first-episode nonaffective psychosis under usual conditions of real clinical practice.

Topics: Acute Disease; Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Brief Psychiatric Rating Scale; Diagnostic and Statistical Manual of Mental Disorders; Drug Administration Schedule; Female; Haloperidol; Humans; Longitudinal Studies; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Treatment Outcome

Weight gain is a common adverse effect associated with olanzapine treatment. Another side effect of olanzapine treatment is a significant increase in circulating leptin levels. This preliminary study monitored the changes in leptin levels for 2 weeks after olanzapine treatment had been initiated. The relationship between the changes in circulating leptin levels and alterations in body weight in 9 patients with schizophrenia who received olanzapine was examined. The results showed that olanzapine may cause a surge in circulating leptin levels before weight gain is manifested. Moreover, higher pretreatment circulating leptin levels predicted lower weight gains after olanzapine treatments (r = -0.93; p < 0.05) after controlling for the effect of sex.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Female; Humans; Leptin; Male; Olanzapine; Schizophrenia; Sex Factors; Weight Gain

This open label study was performed to evaluate the relationship between the plasma concentration of olanzapine and the response in acute schizophrenic inpatients.. A total of 54 inpatients, 38 males and 16 females, age ranging from 18 to 75 years, affected by Schizophrenia (DSM IV criteria) during an exacerbation phase were included in the study. Olanzapine (OLZ) was started at a dose of 5-20 mg/day and was increased to a mean dose of 15.27 mg +/-5.53 S.D. Patients were evaluated at baseline, and after 2 weeks, by using BPRS, PANNS, HRS-D, EPSE, and ACS.. BPRS and total PANSS showed a statistically significant improvement at the end of the study. Olanzapine plasma levels (PL) ranged from 5 to 120 ng/ml (mean 33.15 ng/ml +/- 28.28 S.D.) and showed a positive correlation with OLZ dosage. A significant curvilinear correlation between OLZ PL and clinical improvement (BPRS, PANSS and HRS-D percent of amelioration) was observed.. Olanzapine plasma level determination seems to be a useful tool in optimizing acute treatment particularly for more problematic cases.

Topics: Acute Disease; Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Dose-Response Relationship, Drug; Female; Hospitalization; Humans; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Schizophrenia; Time Factors; Treatment Outcome

Previous research indicated that women are more vulnerable than men to adverse psychological consequences of weight gain. Other research has suggested that weight gain experienced during antipsychotic therapy may also psychologically impact women more negatively. This study assessed the impact of acute treatment-emergent weight gain on clinical and functional outcomes of patients with schizophrenia by patient gender and antipsychotic treatment (olanzapine or haloperidol).. Data were drawn from the acute phase (first 6-weeks) of a double-blind randomized clinical trial of olanzapine versus haloperidol in the treatment of 1296 men and 700 women with schizophrenia-spectrum disorders. The associations between weight change and change in core schizophrenia symptoms, depressive symptoms, and functional status were examined post-hoc for men and women and for each medication group. Core schizophrenia symptoms (positive and negative) were measured with the Brief Psychiatric Rating Scale (BPRS), depressive symptoms with the BPRS Anxiety/Depression Scale and the Montgomery-Asberg Depression Rating Scale, and functional status with the mental and physical component scores on the Medical Outcome Survey-Short Form 36. Statistical analysis included methods that controlled for treatment duration.. Weight gain during 6-week treatment with olanzapine and haloperidol was significantly associated with improvements in core schizophrenia symptoms, depressive symptoms, mental functioning, and physical functioning for men and women alike. The conditional probability of clinical response (20% reduction in core schizophrenia symptom), given a clinically significant weight gain (at least 7% of baseline weight), showed that about half of the patients who lost weight responded to treatment, whereas three-quarters of the patients who had a clinically significant weight gain responded to treatment. The positive associations between therapeutic response and weight gain were similar for the olanzapine and haloperidol treatment groups. Improved outcomes were, however, more pronounced for the olanzapine-treated patients, and more olanzapine-treated patients gained weight.. The findings of significant relationships between treatment-emergent weight gain and improvements in clinical and functional status at 6-weeks suggest that patients who have greater treatment-emergent weight gain are more likely to benefit from treatment with olanzapine or haloperidol regardless of gender.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Female; Haloperidol; Humans; Male; Obesity; Olanzapine; Outcome Assessment, Health Care; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Sex Factors; Treatment Outcome; Weight Gain

It is widely held that there is a delayed onset of antipsychotic action and that any early effects represent nonspecific behavioral effects. Recent research has shown that antipsychotic action begins within the first week. The authors tested the hypothesis that psychosis improves within the first 24 hours of antipsychotic treatment.. In this multicenter, double-blind, placebo-controlled study, 311 patients with a diagnosis of schizophrenia spectrum disorder and an acute exacerbation were randomly assigned to receive 10 mg i.m. of olanzapine, 7.5 mg i.m. of haloperidol, or intramuscular placebo. Subjects were rated with structured rating scales (Positive and Negative Syndrome Scale and Clinical Global Impression) at baseline, 2 hours, and 24 hours.. The olanzapine and haloperidol groups showed greater resolution of overall symptoms than the placebo group; for the olanzapine group, this effect was evident at 2 hours. A factor analysis showed that an independent change in psychosis (which included conceptual disorganization, hallucinatory behavior, unusual thought content) was evident within the first 24 hours for both drugs. This improvement in core psychosis was not mediated unidirectionally by changes in nonspecific behavioral effects or other psychopathology.. These data suggest that the onset of antipsychotic action is early and that the magnitude of this action grows with time. This clinical reality calls into question some prevailing hypotheses regarding the mechanism of action of antipsychotics and suggests that antipsychotic action may be more proximally related to the blockade of dopamine transmission than was originally thought.

Topics: Acute Disease; Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Brief Psychiatric Rating Scale; Dopamine Antagonists; Double-Blind Method; Factor Analysis, Statistical; Haloperidol; Humans; Injections, Intramuscular; Middle Aged; Olanzapine; Placebos; Schizophrenia; Schizophrenic Psychology; Time Factors; Treatment Outcome

This study examined direct treatment costs based on medication and service use data collected in a 47-week multi-center, double-blind, randomized clinical trial of olanzapine versus divalproex for patients with bipolar disorder and and experiencing acute mania.. Patients who completed the 3-week acute phase and entered into the 44-week maintenance phase (n = 147) of the trial were included. Service use data were collected at weeks 3, 7, 15, 23, 31, 39 and 47 of the maintenance phase. Analyses were conducted to address potential biases from discontinuation patterns and use of this patient sub-sample.. Overall, per patient yearly costs were similar for olanzapine- and divalproex-treated patients ($14 967 vs. $15 801). Psychiatric-related costs accounted for 95.4% and 93.6% of the total costs for olanzapine- and divalproextreated patients, respectively. Study medication costs were significantly higher for olanzapine than for divalproex ($4662 vs. $1755, p < 0.01). However, this was offset by the combined effects of numerically lower costs for several other services with olanzapine treatment. Some of the savings associated with olanzapine treatment compared with divalproex treatment resulted from differences in costs associated with emergency room services ($432 vs. $1346, p < 0.05).. Overall per-patient treatment costs were similar for olanzapine and divalproex. Recognizing challenges in analyzing and generalizing cost outcomes from a clinical trial setting, results provide some much-needed comparative economic information regarding these two medication options for treating mania in bipolar disorder.

Topics: Acute Disease; Adult; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cost Savings; Double-Blind Method; Female; Health Care Costs; Health Services; Humans; Male; Middle Aged; Olanzapine; Valproic Acid

Response to typical antipsychotic medication has been associated with achieving a level of striatal dopamine D2 receptor occupancy in the range of 65% to 70%. We undertook this study to determine whether response to the atypical antipsychotic olanzapine occurs at lower levels of D2 receptor occupancy.. Eighteen patients who presented with a first episode of psychosis were randomized to receive olanzapine 5 mg daily or haloperidol 2 mg daily in a double-blind design. We acquired positron emission tomography (PET) scans using the D2 ligand [11C]raclopride within the first 15 days of treatment to determine the percentage of D2 receptors occupied by the medication. According to response, dosage was then adjusted to a maximum dosage of 20 mg daily of either drug. PET scans were repeated after 10 to 12 weeks of treatment.. At the first PET scan, the 8 olanzapine-treated patients had significantly lower D2 receptor occupancies (mean 63.4%, SD 7.3) than those observed in the 10 patients treated with haloperidol (mean 73.0%, SD 6.1). When patients were rescanned following dosage adjustment, mean D2 receptor occupancies were greater than 70% in both groups. D2 receptor occupancies did not differ significantly between the olanzapine-treated group (mean 72.0%, SD 5.7) and the haloperidol-treated group (mean 78.7%, SD 7.6).. These results suggest that, in patients being treated for a first episode of psychosis, olanzapine has its antipsychotic effect at approximately the same levels of D2 receptor occupancy as are achieved with low dosages of haloperidol.

Topics: Acute Disease; Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Corpus Striatum; Dose-Response Relationship, Drug; Double-Blind Method; Female; Haloperidol; Humans; Male; Olanzapine; Positron-Emission Tomography; Psychotic Disorders; Raclopride; Receptors, Dopamine D2; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Risperidone and olanzapine are the 2 most widely prescribed second-generation anti-psychotics. The purpose of this study was to compare the efficacy of risperidone and olanzapine using duration of hospitalization as the primary outcome measure. This outcome was selected as it is an indirect measure of how well patients are responding to the medication and represents a "real world" endpoint relevant to practicing hospital psychiatrists.. The study was done at a large state psychiatric hospital in North Carolina from 2001 to 2003. Subjects were eligible for inclusion if they required treatment with an antipsychotic (e.g., positive symptoms) and were able to provide informed consent. Eighty-five patients entered the study and were randomly assigned to risperidone (N = 40) or olanzapine (N = 45) as their initial antipsychotic. Treatment was naturalistic, and dosing was based on the discretion of the treating physician.. There was no significant difference in the mean durations of hospitalization for the risperidone group (7.9 days) as compared to the olanzapine group (8.1 days). There were no significant differences in the demographics of either treatment group, but, during the study, risperidone-treated patients used more antihistamines (chi(2) = 4.0, p = .05). Eighty percent of each group (N = 36, olanzapine; N = 32, risperidone) remained on the study medication at discharge.. Risperidone and olanzapine were equally efficacious, suggesting that measures other than "efficacy" (e.g., side effects, cost) should be considered when determining overall "effectiveness" of treatment.

Topics: Acute Disease; Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Drug Therapy, Combination; Female; Histamine H1 Antagonists; Hospitalization; Hospitals, Psychiatric; Humans; Length of Stay; Male; Olanzapine; Outcome Assessment, Health Care; Psychotic Disorders; Risperidone; Schizophrenia; Treatment Outcome

Atypical antipsychotics offer advantages over earlier drugs for the treatment of schizophrenia, although few data exist on the relative merits of different atypical antipsychotics. A multicentre, double-blind, randomized trial was performed to compare amisulpride and olanzapine in the treatment of acute schizophrenia. Adult schizophrenic patients with dominant positive symptomatology received amisulpride (200-800 mg/day) or olanzapine (5-20 mg/day) for 6 months. The primary efficacy variable was change from baseline of the Brief Psychiatric Rating Scale (BPRS) score, assessed with a non-inferiority analysis. The evolution of positive and negative symptomatology, depression, social functioning and quality of life were assessed. Safety evaluation included adverse event reporting, neurological status and body weight. The improvement of BPRS score was 32.7% in the amisulpride group and 33.0% in the olanzapine group; thus, the efficacy of amisulpride was not inferior to that of olanzapine. All other secondary efficacy outcome variables evolved to a similar extent in both groups. Adverse event frequency was similar in both groups. Amenorrhoea was encountered only in the amisulpride group (6.2% of patients), whereas elevations of liver transaminases were more frequent in the olanzapine group (17% versus 3.7% of patients). The incidence and mean extent of clinically relevant weight gain were higher in the olanzapine group (35.1% and 3.9 kg) than in the amisulpride group (20.6% and 1.6 kg). The efficacy of amisulpride is not inferior to that of olanzapine in the treatment of acute schizophrenia. The side-effect profile of the two drugs differed.

Topics: Acute Disease; Adolescent; Adult; Aged; Amisulpride; Antipsychotic Agents; Benzodiazepines; Brief Psychiatric Rating Scale; Double-Blind Method; Female; Humans; Male; Middle Aged; Olanzapine; Quality of Life; Schizophrenia; Sulpiride; Treatment Outcome

We conducted a prospective double-blind study of accelerated dose titration of olanzapine in the treatment of newly admitted acutely agitated patients with schizophrenia. Patients were randomized to either oral olanzapine (10 mg per day) or oral haloperidol (10 mg per day), plus lorazepam as needed (up to 12 mg per day). Antipsychotic dosage was increased to 20 mg per day as early as day 3. Patients were evaluated with the Positive and Negative Syndrome Scale (PANSS) Agitation subscale during the first 24 hours of treatment, daily for the first week, then weekly until study completion. Significant within-group improvement was demonstrated in PANSS Agitation scores for both groups as early as 1 hour after initiating therapy (-5.79 +/- 6.30 for olanzapine and -4.89 +/- 6.05 for haloperidol, P <.001). This study demonstrated that accelerated dose titration of oral olanzapine is as efficacious as oral haloperidol in reducing acute agitation in patients with schizophrenia.

Topics: Acute Disease; Administration, Oral; Adult; Anti-Anxiety Agents; Antipsychotic Agents; Benzodiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Emergency Services, Psychiatric; Emergency Treatment; Female; Haloperidol; Humans; Lorazepam; Male; Olanzapine; Prospective Studies; Psychomotor Agitation; Schizophrenia; Severity of Illness Index; Treatment Outcome

The objective of the present study was to compare the efficacy and adverse effects of olanzapine plus fluvoxamine and those of olanzapine alone, in schizophrenic patients with acute exacerbation. A randomized, placebo-controlled, 6-week trial was carried out at a University Hospital in Bangkok, Thailand. The efficacy and adverse effects were assessed biweekly by using the Brief Psychiatric Rating Scale (BPRS) and the Udvalg for Kliniske Undersogelser side-effect scale, respectively. Twenty schizophrenic patients with acute exacerbation were randomly assigned to receive olanzapine plus fluvoxamine or olanzapine alone. The study found that the means of BPRS total and BPRS general psychopathology score changes were significantly larger in olanzapine plus fluvoxamine group (P = 0.037 and P = 0.045, respectively). The incidence of treatment adverse effects is comparable. In conclusion, the study findings suggest that fluvoxamine augmentation to olanzapine is well tolerated and more effective than olanzapine alone for short-term (6-week) treatment of an acute exacerbation of schizophrenia. Due to a number of limitations, further studies are warranted to confirm.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Drug Therapy, Combination; Female; Fluvoxamine; Hospitals, Psychiatric; Humans; Male; Middle Aged; Olanzapine; Prospective Studies; Schizophrenia; Schizophrenic Psychology; Selective Serotonin Reuptake Inhibitors; Thailand; Treatment Outcome

Weight gain is a side effect of therapy with many atypical antipsychotics and may have important clinical repercussions with respect to long-term health and treatment compliance. The primary objective of this double-blind study was to compare the safety and tolerability of aripiprazole and olanzapine in patients with schizophrenia as evidenced by the percentage of patients exhibiting significant weight gain.. This was a 26-week, multicenter, randomized, double-blind, active-controlled trial in patients with DSM-IV schizophrenia who were in acute relapse and required hospitalization. Significant weight gain was defined as a > or = 7% increase in body weight from baseline. Body weight, Positive and Negative Syndrome Scale, and Clinical Global Impressions-Improvement scale (CGI-I) assessments were performed at baseline and at regular intervals during the study. The study period was from April 2000 through June 2001.. 317 patients were randomly assigned to aripiprazole (N = 156) or olanzapine (N = 161). Compared with those treated with aripiprazole, a greater proportion of patients treated with olanzapine exhibited clinically significant weight gain during the trial. By week 26, 37% of olanzapine-treated patients had experienced significant weight gain compared with 14% of aripiprazole-treated patients (p < .001). Statistically significant differences in mean weight change were observed between treatments beginning at week 1 and sustained throughout the study. At week 26, there was a mean weight loss of 1.37 kg (3.04 lb) with aripiprazole compared with a mean increase of 4.23 kg (9.40 lb) with olanzapine among patients who remained on therapy (p < .001). Changes in fasting plasma levels of total cholesterol, high-density lipoprotein cholesterol, and triglycerides were significantly different in the 2 treatment groups, with worsening of the lipid profile among patients treated with olanzapine. There was a consistent and sustained improvement in symptoms in patients who remained on therapy with either olanzapine or aripiprazole as assessed by CGI-I scores and responder rates throughout the study.. Olanzapine had a greater impact on patients' weight than aripiprazole. Significant differences in favor of aripiprazole were also observed in the effects of therapy on plasma lipid profile. Both treatment groups achieved comparable clinically meaningful improvements on efficacy measures. The observed effects on weight and lipids indicate a potentially lower metabolic and cardiovascular risk in patients treated with aripiprazole compared with those treated with olanzapine.

Topics: Acute Disease; Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Double-Blind Method; Female; Humans; Hyperlipidemias; Incidence; Lipids; Male; Obesity; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Quinolones; Schizophrenia; Schizophrenic Psychology; Secondary Prevention; Treatment Outcome; Weight Gain

Elderly psychiatric patients often present with psychotic symptoms that need antipsychotic treatment. Olanzapine is one of the atypical antipsychotics with efficacy for psychotic symptoms and a safer side-effect profile than typical antipsychotics. This study was conducted to assess the efficacy and safety of olanzapine for treatment of geriatric psychosis. The sample population comprised 94 acute-ward patients who were 65 years of age or older. Clinical assessment was conducted at baseline and also at 4 weeks after commencement of olanzapine treatment, with use of the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression Improvement (CGI-I) instruments. A 4-week therapeutic evaluation was completed for 80 patients, 73 of whom (91.3%) experienced mild to substantial improvement as determined from the CGI-I. A mean 52.6% reduction from baseline was also determined from the BPRS. The mean daily dosage of olanzapine in the fourth week was 10.1 +/- 5.3 mg/d (range, 2.5-20.0). Higher olanzapine dosages were administered for patients with functional psychoses than for an analogous group with organic mental disorders. Adverse effects were monitored for all 94 patients, the most common of which were somnolence (18.1%), dizziness (18.1%), and weakness of legs or bradykinesia (16.0%). Body weight and fasting triglyceride and sugar levels were significantly elevated after olanzapine treatment (2.2, 39.9, and 8.9% from baseline, respectively). It seems reasonable to suggest that olanzapine is efficacious for geriatric patients with psychosis and that the dosage should be diagnosis-dependent.

Topics: Acute Disease; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Female; Humans; Male; Olanzapine; Pirenzepine; Prospective Studies; Psychotic Disorders; Treatment Outcome

The role of simple reaction time in schizophrenia has been extensively reported to date in professional literature. However, most studies have examined basic reaction time under static conditions using a single measurement. The aim of the present study was to establish whether any changes occur in simple reaction time during treatment with risperidone or olanzapine in in-patients suffering a relapse of schizophrenia.. Seventeen in-patients suffering acute relapse of schizophrenia (DSM IV criteria) and twenty matched, healthy controls participated in an eight-week, double-blind pilot study. The patients were treated with conventional antipsychotics for seven days after admission and were then randomised to the treatment arms with risperidone (4 mg/day) or with olanzapine (10 mg/day) at a fixed dosage in the first week and thereafter in flexible dosages for the remaining seven weeks. Since no differences were found between reaction times of patients treated with risperidone or olanzapine, the two treatment groups were merged in the statistical analysis before being compared with the normal controls. Psychopathological symptoms were assessed using the Positive and Negative Symptom Scale (PANSS) and extrapyramidal symptoms with the Simpson Angus Scale and Abnormal Involuntary Movement Scale. Reaction time was measured with the Alpha apparatus, connected to a personal computer. All assessments and measurements were conducted four times during the treatment phase of the study.. The reaction time of patients was significantly longer than that of the healthy controls (t1 = 17.11; p1 < 0.05). After eight weeks of treatment the reaction time of patients significantly improved but did not reach that of the healthy controls (t4 = 28.18, p4 < 0.05). Furthermore, the improved reaction time in the patients did not correlate with improvement of psychopathological symptoms or with improved extrapyramidal symptoms.. The results of the study suggest that simple reaction time can improve during treatment with atypical antipsychotics.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Dyskinesia, Drug-Induced; Female; Humans; Male; Neurologic Examination; Neuropsychological Tests; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Reaction Time; Recurrence; Risperidone; Schizophrenia; Schizophrenic Psychology; Slovenia

Divalproex sodium is a mood stabilizer used in the United States for the treatment of acute mania associated with bipolar disorder. Recently, olanzapine, an atypical antipsychotic, was approved for the treatment of acute mania. This study compares the clinical, health-related quality of life (HRQL), and economic outcomes of divalproex and olanzapine in the treatment of acute mania associated with bipolar disorder.. This 12-week, double-blind, double-dummy, randomized clinical trial included 120 subjects with DSM-IV bipolar disorder type I hospitalized for an acute manic episode recruited from 21 U.S. clinical centers. Subjects were randomly assigned to treatment with either divalproex or olanzapine and were followed in hospital for up to 21 days. If after 21 days clinical improvements (based on the Mania Rating Scale [MRS]) were not observed, subjects were discontinued. Subjects showing clinical improvement were treated for up to 12 weeks. HRQL was assessed using the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) after hospital discharge (baseline) and at 6 and 12 weeks. Medical resource use and costs were collected over the 12-week study.. A total of 120 subjects (N = 63 divalproex, N = 57 olanzapine) were randomized, and 78 (65%) were followed beyond 21 days. No statistically significant differences between the treatment groups for baseline-to-endpoint MRS or Q-LES-Q scores were observed. Total 12-week outpatient medical costs were significantly lower for the divalproex-treated group (541 US dollars) compared with the olanzapine-treated group (1080 US dollars) (p =.004). There was no significant difference in total medical costs between the 2 groups (divalproex = 13,703 US dollars; olanzapine = 15,180 US dollars; p =.88).. Divalproex is associated with lower 12-week outpatient costs compared with olanzapine. Divalproex and olanzapine have similar short-term effects on clinical or HRQL outcomes in bipolar disorder subjects.

Topics: Acute Disease; Adult; Ambulatory Care; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Health Care Costs; Health Services; Health Status; Humans; Male; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Quality of Life; Treatment Outcome; Valproic Acid

Few double-blind trials have compared longer-term efficacy and safety of medications for bipolar disorder. The authors report a 47-week comparison of olanzapine and divalproex.. This 47-week, randomized, double-blind study compared flexibly dosed olanzapine (5-20 mg/day) to divalproex (500-2500 mg/day) for manic or mixed episodes of bipolar disorder (N=251). The only other psychoactive medication allowed was lorazepam for agitation. The primary efficacy instrument was the Young Mania Rating Scale; a priori protocol-defined threshold scores were > or =20 for inclusion, < or =12 for remission, and > or = 15 for relapse. Analytical techniques included mixed model repeated-measures analysis of variance for change from baseline, Fisher's exact test (two-tailed) for categorical comparisons, and Kaplan-Meier estimates of time to events of interest.. Over 47 weeks, mean improvement in Young Mania Rating Scale score was significantly greater for the olanzapine group. Median time to symptomatic mania remission was significantly shorter for olanzapine, 14 days, than for divalproex, 62 days. There were no significant differences between treatments in the rates of symptomatic mania remission over the 47 weeks (56.8% and 45.5%, respectively) and subsequent relapse into mania or depression (42.3% and 56.5%). Treatment-emergent adverse events occurring significantly more frequently during olanzapine treatment were somnolence, dry mouth, increased appetite, weight gain, akathisia, and high alanine aminotransferase levels; those for divalproex were nausea and nervousness.. In this 47-week study of acute bipolar mania, symptomatic remission occurred sooner and overall mania improvement was greater for olanzapine than for divalproex, but rates of bipolar relapse did not differ.

Topics: Acute Disease; Adult; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Secondary Prevention; Survival Analysis; Treatment Outcome; Valproic Acid

Two double-blind, placebo-controlled trials of olanzapine in acute mania showed significant overall antimanic efficacy, based on reductions in mania ratings. Their subject-level data were pooled to increase statistical power to test for differences in treatment responses among 10 subgroup pairs of interest using generalized estimating equations methods. Similar drug/placebo superiority and responsiveness to olanzapine was found in men versus women, psychotic versus nonpsychotic subjects, and those presenting in mania versus mixed states, and responses were independent of onset age, current age, or prior illness based on episodes, hospitalizations, recent rapid cycling, lifetime substance use, or previous antipsychotic treatment. Olanzapine and placebo responses paralleled closely (r(s) = 0.73). Patients were relatively more responsive to olanzapine who were younger at illness onset, lacked prior substance abuse, and had not previously received antipsychotic treatment (efficacy ratios 1.5-1.7, all P < 0.01). These well-powered comparisons of subgroups of interest indicate broad efficacy of olanzapine in the treatment of acute mania.

Topics: Acute Disease; Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Female; Humans; Male; Middle Aged; Models, Psychological; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Risk

In the present naturalistic study, the effectiveness and safety of quetiapine, risperidone and olanzapine were compared in the treatment of non selected acutely psychotic patients. It was observed that the rate of antipsychotic switch because of a lack of efficacy or side effects was higher in the quetiapine treated cases in comparison with the risperidone or olanzapine treated cases. The proportion of cases concomitantly treated with typical neuroleptics was significantly higher in the quetiapine group compared with the other two groups. In the outcome of non crossover cases, there were more improvements in the risperidone and olanzapine groups than in the quetiapine group. The results of this study suggest that quetiapine is not as efficacious as risperidone or olanzapine in the emergency psychiatric setting. Due to the methodological limitations of the study, these results must be considered preliminary and need confirmation.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Emergency Services, Psychiatric; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Sampling Studies; Treatment Outcome

Previous studies have examined the safety and tolerability of oral-loaded divalproex sodium in the treatment of acute mania, but not the early efficacy of this dosing strategy. The purpose of this study was to evaluate the early efficacy of oral-loaded divalproex.. In this pooled analysis, 348 subjects from 3 randomized, double-blind, parallel-group, active- or placebo-controlled studies were used to compare the efficacy, safety, and tolerability of oral-loaded divalproex with standard-titration divalproex, lithium, olanzapine, or placebo. Subjects were inpatients diagnosed with acute mania associated with bipolar I disorder (DSM-III-R or -IV and SADS-Change Version). Patients were administered oral-loaded divalproex (20 or 30 mg/kg/day on days 1 and 2 followed by 20 mg/kg/day, and increased at physician's discretion), standard-titration divalproex initiated at 250 mg t.i.d. and titrated to 40-150 microg/mL, lithium (300 mg t.i.d. initial dose) titrated to 0.4 to 1.5 mEq/L, olanzapine (10 mg q.d. initial dose) up to 20 mg/day, or placebo.. The results demonstrate an early efficacy advantage for oral-loaded divalproex compared to standard-titration divalproex at days 5, 7/8, and 10. Efficacy was improved over lithium on day 7/8. There were no efficacy differences between divalproex loading and olanzapine. Divalproex loading showed greater efficacy than placebo at all time points. Divalproex loading was as well tolerated or better tolerated than the other active treatments as measured by adverse events and changes in laboratory parameters.. These results suggest the oral loading of divalproex leads to a more rapid antimanic effect when compared with standard-titration divalproex, lithium, or placebo and is better tolerated than olanzapine and as well tolerated as lithium or standard-titration divalproex.

Topics: Acute Disease; Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Drug Tolerance; Female; Humans; Lithium; Male; Middle Aged; Olanzapine; Pirenzepine; Randomized Controlled Trials as Topic; Severity of Illness Index; Titrimetry; Treatment Outcome; Valproic Acid

This randomized controlled trial compares the efficacy and safety of olanzapine vs haloperidol, as well as the quality of life of patients taking these drugs, in patients with bipolar mania.. The design consisted of 2 successive, 6-week, double-blind periods and compared flexible dosing of olanzapine (5-20 mg/d, n = 234) with haloperidol (3-15 mg/d, n = 219).. Rates of remission (Young-Mania Rating Scale score of < or =12 and 21-item Hamilton Rating Scale for Depression score of < or =8 at week 6) were similar for olanzapine- and haloperidol-treated patients (52.1% vs 46.1%, respectively; P =.15). For the subgroup of patients whose index episode did not include psychotic features, rates of remission were significantly greater for the olanzapine group compared with the haloperidol group (56.7% vs 41.6%, P =.04). Relapse into an affective episode (mania and/or depression) occurred in 13.1% and 14.8% of olanzapine- and haloperidol-treated patients, respectively (P =.56). Switch to depression occurred significantly more rapidly with haloperidol than with olanzapine when using survival analysis techniques (P =.04), and significantly more haloperidol-treated patients experienced worsening of extrapyramidal symptoms, as indicated by several measures. Weight gain was significantly greater in the olanzapine group compared with the haloperidol group (2.82 vs 0.02 kg, P<.001). The olanzapine group had significant improvement in quality of life on several dimensions compared with the haloperidol group.. These data suggest that olanzapine does not differ from haloperidol in achieving overall remission of bipolar mania. However, haloperidol carries a higher rate of extrapyramidal symptoms, whereas olanzapine is associated with weight gain.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Personality Inventory; Pirenzepine; Psychiatric Status Rating Scales; Treatment Outcome

To determine the antipsychotic efficacy and extrapyramidal safety of intramuscular (i.m.) olanzapine and i.m. haloperidol during the first 24 hours of treatment of acute schizophrenia.. Patients (n = 311) with acute schizophrenia were randomly allocated (2:2:1) to receive i.m. olanzapine (10.0 mg, n = 131), i.m. haloperidol (7.5 mg, n = 126), or i.m. placebo (n = 54).. After the first injection, i.m. olanzapine was comparable to i.m. haloperidol and superior to i.m. placebo for reducing mean change scores from baseline on the Brief Psychiatric Rating Scale (BRPS) Positive at 2 hours (-2.9 olanzapine, -2.7 haloperidol, and -1.5 placebo) and 24 hours (-2.8 olanzapine, -3.2 haloperidol, and -1.3 placebo); the BPRS Total at 2 hours (-14.2 olanzapine,-13.1 haloperidol, and -7.1 placebo) and 24 hours (-12.8 olanzapine, -12.9 haloperidol, and -6.2 placebo); and the Clinical Global Impressions (CGI) scale at 24 hours (-0.5 olanzapine, -0.5 haloperidol, and -0.1 placebo). Patients treated with i.m. olanzapine had significantly fewer incidences of treatment-emergent parkinsonism (4.3% olanzapine vs 13.3% haloperidol, P = 0.036), but not akathisia (1.1% olanzapine vs 6.5% haloperidol, P = 0.065), than did patients treated with i.m. haloperidol; they also required significantly less anticholinergic treatment (4.6% olanzapine vs 20.6% haloperidol, P < 0.001). Mean extrapyramidal symptoms (EPS) safety scores improved significantly from baseline during i.m. olanzapine treatment, compared with a general worsening during i.m. haloperidol treatment (Simpson-Angus Scale total score mean change: -0.61 olanzapine vs 0.70 haloperidol; P < 0.001; Barnes Akathisia Scale global score mean change: -0.27 olanzapine vs 0.01 haloperidol; P < 0.05).. I.m. olanzapine was comparable to i.m. haloperidol for reducing the symptoms of acute schizophrenia during the first 24 hours of treatment, the efficacy of both being evident within 2 hours after the first injection. In general, more EPS were observed during treatment with i.m. haloperidol than with i.m. olanzapine.

Topics: Acute Disease; Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Brief Psychiatric Rating Scale; Double-Blind Method; Drug Administration Schedule; Female; Haloperidol; Humans; Injections, Intramuscular; Male; Olanzapine; Schizophrenia; Severity of Illness Index; Time Factors; Treatment Outcome

We aimed to compare clinical outcomes, health-related quality of life (HRQOL) and work status associated with olanzapine and haloperidol treatment in patients with bipolar disorder. This double-blind, randomized controlled trial, comparing flexible dosing of olanzapine (5-20 mg/day, n = 234) to haloperidol (3-15 mg/day, n = 219), consisted of a 6-week acute phase, followed by a 6-week continuation phase. Symptomatic remission rates were similar for olanzapine- and haloperidol-treated patients at weeks 6 and 12. At week 6, significant changes in five dimensions of the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) [general health (P = 0.010), physical functioning (P < 0.001), role limitations due to physical problems (P < 0.001), social functioning (P < 0.05) and vitality (P < 0.01)] and the SF-36 physical components summary score were found in favour of olanzapine compared to haloperidol. At week 12, olanzapine treatment maintained the significantly favourable HRQOL changes. At the end of week 12, patients on olanzapine showed significantly greater improvement than haloperidol in work activities impairment and household activities impairment scores on the Streamlined Longitudinal Interview Clinical Evaluation from the Longitudinal Interval Follow-up Evaluation (SLICE/LIFE) activities impairment scores. Subgroup analyses revealed that olanzapine treatment significantly increased a proportion of employed patients and their weekly paid working hours. In conclusion, compared to haloperidol, olanzapine treatment was comparably effective in the remission of bipolar mania and significantly improved HRQOL and work status in patients with bipolar I disorder.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Female; Haloperidol; Humans; Male; Olanzapine; Pirenzepine; Quality of Life; Treatment Outcome; Work

Nine hundred and ten schizophrenic inpatients suffering from acute psychotic episodes were included in a naturalistic study. Patients were prescribed treatment with olanzapine (OLZ) or with typical antipsychotic (TYP) drugs. Patients receiving another atypical antipsychotic were excluded. Of the whole sample, 483 (53.4%) were treated with olanzapine and 421 (46.6%) with typical antipsychotics. Three specific subpopulations of greater severity were defined: patients with prominent psychotic symptoms, agitated patients, and patients initially treated with intramuscular (i.m.) medication because of their acute clinical condition. Severity of illness was assessed using the Clinical Global Impression (CGI) scale for severity, the Brief Psychiatric Rating Scale (BPRS) and the Nursing Observational Scale for Inpatient Evaluation. Baseline differences were adjusted per data analysis. The mean change from baseline to endpoint of overall symptomatology (total BPRS score) was significantly greater in the olanzapine group compared to the typical antipsychotic-treated group, both in the sample of patients with prominent positive symptoms (P < 0.001) and in the sample of agitated patients (P =0.015). Significant differences were also found in BPRS positive scores, BPRS negative scores and CGI scores in these two populations. Patients who had received previous i.m. drugs showed no statistically significant differences in symptomatic improvement between both treatments groups, except for a more favourable response of BPRS negative subscores in the olanzapine group (P =0.015). The results suggest that olanzapine may be considered as a first line treatment for severely psychotic inpatients with schizophrenia.

Topics: Acute Disease; Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Schizophrenia; Severity of Illness Index; Treatment Outcome

A 6-week double-blind, randomized, placebo-controlled trial was conducted to determine the efficacy of combined therapy with olanzapine and either valproate or lithium compared with valproate or lithium alone in treating acute manic or mixed bipolar episodes.. The primary objective was to evaluate the efficacy of olanzapine (5-20 mg/d) vs placebo when added to ongoing mood-stabilizer therapy as measured by reductions in Young Mania Rating Scale (YMRS) scores. Patients with bipolar disorder (n = 344), manic or mixed episode, who were inadequately responsive to more than 2 weeks of lithium or valproate therapy, were randomized to receive cotherapy (olanzapine + mood-stabilizer) or monotherapy (placebo + mood-stabilizer).. Olanzapine cotherapy improved patients' YMRS total scores significantly more than monotherapy (-13.11 vs -9.10; P = .003). Clinical response rates (> or = 50% improvement on YMRS) were significantly higher with cotherapy (67.7% vs 44.7%; P< .001). Olanzapine cotherapy improved 21-item Hamilton Depression Rating Scale (HAMD-21) total scores significantly more than monotherapy (4.98 vs 0.89 points; P< .001). In patients with mixed-episodes with moderate to severe depressive symptoms (DSM-IV mixed episode; HAMD-21 score of > or = 20 at baseline), olanzapine cotherapy improved HAMD-21 scores by 10.31 points compared with 1.57 for monotherapy (P< .001). Extrapyramidal symptoms (Simpson-Angus Scale, Barnes Akathisia Scale, Abnormal Involuntary Movement Scale) were not significantly changed from baseline to end point in either treatment group. Treatment-emergent symptoms that were significantly higher for the olanzapine cotherapy group included somnolence, dry mouth, weight gain, increased appetite, tremor, and slurred speech.. Compared with the use of valproate or lithium alone, the addition of olanzapine provided superior efficacy in the treatment of manic and mixed bipolar episodes.

Topics: Acute Disease; Adult; Antimanic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Lithium Carbonate; Male; Middle Aged; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Treatment Outcome; Valproic Acid

To determine whether severity of obsessive-compulsive symptoms (OCS) differs during treatment with olanzapine or risperidone and to establish whether duration of antipsychotic treatment is related to severity of OCS.. We conducted a prospective study of consecutively hospitalized young patients (mean age = 22.4 years) with DSM-IV schizophrenia or related disorders (N = 113) who were treated with olanzapine or risperidone. Olanzapine or risperidone was randomly prescribed for patients who were drug-naive or were treated with typical antipsychotics before admission (N = 36). Patients who had started olanzapine (N = 39) or risperidone treatment (N = 23) prior to admission continued with that medication if they showed initial clinical response. Patients who prior to admission started olanzapine (N = 6) or risperidone (N = 9) but showed no response or suffered from adverse effects switched at admission to risperidone or olanzapine, respectively. Medical records, parents, and patients revealed information on duration of treatment and compliance with olanzapine or risperidone prior to admission. The Yale-Brown Obsessive Compulsive Scale (YBOCS) was administered at admission and 6 weeks thereafter.. At baseline and 6-week assessments, OCS were found in about 30% of 106 evaluable cases and 15% met DSM-IV criteria for obsessive-compulsive disorder. No differences in OCS were found in the patients randomly assigned to olanzapine or risperidone. The 35 subjects treated with olanzapine at both assessments had significantly (p = .01) more severe OCS at week 6 than the 20 subjects treated with risperidone at both assessments. Duration of treatment with olanzapine was significantly (p < .01) related to severity of OCS.. There are no differences in the short-term propensity of olanzapine or risperidone to induce or exacerbate OCS. However, severity of OCS was associated with duration of treatment with olanzapine.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Comorbidity; Female; Humans; Longitudinal Studies; Male; Netherlands; Obsessive-Compulsive Disorder; Olanzapine; Pirenzepine; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders; Risperidone; Schizophrenia; Severity of Illness Index; Treatment Outcome

This double-blind study investigated the efficacy and safety of rapid-acting intramuscular olanzapine in treating agitation associated with Alzheimer's disease and/or vascular dementia. At 2 h, olanzapine (5.0 mg, 2.5 mg) and lorazepam (1.0 mg) showed significant improvement over placebo on the PANSS Excited Component (PANSS-EC) and Agitation-Calmness Evaluation Scale (ACES), and both 5.0 mg olanzapine and lorazepam showed superiority to placebo on the Cohen-Mansfield Agitation Inventory. At 24 h, both olanzapine groups maintained superiority over placebo on the PANSS-EC; lorazepam did not. Olanzapine (5.0 mg) and lorazepam improved ACES scores more than placebo. Simpson-Angus and Mini-Mental State Examination scores did not change significantly from baseline. Sedation (ACES > or =8), adverse events, and laboratory analytes were not significantly different from placebo for any treatment. No significant differences among treatment groups were seen in extrapyramidal symptoms or in corrected QT interval at either 2 h or 24 h, and no significant differences among treatment groups were seen in vital signs, including orthostasis. Intramuscular injection of olanzapine may therefore provide substantial benefit in rapidly treating inpatients with acute dementia-related agitation.

Topics: Acute Disease; Aged; Anti-Anxiety Agents; Antipsychotic Agents; Benzodiazepines; Dementia; Double-Blind Method; Female; Humans; Injections, Intramuscular; Lorazepam; Male; Middle Aged; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Psychomotor Agitation

An intramuscular (IM) formulation of olanzapine has been developed because there are no rapid-acting IM atypical antipsychotic drugs currently available in the United States for treating acute agitation in patients with schizophrenia.. Recently hospitalized acutely agitated patients with schizophrenia (N = 270) were randomized to receive 1 to 3 IM injections of olanzapine (2.5, 5.0, 7.5, or 10.0 mg), haloperidol (7.5 mg), or placebo within 24 hours. A dose-response relationship for IM olanzapine in the reduction of agitation was assessed by measuring the reduction in Positive and Negative Syndrome Scale Excited Component (PANSS-EC) scores 2 hours after the first injection. Safety was assessed by recording adverse events and with extrapyramidal symptom scales and electrocardiograms at 24 hours after the first injection.. Olanzapine exhibited a dose-response relationship for reduction in agitation (F(1,179)= 14.4; P<.001). Mean PANSS-EC reductions 2 hours after the first injection of olanzapine (2.5 mg = -5.5; 5.0 mg = -8.1; 7.5 mg = -8.7; 10.0 mg = -9.4) were superior to those with placebo (-2.9; P =.01 vs olanzapine at 2.5 mg; P<.001 for each other olanzapine dose) but not with haloperidol (-7.5). A dose of 5.0, 7.5, or 10.0 mg of olanzapine caused a greater reduction in agitation than placebo 30 minutes after the first injection. There were no differences between treatment groups for hypotension, the most frequently reported adverse event, or for clinically relevant changes in the QTc interval. There was a greater incidence of treatment-emergent parkinsonism during treatment with IM haloperidol (16.7%) than with 2.5 (P =.03), 5.0 (P =.03), or 7.5 mg (P =.01) of IM olanzapine (0%) or with placebo (0%) (P =.01).. Intramuscular olanzapine at a dose of 2.5 to 10.0 mg per injection exhibits a dose-response relationship in the rapid treatment of acute agitation in patients with schizophrenia and demonstrates a favorable safety profile.

Topics: Acute Disease; Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Haloperidol; Humans; Injections, Intramuscular; Male; Middle Aged; Olanzapine; Pirenzepine; Placebos; Psychiatric Status Rating Scales; Psychomotor Agitation; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

The effects of olanzapine and divalproex for the treatment of mania were compared in a large randomized clinical trial.. A 3-week, randomized, double-blind trial compared flexibly dosed olanzapine (5-20 mg/day) to divalproex (500-2500 mg/day in divided doses) for the treatment of patients hospitalized for acute bipolar manic or mixed episodes. The Young Mania Rating Scale and the Hamilton Depression Rating Scale were used to quantify manic and depressive symptoms, respectively. Safety was assessed with several measures.. The protocol defined baseline-to-endpoint improvement in the mean total score on the Young Mania Rating Scale as the primary outcome variable. The mean Young Mania Rating Scale score decreased by 13.4 for patients treated with olanzapine (N=125) and 10.4 for those treated with divalproex (N=123). A priori categorizations defined response and remission rates: 54.4% of olanzapine-treated patients responded (> or = 50% reduction in Young Mania Rating Scale score), compared to 42.3% of divalproex-treated patients; 47.2% of olanzapine-treated patients had remission of mania symptoms (endpoint Young Mania Rating Scale < or = 12), compared to 34.1% of divalproex-treated patients. The decrease in Hamilton depression scale score was similar in the two treatment groups. Completion rates for the 3-week study were similar in both groups. The most common treatment-emergent adverse events (incidence >10%) occurring more frequently during treatment with olanzapine were dry mouth, increased appetite, and somnolence. For divalproex, nausea was more frequently observed. The average weight gain with olanzapine treatment was 2.5 kg, compared to 0.9 kg with divalproex treatment.. The olanzapine treatment group had significantly greater mean improvement of mania ratings and a significantly greater proportion of patients achieving protocol-defined remission, compared with the divalproex treatment group. Significantly more weight gain and cases of dry mouth, increased appetite, and somnolence were reported with olanzapine, while more cases of nausea were reported with divalproex.

Topics: Acute Disease; Adult; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Female; Humans; Male; Olanzapine; Pirenzepine; Treatment Outcome; Valproic Acid

Behavioral agitation and prominent positive psychotic symptoms often characterize the acute presentation of schizophrenia. The clinical treatment goal is a rapid control of these symptoms. The relative efficacy of olanzapine, a novel antipsychotic drug, was compared with that of the conventional antipsychotic drug haloperidol. A post hoc analysis conducted on a large multicenter, double-blind, 6-week study of acute-phase patients with DSM-III-R schizophrenia or schizophreniform or schizoaffective disorders treated with olanzapine (5-20 mg/day) or haloperidol (5-20 mg/day) assessed the treatment effects on agitation (Brief Psychiatric Rating Scale [BPRS] agitation score) and positive symptoms (BPRS positive symptom score). Overall, olanzapine-treated patients experienced significantly greater improvement in behavioral agitation than did haloperidol-treated patients (last observation carried forward [LOCF]; p < .0002). Both groups showed similar reductions in agitation scores during the first 3 weeks of therapy; olanzapine was associated with significantly greater improvements at weeks 4, 5, and 6 (observed cases [OC]). Similarly, patients with predominantly positive psychotic symptoms experienced significantly greater improvement in BPRS positive symptom scores with olanzapine compared with haloperidol (LOCF; p = .013). In olanzapine-treated patients, improvement in BPRS agitation and positive symptom scores was significantly greater at weeks 4, 5, and 6 (agitation scores, p < or = .01; positive symptom scores, p < .05) (OC). These data suggest that olanzapine may be considered a first-line treatment for the patient in an acute episode of schizophrenia.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Brief Psychiatric Rating Scale; Double-Blind Method; Female; Haloperidol; Humans; Male; Olanzapine; Pirenzepine; Prospective Studies; Psychiatric Status Rating Scales; Psychomotor Agitation; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Rapid tranquilization of acutely psychotic patients with schizophrenia is usually carried out using typical antipsychotic agents. The objective of such treatment is to control agitation, not to treat psychosis, which usually responds only after a few weeks of treatment. An intramuscular formulation of the atypical antipsychotic olanzapine was developed for treatment of agitation in acutely psychotic patients. Studies conducted to assess control of agitation in schizophrenia also investigated the positive symptom efficacy of olanzapine when used to provide rapid tranquilization. This article summarizes the results of 3 clinical trials with intramuscular olanzapine with regard to positive symptom efficacy as measured by the Brief Psychiatric Rating Scale (BPRS; 0-6 scale) positive subscale. In 2 open-label trials, patients treated with intramuscular olanzapine experienced a mean decrease from baseline in BPRS positive subscale score. In 1 double-blind clinical trial of intramuscular olanzapine versus intramuscular haloperidol and intramuscular placebo, the mean decrease from baseline in BPRS positive subscale score for patients treated with intramuscular olanzapine was statistically significant (p < .05). In all 3 studies, positive symptom improvement continued following transition to oral olanzapine. These results suggest that intramuscular olanzapine has positive symptom efficacy early in the course of treatment and may provide a smooth transition to maintenance therapy with oral olanzapine.

Topics: Acute Disease; Administration, Oral; Adult; Antipsychotic Agents; Benzodiazepines; Brief Psychiatric Rating Scale; Double-Blind Method; Drug Administration Schedule; Female; Haloperidol; Hospitalization; Humans; Injections, Intramuscular; Male; Olanzapine; Pirenzepine; Psychomotor Agitation; Schizophrenia; Schizophrenic Psychology; Single-Blind Method; Treatment Outcome

There may be a temporal association between some antipsychotics and prolongation of the heart-rate-corrected QT interval (QTc) representing a delay in ventricular repolarization. QTc prolongation significantly exceeding normal intra-individual and interindividual variation may increase the risk of ventricular tachydysrhythmias, especially torsade de pointes, and therefore, sudden cardiac death.. Electrocardiogram recordings obtained as part of the safety assessment of olanzapine in 4 controlled, randomized clinical trials (N = 2,700) were analyzed. These analyses were conducted to characterize any change in QTc temporally associated with olanzapine, compared with placebo, haloperidol, and risperidone, in acutely psychotic patients (DSM-III-R and DSM-IV) and to characterize variability and temporal course of the QTc in this patient population. Changes from baseline to minimum and maximum QTc were tested for significance, and baseline to acute-phase endpoint change in mean QTc was tested for significance within treatments and for differences between olanzapine and comparators. The possibility of a linear relationship between dose of olanzapine and mean change in QTc, as well as incidence of treatment-emergent prolongation of QTc (change from < 430 msec at baseline to > or =430 msec at endpoint), was tested.. The incidence of maximum QTc > or = 450 msec during treatment was approximately equal to the incidence of QTc > or =450 msec at baseline.. Results of these analyses suggest that olanzapine, as therapeutically administered to patients with schizophrenia and related psychoses, does not contribute to QTc prolongation resulting in potentially fatal ventricular arrhythmias.

Topics: Acute Disease; Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Aged; Antipsychotic Agents; Arrhythmias, Cardiac; Benzodiazepines; Electrocardiography; Female; Haloperidol; Humans; Incidence; Long QT Syndrome; Male; Middle Aged; Olanzapine; Pirenzepine; Placebos; Risperidone; Schizophrenia

The authors evaluated the comparative efficacy and safety of intramuscular olanzapine, intramuscular haloperidol, and intramuscular placebo for the treatment of acute agitation in schizophrenia.. Hospitalized patients with schizophrenia received one to three injections of intramuscular olanzapine, 10 mg, intramuscular haloperidol, 7.5 mg, or intramuscular placebo over a 24-hour period. Agitation was measured with the excited component of the Positive and Negative Syndrome Scale and two additional scales.. According to scores on the excited component of the Positive and Negative Syndrome Scale, both intramuscular olanzapine and intramuscular haloperidol reduced agitation significantly more than intramuscular placebo 2 and 24 hours following the first injection. Intramuscular olanzapine reduced agitation significantly more than intramuscular haloperidol 15, 30, and 45 minutes following the first injection. No patients treated with intramuscular olanzapine experienced acute dystonia, compared with 7% of those who were treated with intramuscular haloperidol. No significant QT(c) interval changes were observed in any patients.. Intramuscular olanzapine represents a rapid, effective, and safe treatment for acute agitation in schizophrenia.

Topics: Acute Disease; Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Haloperidol; Humans; Injections, Intramuscular; Male; Olanzapine; Pirenzepine; Placebos; Psychiatric Status Rating Scales; Psychomotor Agitation; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Thirty adult patients with acute schizophrenia were included into six-week open-labelled, non-comparative trial of olanzapine with free dosing from 5 to 20 mg per day. For assessment of efficacy and safety of the treatment PANSS, BPRS, CGL and ESRS scales were used. The main criterion of improvement was the percentage of reduction of BPRS score to the end of the trial. More than 50% reduction was achieved in 23% of the patients, more than 20%--in 57% of the cases; 20% were non-responders (reduction less than 20%). Changes in the scores of the positive and negative PANSS subscales were significant (p < 0.001) starting from the second week of treatment. There was no correlation in changes in positive and negative scores as well as in changes in negative and ESRS scores. The first signs of the antipsychotic effect (a reduction of tension, suspiciousness and fear) appeared just in the first two weeks of treatment and manifested in the reduction of delusions and hallucinations. Reduction of depression didn't correlate with changes in scores of the positive or negative PANSS subscales. The changes in behavioral and cognitive symptoms were statistically significant starting from the second week of treatment. No clinically significant signs of extrapiramidal syndrome or other side-effects except weight gain were observed during the trial.

Topics: Acute Disease; Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Brief Psychiatric Rating Scale; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Schizophrenia; Treatment Outcome

We compared the efficacy and safety of olanzapine vs placebo for the treatment of acute bipolar mania.. Four-week, randomized, double-blind, parallel study. A total of 115 patients with a DSM-IV diagnosis of bipolar disorder, manic or mixed, were randomized to olanzapine, 5 to 20 mg/d (n = 55), or placebo (n = 60). The primary efficacy measure was the Young-Mania Rating Scale (Y-MRS) total score. Response and euthymia were defined, a priori, as at least a 50% improvement from baseline to end point and as a score of no less than 12 at end point in the Y-MRS total score, respectively. Safety was assessed using adverse events, Extrapyramidal Symptom (EPS) rating scales, laboratory values, electrocardiograms, vital signs, and weight change.. Olanzapine-treated patients demonstrated a statistically significant greater mean (+/- SD) improvement in Y-MRS total score than placebo-treated patients (-14.8 +/- 12.5 and -8.1 +/- 12.7, respectively; P<.001), which was evident at the first postbaseline observation 1 week after randomization and was maintained throughout the study (last observation carried forward). Olanzapine-treated patients demonstrated a higher rate of response (65% vs 43%, respectively; P =.02) and euthymia (61% vs 36%, respectively; P =. 01) than placebo-treated patients. There were no statistically significant differences in EPSs between groups. However, olanzapine-treated patients had a statistically significant greater mean (+/- SD) weight gain than placebo-treated patients (2.1 +/- 2.8 vs 0.45 +/- 2.3 kg, respectively) and also experienced more treatment-emergent somnolence (21 patients [38.2%] vs 5 [8.3% ], respectively).. Olanzapine demonstrated greater efficacy than placebo in the treatment of acute bipolar mania and was generally well tolerated.

Topics: Acute Disease; Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Placebos; Psychiatric Status Rating Scales; Severity of Illness Index; Sleep Wake Disorders; Treatment Outcome; Weight Gain

The first episode of an illness may respond differently to any treatment compared to multiple episodes of the same illness. This study details the treatment response of six first-episode manic patients who participated in a previously reported study of 139 subjects comparing olanzapine to placebo in bipolar I mania (Tohen M, Sanger TM, McElroy SL, Tollefson GD, Chengappa KNR, Daniel DG. Olanzapine versus placebo in the treatment of acute mania. Am J Psychiatry 1999; 156: 702-709).. Six first-episode subjects participated in a 3-week double-blind, random assignment, parallel group, placebo-controlled study of olanzapine for bipolar mania. The Young Mania Rating Scale (Y-MRS), Clinical Global Impression, and Hamilton Depression ratings were administered weekly. Lorazepam as rescue medication was permitted for the first 10 days.. Five subjects were randomized to placebo and one to olanzapine. Two subjects (40%) with psychotic mania (who also had their first-illness episode) were assigned to placebo and responded with greater than 50% reduction in the Y-MRS score and also remitted in 3 weeks. Another placebo-assigned subject had a 46% reduction in the Y-MRS scores, and two placebo-assigned subjects worsened. The olanzapine-assigned subject had a 44% reduction in the Y-MRS score. In contrast, 34 of 69 (48.6%) multiple-episode olanzapine subjects responded and 14 of 61 (23.0%) of placebo-treated subjects did.. This preliminary data set suggest there may be differences in treatment response between first-illness episode versus multi-episode bipolar manic subjects. Larger numbers of subjects with these illness characteristics are needed to either confirm or refute this suggestion.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Placebo Effect

The effectiveness of antipsychotic monotherapy in schizoaffective disorder is limited, and further constrained by safety concerns.. We aimed to compare the efficacy, tolerability and safety profile of the new pharmaceutical, olanzapine, with haloperidol.. Data were assessed from 300 DSM-III-R schizoaffective subjects from a larger double-blind prospective international study. Subjects were randomly allocated to six weeks of olanzapine (5-20 mg) or haloperidol (5-20 mg) treatment; responders were followed for up to one year of double-blind, long-term maintenance therapy.. Olanzapine-treated patients achieved a statistically significant greater improvement than haloperidol treated patients on overall measures of efficacy, including clinical response. Significantly fewer olanzapine patients left the study early, and fewer adverse events were observed among those receiving olanzapine. During maintenance, olanzapine-treated patients continued to experience additional improvement, with fewer EPS but more weight gain than those on haloperidol.. Olanzapine demonstrated substantial advantages over the conventional antipsychotic haloperidol in the management of schizoaffective disorder.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Female; Haloperidol; Humans; Male; Olanzapine; Pirenzepine; Prospective Studies; Psychotic Disorders; Treatment Outcome

The primary intent of this study was to compare the efficacy and safety of olanzapine and placebo in the treatment of acute mania.. The design involved a random-assignment, double-blind, placebo-controlled parallel group study of 3 weeks' duration. After a 2- to 4-day screening period, qualified patients were assigned to either olanzapine (N = 70) or placebo (N = 69). Patients began double-blind therapy with either olanzapine, 10 mg, or placebo given once per day. After the first day of treatment, the daily dose could be adjusted upward or downward, as clinically indicated, by one capsule (olanzapine, 5 mg/day) within the allowed range of one to four capsules. The primary efficacy measure in the protocol was defined as a change from baseline to endpoint in total score on the Young Mania Rating Scale. Clinical response was defined a priori as a decrease of 50% or more from baseline in Young Mania Rating Scale total score.. The olanzapine group experienced significantly greater mean improvement in Young Mania Rating Scale total score than the placebo group. On the basis of the clinical response criteria, significantly more olanzapine-treated patients (48.6%) responded than those assigned to placebo (24.2%). Somnolence, dizziness, dry mouth, and weight gain occurred significantly more often with olanzapine. There were no statistically significant differences between the olanzapine-treated and placebo-treated patients with respect to measures of parkinsonism, akathisia, and dyskinesias. No discontinuations of treatment due to adverse events occurred in the olanzapine treatment group.. The results from this study suggest that compared with placebo, olanzapine has superior efficacy for the symptoms of acute mania.

Topics: Acute Disease; Adolescent; Adult; Aged; Akathisia, Drug-Induced; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Drug Administration Schedule; Female; Headache; Humans; Male; Middle Aged; Olanzapine; Patient Dropouts; Pirenzepine; Placebos; Psychiatric Status Rating Scales; Sleep; Treatment Outcome

Two studies compared the efficacy of standard-dose oral olanzapine (5 to 15 mg a day) with placebo and with ineffective-dose olanzapine (1 mg a day) in maintenance therapy of schizophrenia.. The studies were 46-week double-blind extensions of multicenter studies that assessed the efficacy of olanzapine in the acute treatment of schizophrenia. Subjects were 120 adults who met DSM-III-R criteria for schizophrenia with an acute exacerbation and who had a minimum score of 24 on the Brief Psychiatric Rating Scale, who had responded to acute therapy (defined as at least a 40 percent reduction in the BPRS score from baseline or a score of 18 or less during up to six weeks of treatment), and who were outpatients at their last acute-phase visit. Relapse was defined as hospitalization for psychopathology. Relapse risk was analyzed using Kaplan-Meier survival analysis and life table analysis. Patients who relapsed were discontinued from the studies.. In the first study (N = 58), patients in the standard-dose olanzapine group experienced a significantly lower relapse risk (p = .002) over one year than patients treated with placebo. The estimated one-year risk of relapse with olanzapine was 28.6 percent, compared with 69.9 percent with placebo. Results were similar in the second study (N = 62); patients treated with standard-dose olanzapine had a significantly reduced risk of relapse (p = .018) over one year compared with patients treated with ineffective-dose olanzapine. The estimated one-year risks of relapse were 19.6 percent for standard-dose olanzapine and 45.5 percent for ineffective-dose olanzapine.. Olanzapine is superior to placebo and ineffective-dose olanzapine in the maintenance therapy of schizophrenia.

Topics: Acute Disease; Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Drug Administration Schedule; Female; Humans; Life Tables; Male; Middle Aged; Olanzapine; Pirenzepine; Placebos; Psychiatric Status Rating Scales; Recurrence; Risk Factors; Schizophrenia; Schizophrenic Psychology; Survival Analysis; Treatment Outcome

Topics: Acute Disease; Eye Diseases; Glaucoma, Angle-Closure; Humans; Olanzapine

Olanzapine is a second-generation antipsychotic (SGA) used frequently in the treatment of schizophrenia and a growing list of off-label conditions. Though effective in reducing psychoses, acute olanzapine treatment causes rapid increases in blood glucose that are believed to be mediated by increases in liver glucose output, skeletal muscle insulin resistance, and beta cell dysfunction. Further, the acute lipidemic response to olanzapine has been largely unexplored. While females have been reported to be more susceptible to olanzapine-induced weight gain, there is little known about the impact of sex on the acute response to SGAs. The purpose of this study was to determine if the acute effects of SGAs on glucose and lipid metabolism display a sexually dimorphic response in C57BL/6 J mice and examine potential mechanisms mediating this effect. Age matched male and female C57BL/6 J mice were treated with olanzapine (5 mg/ kg, IP) or vehicle control and blood glucose was measured at baseline, 15, 30, 60, 90, and 120 min post-treatment and tissues and serum harvested. These experiments were repeated, and mice underwent an insulin (0.5 IU/kg) or pyruvate tolerance test (2 g/kg) following 60 min of olanzapine treatment. Females were protected against olanzapine-induced increases in blood glucose and pyruvate intolerance compared to male mice, and this occurred despite the development of severe insulin resistance. In male mice olanzapine increased the glucagon:insulin ratio whereas in females this ratio was reduced. When challenged with exogenous glucagon (1 mg/kg IP), females were less responsive than males. Male and female mice displayed similar increases in whole body fatty acid oxidation, serum fatty acids and liver triglyceride accumulation. Our findings provide evidence that while there are no apparent sex differences in the lipid metabolism response to olanzapine, that females are protected from acute olanzapine-induced excursions in blood glucose. This is likely due in part to reductions in the glucagon:insulin ratio and glucagon responsiveness which could impact olanzapine induced increases in liver glucose production.

Topics: Acute Disease; Animals; Blood Glucose; Female; Glucose Tolerance Test; Hyperglycemia; Insulin; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; Olanzapine; Severity of Illness Index; Sex Characteristics

Antipsychotics have been the mainstay of the treatment of schizophrenia, and their potential role in neuroprotection could be related to brain-derived neurotrophic factor (BDNF). So far different effects on both serum and plasma levels of BDNF were reported related to the various antipsychotic treatments. Aim of this study was to investigate the influence of olanzapine or risperidone on both plasma and serum levels of BDNF in patients with acute schizophrenia. For 50 participants with acute episode of schizophrenia both plasma and serum BDNF, along with the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression scale, were assessed pretreatment and post treatment - after 6 weeks of either risperidone or olanzapine. Results show that a weak correlation between pretreatment plasma and serum levels of BNDF was found no longer significant after 6 weeks of treatment. Antipsychotics, olanzapine and risperidone showed no significant effect on post treatment plasma and serum levels of BDNF. Pretreatment plasma level of BDNF and PANSS positive subscale were positively correlated. Post treatment serum level of BDNF and Clinical Global Impression were negatively correlated. In conclusion, plasma and serum BDNF levels could be different markers to some extent with regard to clinical symptoms, response to therapy and outcome. The interrelation between serum and plasma BDNF should be established in further studies.

Topics: Acute Disease; Adult; Age Factors; Antipsychotic Agents; Benzodiazepines; Brain-Derived Neurotrophic Factor; Female; Humans; Male; Middle Aged; Olanzapine; Prospective Studies; Risperidone; Schizophrenia; Sex Factors; Young Adult

Treatment with low-potency anti-psychotic agents is an important risk factor in the development of pulmonary embolism (PE). We report a case of 74years old female patient receiving olanzapine for psychotic depression admitted to the emergency service with the complaints of chest pain and shortness of breath. She had tachypnea, hypotension and tachycardia. Arterial blood gas analysis showed hypoxemia-hypocapnia and D-dimer level was high. Computed tomographic pulmonary angiography (CTPA) demonstrated pulmonary embolism in both main pulmonary arteries, through lobar and segmental branches. Tissue plasminogen activator (t-PA) was administered in intensive care unit. As the only possible risk factor for PE was olanzapine, olanzapine treatment was terminated with pyschiatry consultation. During the 12-month follow-up of the patient; malignancy was not observed. Diagnosis and prevention of PE are the important goals to reduce morbidity and mortality in subjects receiving olanzapine.

Topics: Acute Disease; Aged; Anticoagulants; Benzodiazepines; Computed Tomography Angiography; Depression; Female; Humans; Olanzapine; Pulmonary Embolism; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index; Warfarin

Olanzapine is an atypical antipsychotic indicated for the treatment of schizophrenia and known to be effective in the management of delirium. In addition to its use for these indications olanzapine has also been used in the management of chemotherapy induced nausea and vomiting and otherwise difficult to control nausea and vomiting in palliative care settings. Although considered to be well tolerated with a lower incidence of extrapyramidal effects than first generation antipsychotics there are a small number of reports of olanzapine inducing delirium. Reported here are two cases of "probable" acute cognitive impairment following treatment of nausea with olanzapine. The cognitive impairment associated with olanzapine is probably mediated through its activity at cholinergic receptors a known risk factor for delirium particularly in the elderly.

Topics: Acute Disease; Aged; Antiemetics; Benzodiazepines; Delirium; Humans; Male; Nausea; Olanzapine

We report the patient of a 53-year-old woman who developed subacute-onset marked tonge protrusion and bite. She was diagnosed as dementia with Lewy bodies (DLB) from the clinical features including progressive cognitive decline, visual hallucinations, parkinsonism, and severe insomnia and depression, and the radiological finding of low dopamine transported uptake in basal ganglia by Dat SCAN and low blood circulation in occipital lobe of cerebrum. The patient received 600 mg doses of levodopa for over a year, followed by rotigotine and ropinirole with a rapid increase of dosage. It is believed that these treatments stimulated and sensitized dopamine D1 receptors, thereby inducing lingual dystonia. Furthermore, the patient demonstrated dyspnea and attacks of apnea caused by the closure of bilateral vocal cords due to laryngeal dyskinesia. After initiation of the neuroleptic, olanzapine, for a short duration, the high dose of levodopa overlapped with neuroleptic sensitivity, suggesting DOPA-induced dystonia and dyskinesia. This interaction can sometimes lead to lethal adverse events, and must be considered very important when treating patients with DLB.

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Bites and Stings; Drug Interactions; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Dystonia; Female; Humans; Indoles; Laryngeal Diseases; Levodopa; Lewy Body Disease; Middle Aged; Olanzapine; Receptors, Dopamine D1; Tetrahydronaphthalenes; Thiophenes; Tongue Diseases

Topics: Acute Disease; Adolescent; Adrenal Cortex Hormones; Adult; Anti-Anxiety Agents; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Antipsychotic Agents; Benzodiazepines; Cognitive Dysfunction; Diagnosis, Differential; Humans; Immunoglobulins; Lorazepam; Male; Mental Disorders; Olanzapine; Treatment Outcome; Young Adult

Topics: Acute Disease; Aged; Antipsychotic Agents; Benzodiazepines; Female; Glaucoma, Angle-Closure; Humans; Olanzapine; Vision, Low

The efficacy and safety of olanzapine monotherapy in bipolar depression has been evaluated in 2 placebo-controlled studies.. We pooled data from 2 previously published studies examining olanzapine monotherapy in patients with bipolar I depression. Changes from baseline to 6 weeks in Montgomery-Åsberg Depression Rating Scale (MADRS) total score, MADRS-6 (included items: apparent sadness, reported sadness, inner tension, lassitude, inability to feel, and pessimistic thoughts) score, and individual MADRS item scores were assessed with an analysis of variance (ANOVA) model. Influence of patient baseline characteristics (age, gender, MADRS total score, age at onset of bipolar disorder, psychotic features, melancholic feature, mixed features [≥2 on ≥3 Young Mania Rating Scale items], and racial origin) on the efficacy of olanzapine monotherapy was examined with an ANOVA model for each factor and stepwise multiple regression analysis.. Included were a total of 690 olanzapine-group and 524 placebo-group patients. MADRS total, MADRS-6, and all individual MADRS item scores (except concentration difficulties and suicidal thoughts) showed significantly (P≤0.05) greater decreases from baseline to 6 weeks in olanzapine-treated patients than those on placebo. The only baseline characteristic associated with response to olanzapine was melancholic feature.. The study was limited by omission of patients with bipolar II disorder, post hoc analysis of data from only two clinical trials, and exclusion of suicidal patients.. Olanzapine monotherapy improved core symptoms of depression in patients with bipolar I depression. Additionally, we identified melancholic feature as a baseline factor associated with improved treatment response to olanzapine.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Female; Humans; Male; Middle Aged; Olanzapine; Randomized Controlled Trials as Topic

Acute catatonia is a non-specific, relatively frequent syndrome, which manifests itself through characteristic motor signs that enables its diagnosis. It occurs in association with mood disorders, psychotic disorders and several somatic or toxic diseases. Its short-term prognosis is of paramount importance. Without effective treatment, it is associated with high mortality. Despite the vital risk inherent in this disorder, it is not recognized as an independent diagnostic category by international rankings, which makes its diagnostic detection difficult and consequently does not allow adequate therapeutic care. However, if benzodiazepines and electroconvulsive therapy have proved effective in the treatment of acute catatonia, the role of atypical antipsychotics remains controversial. In fact, despite the progress made by the DSM-IV-TR and CIM 10 by the recognition of the etiologic diversity of catatonia, we deplore the absence to date of a consensus on clinical management and therapy of catatonia, which constitutes a source of confusion for practitioners in their approach to catatonic patients. To illustrate the difficulty in supporting these patients, we report here a clinical vignette.. Mr. M. aged 21, without psychiatric history, has shown a functional acute psychotic episode involving a delirious and hallucinatory syndrome associated with a marked catatonic dimension. Olanzapine was initiated at a dose of 10mg/d on the nineth day of hospitalization; the clinical picture was complicated by a malignant catatonia justifying the halt of olanzapine and the institution, in intensive units, of 15mg per day of lorazepam. After 72hours, the patient has not responded to this treatment. ECT was expected, but the patient died on the 12th day.. This case raises a threefold question: the crucial issue of immediate vital prognosis, that of the truthfulness of the positive diagnosis of this psychotic table and finally the issue of therapeutic care, primarily the well-founded or otherwise use of an atypical antipsychotic for the treatment of this type of psychotic disorder. For Mr. M., the clinical diagnosis that he has shown, according to the DSM IV-TR, is brief psychotic disorder "temporary diagnosis". This diagnosis - brief psychotic disorder - does not actually allow for a specific clinical approach to this type of psychotic table. The immediate vital prognosis inherent in the catatonic dimension may not be properly evaluated and the therapeutic conduct may miss the application of the specific treatment of the catatonic syndrome. The proper diagnosis for this type of psychotic disorder would be "catatonia" as proposed by Taylor and Fink, instead of "brief psychotic disorder" if the international rankings have included this disorder as a separate and independent diagnosis. The identification by international rankings of the catatonic syndrome as an independent diagnostic category seems essential for clinicians to allow: its clinical detection, the establishment of a syndromic diagnosis of catatonic disorder, appropriate prognostic evaluation and finally, the application of a suitable therapeutic strategy. Conventional treatment, benzodiazepine- and/or ECT-based, can solve the catatonic episode in a few days, irrespective of its etiology and its severity. Moreover, while all authors agree that conventional antipsychotics may induce a catatonic state or worsen a preexisting catatonia into a malignant catatonia and should thus be avoided for catatonic patients or with prior catatonic episodes, recent data from the literature emphasize the frequent and successful use of atypical antipsychotics, including olanzapine, in various clinical forms of benign catatonia. However, our patient did not respond to treatment with olanzapine and got even more complicated. Was the malignant catatonia that this patient has shown induced by olanzapine ? The answer to this question seems difficult since some authors report the efficacy of olanzapine in malignant catatonia. We wonder if we should have kept olanzapine and strengthen its dosage like Cassidy et al. in 2001 and Suzuki et al. in 2010 for the treatment of the malignant form constituted in this patient rather than having stopped it and used lorazepam as indica. The non-recognition of catatonia as an independent entity, the lack of a therapeutic consensus and the pending issue on the safety and efficacy of atypical antipsychotics in the treatment of catatonia are at the origin of the difficulties of therapeutic support of catatonic patients.

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Catatonia; Fatal Outcome; Hospitalization; Humans; Male; Olanzapine; Prognosis; Psychotic Disorders; Treatment Failure; Young Adult

Olanzapine (Eli Lilly and Company, Indianapolis, IN) is starting to be used with more frequency in emergency departments (EDs) for agitated patients. The potential complications of the use of olanzapine in combination with a benzodiazepine have not been well characterized in ED patients with undifferentiated agitation.. The measurement of vital signs, repeat medication dosage, and ethanol levels in patients who received parenteral (intramuscular [IM]) olanzapine either alone or concurrently with benzodiazepines.. This is a structured retrospective chart review of all patients who met the criteria of having received IM olanzapine for agitation and having vital signs documented both before medication administration and within 4 h afterwards.. Twenty-five patients were identified as meeting the inclusion criteria. Ten patients received olanzapine and benzodiazepine, and 15 patients received olanzapine alone. Regardless of whether or not they received benzodiazepines, patients who had ingested significant amounts of alcohol before arrival in the ED had decreased oxygen saturations after olanzapine administration. Oxygen saturations decreased more in patients who had ingested alcohol and then received olanzapine + benzodiazepines. Two patients (20%) who received olanzapine + benzodiazepines and who had ingested significant amounts of alcohol exhibited hypoxia, defined as lowest O(2) saturation ≤ 92%.. In this relatively small sample, olanzapine plus benzodiazepines seems to be safe in patients who have not ingested alcohol, but may produce potentially significant oxygen desaturations in patients who have. Future, prospective studies should explore the benefits vs. potential risks of adding a benzodiazepine to olanzapine for agitated patients in the ED.

Topics: Acute Disease; Adult; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Drug Interactions; Drug Therapy, Combination; Emergency Medicine; Emergency Service, Hospital; Ethanol; Female; Humans; Hypoxia; Injections, Intramuscular; Male; Middle Aged; Olanzapine; Oxygen; Psychomotor Agitation; Retrospective Studies; Young Adult

Pharmacologic management of the agitated emergency department patient is controversial. The combination of olanzapine + benzodiazepines is not recommended by the manufacturer, but a recent report suggested harm only if the patient was intoxicated. Whether this is also true for haloperidol + benzodiazepines is not known.. The measurement of vital signs and ethanol levels in patients who received haloperidol with or without benzodiazepines was compared to a previous analysis of patients who received olanzapine with or without benzodiazepines.. This is a structured retrospective chart review of patients who received parenteral haloperidol or parental olanzapine either with or without benzodiazepines.. There were 96 patients (71 haloperidol, 25 olanzapine) who met inclusion criteria. No patient in the olanzapine + benzodiazepine group had hypotension, although one patient in the olanzapine-only group did (6.7%); 2 patients in the haloperidol + benzodiazepines group (5.1%) and 2 patients in the haloperidol-only group (6.3%) had hypotension. In alcohol-negative (ETOH-) patients, neither olanzapine alone nor olanzapine + benzodiazepines was associated with decreased oxygen saturations. In ETOH+ patients, olanzapine alone was not associated with decreased oxygen saturations, but olanzapine + benzodiazepines were associated with lower oxygen saturations than haloperidol + benzodiazepines.. In this sample, olanzapine alone or with a benzodiazepine was not associated with more hypotension than haloperidol. However, olanzapine + benzodiazepines were associated with lower oxygen saturations than haloperidol + benzodiazepines in ETOH+ but not ETOH- patients. In patients with known alcohol ingestion, haloperidol, haloperidol + benzodiazepines, or olanzapine alone may be better choices for treatment of agitation.

Topics: Acute Disease; Adult; Alcoholic Intoxication; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Blood Pressure; Drug Interactions; Drug Therapy, Combination; Emergency Service, Hospital; Female; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Oxygen; Psychomotor Agitation; Retrospective Studies

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Drug Overdose; Female; Humans; Olanzapine; Tablets, Enteric-Coated; Valproic Acid

Published research on agitation is limited by the difficulty in generalizing findings from trials using moderately agitated, carefully selected patients treated with single agents. More specifically, there are few comparative studies examining common intramuscular (IM) regimens (ie, haloperidol with or without benzodiazepines) with IM atypical antipsychotics. Therefore, we conducted a retrospective chart review to compare IM olanzapine and haloperidol in a "real-world" population with agitation.. We performed a retrospective evaluation of charts from 146 consecutive emergency department patients who received either IM haloperidol or IM olanzapine for agitation. We used a clinically oriented proxy marker of efficacy--the necessity for additional medication intervention for agitation (AMI)--as our primary outcome measure.. Additional medication intervention for agitation was required by 43% (13/30) patients when haloperidol was given alone and by 18% (13/72) when haloperidol was given with a benzodiazepine. In the case of olanzapine, AMI was required by 29% (6/21) of patients receiving olanzapine alone and by 18% (2/11) of patients given olanzapine plus a benzodiazepine. A significant percentage of patients had clinical characteristics (nonpsychiatric triage complaint, drug/alcohol use, severe agitation) that differ from more selective samples.. Overall, these finding suggest that in a naturalistic emergency department setting, haloperidol monotherapy is less effective--at least in requiring AMI--than olanzapine with or without a benzodiazepine or haloperidol plus a benzodiazepine. Moreover, these later 3 regimens seemed comparable. Prospective studies examining the treatment of real-world agitation, including head-to-head comparisons of the haloperidol-benzodiazepine combination with newer IM antipsychotics, are needed.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Dose-Response Relationship, Drug; Drug Therapy, Combination; Emergency Service, Hospital; Female; Haloperidol; Humans; Injections, Intramuscular; Male; Medical Records; Middle Aged; Olanzapine; Psychomotor Agitation; Retrospective Studies; Substance-Related Disorders

Bipolar disorder has a significant impact upon a patient's quality of life, imposing a considerable economic burden on the individual, family members and society as a whole. Several medications are indicated for the acute treatment of mania and depression associated with bipolar disorder as well as for maintenance therapy; however, these have varying efficacy, tolerability and costs.. The objective of this study was to develop a new discrete-event simulation model to analyse the long-term consequences of pharmacological therapy for the management of bipolar I and II disorders (acute treatment of episodes of mania and depression as well as maintenance therapy).. Probabilities of remission and relapse were obtained from clinical trial data and meta-analyses. Costs (year 2011 values) were assessed from a UK healthcare payer's perspective, and included pharmacological therapy and resource use associated with the treatment of mood events and selected adverse events. The health effects were measured in terms of QALYs.. For a patient starting with acute depression or in remission at 40 years of age (which was the average age in the clinical trials), quetiapine 300 mg/day was a cost-effective strategy compared with olanzapine 15 mg/day over a 5-year time frame. With acute bipolar depression as a starting episode, the 5-year medical costs were £323 higher and QALYs were 0.038 higher for quetiapine compared with olanzapine, corresponding to a cost-effectiveness ratio of £8600 per QALY gained.. Compared with olanzapine, the results suggest that quetiapine is cost effective as a maintenance treatment for bipolar depression.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Computer Simulation; Cost-Benefit Analysis; Dibenzothiazepines; Humans; Meta-Analysis as Topic; Models, Economic; Olanzapine; Quality-Adjusted Life Years; Quetiapine Fumarate; Remission Induction; Secondary Prevention; United Kingdom

Atypical antipsychotic drugs, such as olanzapine, have been shown to alleviate the positive, negative and, to a lesser degree, the cognitive symptoms of schizophrenia in many patients. However, the detailed mechanisms of action of these drugs have yet to be elucidated. We have carried out the first investigation aimed at evaluating the effects of olanzapine treatment on the glycosylation of serum proteins in schizophrenia patients. Olanzapine treatment resulted in increased levels of a disialylated biantennary glycan and reduced levels of a number of disialylated bi- and triantennary glycans on whole serum glycoproteins. These changes were not observed on a low-abundance serum protein fraction. α1 acid glycoprotein was identified as a carrier of some of the detected altered oligosaccharides. In addition, glycan analysis of haptoglobin, transferrin, and α1 antitrypsin reported similar findings, although these changes did not reach significance. Exoglycosidase digestion analysis showed that olanzapine treatment increased galactosylation and sialylation of whole serum proteins, suggesting increased activity of specific galactosyltransferases and increased availability of galactose residues for sialylation. Taken together, these findings indicate that olanzapine treatment results in altered glycosylation of serum proteins.

Topics: Acute Disease; Adult; alpha 1-Antitrypsin; Antipsychotic Agents; Benzodiazepines; Chromatography, Liquid; Female; Glycomics; Glycoproteins; Glycosylation; Humans; Hydrophobic and Hydrophilic Interactions; Male; Middle Aged; Olanzapine; Orosomucoid; Polysaccharides; Protein Processing, Post-Translational; Schizophrenia, Paranoid; Young Adult

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Emergencies; Emergency Medicine; Emergency Service, Hospital; Evidence-Based Medicine; Haloperidol; Humans; Injections, Intramuscular; Olanzapine; Psychomotor Agitation; Schizophrenia; Treatment Outcome; United Kingdom; Young Adult

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Chemical and Drug Induced Liver Injury; Clozapine; Hepatitis C, Chronic; Humans; Male; Olanzapine; Schizophrenia, Paranoid; Time Factors

A case of acute pancreatitis associated with lisinopril and olanzapine is described.. A 69-year-old woman came to the emergency department after four days of experiencing epigastric pressurelike pain that radiated to the left lower quadrant and worsened with ingestion of food. She had started lisinopril three months prior for treatment of hypertension and had been taking olanzapine regularly for bipolar disorder. Upon admission, she was afebrile and hemodynamically stable and exhibited tenderness of the epigastric region. Elevated pancreatic enzymes and abdominal computed tomography (CT) imaging findings confirmed the diagnosis of pancreatitis. Common causes of pancreatitis were ruled out, and it was determined that the recent combination of lisinopril and olanzapine was the likely cause. Food and liquids were withheld, and all oral medications were stopped at hospital admission. Her pain resolved completely after two days. She was discharged on hospital day 4, and all of her medications except lisinopril and olanzapine were resumed. During a follow-up visit with her primary care physician, she reported to be doing well and had no systemic complaints. Olanzapine was reinitiated at that time but was discontinued a month later by her psychiatrist, who was concerned about the development of recurrent symptoms of pancreatitis. Valsartan was prescribed to achieve optimal blood pressure control three weeks after discharge. A follow-up CT scan of the abdomen a month later found no residual pancreatic abnormalities.. The additive effect of two known pancreatitis-causing medications resulted in increased risk and subsequent acute pancreatitis in this patient.

Topics: Acute Disease; Aged; Angiotensin-Converting Enzyme Inhibitors; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Interactions; Drug Therapy, Combination; Female; Humans; Hypertension; Lisinopril; Olanzapine; Pancreatitis

Bipolar illness is associated with significant psychosocial morbidity and health resource utilization. Second generation antipsychotics, used alone or in combination with mood stabilizers are effective in treating acute mania in community settings. This study was designed to compare the change in clinical parameters and resource utilization at one month in a group of patients who required treatment intervention for exacerbation of mania. The clinical response at one year was also evaluated.. 496 patients were enrolled at 75 psychiatric practices across Canada. The Olanzapine cohort (n = 287) included patients who had olanzapine added to their medication regimen or the dose of olanzapine increased. The Other cohort (n = 209) had a medication other than olanzapine added or the dose adjusted. Changes from baseline in the Young Mania Rating Scale (YMRS), Montgomery Asberg Depression Rating Scale, Beck Anxiety Inventory and SF-12 Health Survey were compared at one month using ANCOVA. Categorical variables at one month for health resource utilization, employment status, abuse/dependency, and the number of suicide attempts were compared using Fisher's Exact test. Patients were followed for one year and a subgroup was evaluated.. At one month, patients in the Olanzapine cohort recorded a mean reduction in the YMRS of 11.5, significantly greater than the mean reduction in the Other cohort of 9.7 (ANCOVA P = 0.002). The Olanzapine cohort was significantly improved compared to the Other cohort on the scales for depression and anxiety and did not experience the deterioration in physical functioning seen in the Other cohort. No significant differences were detected in health-related quality-of-life measures, employment status, drug abuse/dependency, number of suicide attempts, mental functioning, emergency room visits or inpatient psychiatric hospitalizations. In a subgroup treated for 12 months with a single second generation antipsychotic, improvements in illness severity measures were maintained with no evidence of significant differences among the antipsychotics.. Patients with bipolar disorder requiring treatment intervention for exacerbation of mania in the community setting responded to olanzapine at one month. In a subset analysis, second generation antipsychotic treatment continued to be beneficial in reducing bipolar symptoms at one year.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Canada; Cohort Studies; Community Mental Health Services; Data Collection; Female; Follow-Up Studies; Health Services; Health Status; Humans; Male; Olanzapine; Personality Inventory; Psychiatric Status Rating Scales; Severity of Illness Index; Suicide, Attempted; Surveys and Questionnaires; Treatment Outcome

We report the case of a 29-year-old man, who could not remember some words of Kanji and showed emotional instability. Magnetic resonance imaging (MRI) scan of his brain appeared normal. Cerebrospinal fluid (CSF) analysis showed lymphocytic pleocytosis. An electroencephalogram (EEG) showed slow activities in both frontal regions of the brain. He was diagnosed as acute encephalitis. On his fourth hospital day, he was found to be catatonic and showed mutism, akinetism, and catalepsy. On the ninth day, he showed hyperpyrexia, muscle rigidity, difficulty in swallowing, respiratory insufficiency, and rhabdomyolysis (creatine phosphokinase (CK), 3038 IU/l). He was diagnosed as malignant catatonia. Intravenous administration of acyclovir, high-dose methylprednisolone, antibiotics, diazepam, and dantrolene sodium was not effective. After initiating oral administration of olanzapine, his condition improved.

Topics: Acute Disease; Administration, Oral; Adult; Antipsychotic Agents; Benzodiazepines; Catatonia; Electroencephalography; Encephalitis; Humans; Male; Olanzapine; Treatment Outcome

Acute psychosis is diagnosed by clearly defined operational criteria embedded into international classification systems. Many studies have tried to determine the role of gender in psychosis but mainly in terms of epidemiology and course of illness, most often schizophrenia. There are however also important gender-specific differences in clinical symptoms of acute psychosis. No guidelines or treatment recommendations suggest gender as an important factor in the choice of antipsychotic treatment, which is true for all treatment modalities (antipsychotic, dose, duration). We will review shortly available literature and present some of our own research data on gender differences in clinical presentations of acute psychosis. When the diagnosis of an illness depends almost entirely on symptoms and their presentations as in the case of acute psychosis, important gender specific differences might challenge the diagnostic process as well as treatment choice and course of psychosis. Our as well as other data confirm that acute psychosis manifest itself differently in males and females. To define further the impact of observed differences we need further research into gender specific clinical and not just epidemiological variables.

Topics: Acute Disease; Adult; Affect; Amisulpride; Antipsychotic Agents; Benzodiazepines; Brain; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Hospitalization; Humans; Internal-External Control; Male; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Sex Factors; Sulpiride; Thinking

Acute mania requires hospitalization and prompt control of symptoms. The aim of this study was to compare the efficacy of sodium valproate and olanzapine administered alone or in combination in patients suffering from acute mania. Patients (N = 30) suffering from acute mania were divided into two equal groups. Group 1 patients were treated with sodium valproate 250 mg 3 times a day and Group 2 patients received olanzapine 5 mg twice daily. In both groups sodium valproate or olanzapine was given as add-on therapy at 3 weeks. The primary method of assessment was 50% or more improvement on the Young Mania Rating Scale (YMRS). The serum levels of valproic acid were also measured. Sodium valproate and olanzapine were effective in the treatment of acute mania with all patients demonstrating a 50% or more improvement on the YMRS. Sodium valproate-treated patients receiving olanzapine in the third week had a 15.3% decrease in the YMRS score and patients on olanzapine receiving sodium valproate had a 23.7% decrease. Patients who attained serum valproic acid levels of 100 μg/mL showed improvement on the YMRS. The present study supports combination therapy in the management of acute mania and suggests that serum valproic acid levels of 100 microg/mL are necessary for clinical response.

Topics: Acute Disease; Adult; Aged; Benzodiazepines; Bipolar Disorder; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Olanzapine; Prospective Studies; Valproic Acid

To compare the effectiveness of intramuscular (IM) olanzapine and typical IM antipsychotics in naturalistically treated acutely agitated patients with schizophrenia or acute mania.. During the acute phase, 2011 inpatients (including emergency settings) were assessed at 2, 24 and 72 h, and 7 days following initial injection and on oral antipsychotic transition. Mean change in agitation was assessed via Positive and Negative Symptom Scale-Excited Component (PANSS-EC) and Clinical Global Impressions-Severity (CGI-S) scores. Response (> or = 40% reduction in baseline PANSS-EC score) was analysed using logistic regression.. Significantly greater decreases in PANSS-EC and CGI-S scores were observed in patients receiving IM olanzapine (n = 1294) as their first injection compared with patients receiving other IM antipsychotics (n = 717) (P<0.05; 2 h: effect size 0.1); IM haloperidol treatment (all assessments, P<0.05); and IM zuclopenthixol treatment (2 h, P<0.001). Higher response rates were observed with IM olanzapine compared with other IM antipsychotics at 24 and 72 h, and 7 days (P<0.05). IM olanzapine was associated with fewer extrapyramidal side effects compared with other assessed IM antipsychotics.. IM olanzapine provided somewhat more effective control of acute agitation than other assessed IM antipsychotics.

Topics: Acute Disease; Administration, Oral; Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Bipolar Disorder; Clopenthixol; Cross-Cultural Comparison; Female; Haloperidol; Hospitalization; Humans; Injections, Intramuscular; Male; Olanzapine; Psychiatric Status Rating Scales; Psychomotor Agitation; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Race is strongly associated with risk for metabolic dysfunction, but there is limited prospective data concerning the impact of race on antipsychotic metabolic outcomes among patients with schizophrenia.. This study is a post hoc analysis of data from a 26-week, double-blind, randomized trial of aripiprazole (N = 155) and olanzapine (N = 159) conducted from April 2000 through June 2001 in patients aged >or= 18 years with acute schizophrenia according to DSM-IV criteria. The data were analyzed on the basis of racial breakdown: white and black/Hispanic. Between-drug and within-drug outcomes were analyzed separately for each racial cohort across weight, lipid, and glucose parameters.. For white subjects (N = 167), olanzapine significantly worsened all metabolic parameters except high-density lipoprotein (HDL) cholesterol and fasting glucose, and this was significantly different than aripiprazole for every outcome except fasting glucose. In the black/Hispanic cohort (N = 137), olanzapine treatment resulted in adverse metabolic outcomes, and these changes were significantly different from aripiprazole for adiposity, total cholesterol, and non-HDL cholesterol. Aripiprazole decreased the odds of endpoint metabolic syndrome compared with olanzapine for all subjects (OR = 0.33, 95% CI = 0.19 to 0.55), the white cohort (OR = 0.20, 95% CI = 0.10 to 0.41), and black/Hispanic subjects (OR = 0.53, 95% CI = 0.25 to 1.12), but the black/Hispanic result was not statistically significant (p = .096). Within the aripiprazole group, white subjects had significantly lower risk for metabolic syndrome, but there was no significant difference in metabolic syndrome between white and black/Hispanic subjects exposed to olanzapine.. Race may be an important moderator of metabolic risk during atypical antipsychotic therapy. Olanzapine treatment is associated with greater effects on adiposity and lipids than aripiprazole in both white and black/Hispanic subjects, suggesting that antipsychotic choice and intensive monitoring are important in minimizing metabolic risk, especially in nonwhite patients.

Topics: Acute Disease; Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Black or African American; Blood Glucose; Body Weight; Cholesterol, HDL; Cholesterol, LDL; Double-Blind Method; Female; Hispanic or Latino; Humans; Hypercholesterolemia; Male; Metabolic Syndrome; Middle Aged; Obesity; Olanzapine; Piperazines; Quinolones; Randomized Controlled Trials as Topic; White People; Young Adult

This study compared the safety, tolerability and switch to oral medication in patients with bipolar disorder or schizophrenia who received intramuscular (IM) olanzapine or other IM antipsychotics for the treatment of acute agitation.. Patients (N = 2011) from 15 countries participated in this prospective, observational, non-interventional study. Inpatients requiring treatment with at least one IM injection of a short-acting antipsychotic were assessed at baseline and within 7 days after the first IM injection. Treatment groups comprised: (i) patients prescribed IM olanzapine at baseline; and (ii) patients prescribed any other IM antipsychotic medication at baseline. Outcome measures included: treatment-emergent adverse events, concomitant psychotropic medication and the time taken to switch to oral medication.. Fewer patients in the IM olanzapine group experienced an adverse event than patients in the other IM antipsychotic group (34.4% vs. 46.2%, p < 0.001). The most frequently reported adverse events in both groups were: sedation, Parkinsonism, disturbance in attention, akathisia, dystonia and orthostatic hypotension. Fewer patients in the IM olanzapine group used anticholinergics (13.9% vs. 42.5%, p < 0.001) or anxiolytics/hypnotics (47.6% vs. 51.6%, p = 0.023). Patients in the IM olanzapine group switched to oral medication earlier than patients in the other IM antipsychotic group (median time = 46.5 vs. 48.0 h, p = 0.009).. These findings suggest that IM olanzapine may have a favourable impact on individual patients. However, the high rate of oral concomitant medication used throughout the study limits these findings from being associated with IM olanzapine alone.

Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Olanzapine; Restraint, Physical; Schizophrenia; Treatment Outcome; Young Adult

Topics: Acute Disease; Benzodiazepines; Female; Humans; Meige Syndrome; Middle Aged; Olanzapine

To investigate prescribing patterns for antipsychotic regimens based on intramuscular haloperidol or intramuscular olanzapine for treating acute agitation; to compare the costs of each drug regimen, which included adjunctive anxiolytics and/or anticholinergics; and to compare the effectiveness and safety of each drug regimen.. Retrospective medical record review.. State psychiatric facility.. Twenty-seven patients who received intramuscular haloperidol to treat 47 episodes of acute agitation and 26 patients who received intramuscular olanzapine to treat 38 episodes.. Data from patients receiving the antipsychotic regimens between August 2004 and March 2007 were reviewed. Mean +/- SD doses were 6.4 +/- 2.4 mg (range 2.5-10 mg) for haloperidol and 8.1 +/- 2.3 mg (range 5-10 mg) for olanzapine. The mean +/- SD cost of treating an episode of agitation with haloperidol was significantly lower at $4.06 +/- 3.98 (range $1.74-18.35) versus $27.84 +/- 10.40 (range $21.58-52.46) for olanzapine (p<0.0001). Significantly fewer patients who received haloperidol than patients who received olanzapine required additional pharmacotherapy to manage agitation (41% vs 69%, chi(2)=4.34, p=0.04). No significant differences were found between groups in the mean number of repeat doses of psychotropic drugs needed/episode (0.6 [range 0-5] for haloperidol vs 0.8 [range 0-3] for olanzapine, p=0.47), in the percentages of patients who required seclusion and/or restraints (59% for haloperidol vs 58% for olanzapine, chi(2)=0.01, p=0.91), or in time spent in seclusion and/or restraints (3.7 +/- 7.1 for haloperidol vs 3.6 +/- 6.5 hrs for olanzapine, p=0.92). No adverse events were documented with either drug.. For the treatment of acute episodes of agitation, regimens based on intramuscular haloperidol were significantly less expensive than and at least as effective as those based on intramuscular olanzapine.

Topics: Acute Disease; Adult; Anti-Anxiety Agents; Antipsychotic Agents; Benzodiazepines; Cholinergic Antagonists; Cohort Studies; Combined Modality Therapy; Drug Costs; Female; Haloperidol; Humans; Injections, Intramuscular; Male; Olanzapine; Patient Isolation; Practice Patterns, Physicians'; Psychomotor Agitation; Restraint, Physical; Time Factors

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Humans; Male; Olanzapine; Pancreatitis

Investigations with the use of the Calgary Depression scale for schizophrenia and standardized psychometric scales revealed depression in the acute psychotic phase of the disease in 198 patients and depressive syndrome in 148 ones in the postpsychotic phase. The phase of schizophrenia (acute or postpsychotic) influenced the choice of antidepressive therapy. Depressive syndrome during the acute phase of schizophrenia was the integral part of a psychotic episode. Manifestations of depressive symptoms correlated with the severity of positive symptoms. Depression was responsive to antipsychotic monotherapy using conventional and unconventional agents. Depression with adynamic symptoms was especially frequent in the postpsychotic phase of schizophrenia. Depressions usually developed after the first episode of schizophrenia. Those observed immediately after a psychotic episode differed from depressions following prolonged therapy. The structure of depressive syndrome was influenced by the number of previous psychotic episodes The combination of antipsychotics and antidepressants was effective in the treatment of depressive symptoms in schizophrenic patients during the postpsychotic phase. The presence of depression in case of proper therapy is not a predictor of poor prognosis. Recognition and adequate treatment of depression in schizophrenia require greater attention. Optimized control of mood disorders accompanying schizophrenia increases the possibility to improve the clinical outcome.

Topics: Acute Disease; Adult; Antidepressive Agents, Tricyclic; Antipsychotic Agents; Benzodiazepines; Chi-Square Distribution; Data Interpretation, Statistical; Depressive Disorder; Drug Therapy, Combination; Female; Haloperidol; Humans; Male; Olanzapine; Psychometrics; Schizophrenia; Statistics, Nonparametric; Treatment Outcome

To evaluate the 12-week outcomes (effectiveness, tolerability, and patterns of medication use) of olanzapine (either in antimanic monotherapy or in combination with other antipsychotics, anticonvulsants, and/or lithium) in patients with bipolar mania or mixed mania.. EMBLEM (European Mania in Bipolar Longitudinal Evaluation of Medication) is a 24-month prospective observational study of in- and outpatients with acute mania/mixed mania conducted in 14 European countries. Primary outcome measures included Clinical Global Impressions-Bipolar Disorder scale (overall, mania, and depression); 5-item Hamilton Depression Rating Scale; and Young Mania Rating Scale. Tolerability measures included a questionnaire to assess patients' symptomatic complaints.. Overall, 2004 patients received olanzapine (olanzapine monotherapy, n=673; olanzapine combination, n=1331). Concomitant therapy with antidepressants and/or anxiolytics was possible in both groups. The countries significantly differed in the use of olanzapine monotherapy versus olanzapine combination (p<.0001). Baseline-to-endpoint changes on the CGI-BP subscales, YMRS, and HAMD-5 were significant within both treatment groups (p<.0001). Olanzapine monotherapy was generally better tolerated than olanzapine combination, particularly with regard to sedation (12% vs 17%; p<.001), tremor (2% vs 5%; p<.001), and akathisia (3% vs 6%; p<.001).. The acute-phase EMBLEM results suggest that in naturalistic settings, olanzapine (both as monotherapy and combination) may be effective in treating patients with bipolar mania. The use of olanzapine monotherapy or combination varies significantly across countries, but combination is generally the rule, rather than the exception.

Topics: Acute Disease; Adult; Ambulatory Care; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cross-Cultural Comparison; Dose-Response Relationship, Drug; Drug Therapy, Combination; Europe; Female; Follow-Up Studies; Humans; Lithium Carbonate; Longitudinal Studies; Male; Middle Aged; Olanzapine; Patient Admission; Prospective Studies; Psychiatric Status Rating Scales; Treatment Outcome

The true dose effect in flexible-dose clinical trials may be obscured and even reversed because dose and outcome are related.. To evaluate dose effect in response on primary efficacy scales from 2 randomized, double-blind, flexible-dose trials of patients with bipolar mania who received olanzapine (N = 234, 5-20 mg/day), or patients with schizophrenia who received olanzapine (N = 172, 10-20 mg/day), we used marginal structural models, inverse probability of treatment weighting (MSM, IPTW) methodology. Dose profiles for mean changes from baseline were evaluated using weighted MSM with a repeated measures model. To adjust for selection bias due to non-random dose assignment and dropouts, patient-specific time-dependent weights were determined as products of (i) stable weights based on inverse probability of receiving the sequence of dose assignments that was actually received by a patient up to given time multiplied by (ii) stable weights based on inverse probability of patient remaining on treatment by that time. Results were compared with those by unweighted analyses.. While the observed difference in efficacy scores for dose groups for the unweighted analysis strongly favored lower doses, the weighted analyses showed no strong dose effects and, in some cases, reversed the apparent "negative dose effect.". While naïve comparison of groups by last or modal dose in a flexible-dose trial may result in severely biased efficacy analyses, the MSM with IPTW estimators approach may be a valuable method of removing these biases and evaluating potential dose effect, which may prove useful for planning confirmatory trials.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Olanzapine; Probability; Psychotic Disorders; Randomized Controlled Trials as Topic; Research Design; Risperidone; Schizophrenia; Selection Bias; Treatment Outcome

To report the case of an 11-year-old girl who presented with acute onset of psychotic symptoms with catatonic features treated with electroconvulsive therapy (ECT).. Described herein is the case of an 11-year-old, prepubertal girl who represented with catatonic symptoms unresponsive to conventional medical treatment. After thorough clinical investigation and obtaining a second opinion we gained consent from her parents to perform ECT as a life saving procedure.. Six ECT treatments were administered with clinical improvement, the patient did develop hypomanic symptoms as a side-affect of ECT.. The patient exhibited potentially life-threatening self-harming behaviour secondary to catatonic and psychotic symptoms. Her behaviour and symptoms responded to ECT. The patient developed hypomania that responded to mood stabilization. ECT was a safe and effective treatment for catatonia in this prepubescent girl.

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Catatonia; Child; Electroconvulsive Therapy; Female; Hallucinations; Humans; Olanzapine

It clarifies a difference between early acute phase and late acute phase in medication.. The present report describes three patients with schizophrenia who presented with restlessness and excitement requiring hospitalization.. Treatment with risperidone solution orally or parenteral haloperidol until the day after admission, followed by olanzapine, successfully improved the clinical condition of the patients. In the early stage of hospitalization, selection of fast-acting drugs that can be administered to uncooperative patients is considered preferable, focusing on rapid control of symptoms and behavioral disorders, whereas after this early stage, olanzapine is preferable for improving patient compliance in addition to stabilizing symptoms.. Because the target symptoms differ between the early and late acute phases, the term 'acute phase' used in the broad sense should be divided into two units, each requiring a different therapeutic strategy, and independent clinical approaches should be considered in order to provide more suitable treatment.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Drug Therapy, Combination; Female; Follow-Up Studies; Gambling; Haloperidol; Humans; Japan; Male; Mental Disorders; Middle Aged; Olanzapine; Patient Admission; Patient Compliance; Risperidone; Schizophrenia, Disorganized; Schizophrenia, Paranoid; Treatment Outcome

Topics: Acute Disease; Antipsychotic Agents; Atrial Fibrillation; Benzodiazepines; Bipolar Disorder; Electrocardiography; Humans; Male; Middle Aged; Olanzapine

Although it is generally accepted that atypical antipsychotics differ in their risk for diabetic side effects, the underlying pharmacological mechanisms are unknown. Studies on the mechanisms of antipsychotic-induced hyperglycemia or insulin resistance are often confounded by the concomitant weight gain and dyslipidemia, known diabetic risk factors. To investigate whether antipsychotics can acutely cause metabolic effects before any change in body composition, we studied the effects of four atypical antipsychotics on whole-body insulin resistance. Using the hyperinsulinemic, euglycemic clamp technique in conscious rats, insulin and somatostatin were infused at a constant rate to provide constant hyperinsulinemia and to suppress pancreatic insulin secretion. Glucose was infused at a variable rate, adjusted to maintain euglycemia. At steady state, animals were administered vehicle (V) or antipsychotic and the glucose infusion rate was monitored as an index of insulin sensitivity. Clamp experiments using radiotracers and studies on glucose uptake into isolated skeletal muscle were conducted to differentiate between effects on hepatic glucose production (HGP) and on peripheral glucose uptake. Olanzapine (OLAN) and clozapine (CLOZ) acutely impaired whole-body insulin sensitivity in a dose-dependent manner (P<0.001 vs V), whereas ziprasidone and risperidone had no effect. CLOZ also induced profound insulin resistance after dosing 10 mg/kg/day for 5 days (P<0.05 vs V). Tracer studies indicated that acute changes mainly reflect increased HGP, consistent with the lack of effect on glucose uptake. OLAN and CLOZ can thus rapidly induce marked insulin resistance, which could contribute to the hyperglycemia and ketoacidosis reported for patients receiving those therapies.

Topics: Acute Disease; Animals; Antipsychotic Agents; Benzodiazepines; Clozapine; Disease Models, Animal; Dose-Response Relationship, Drug; Energy Metabolism; Glucose; Hyperglycemia; Insulin; Insulin Resistance; Liver; Male; Metabolic Syndrome; Muscle, Skeletal; Olanzapine; Rats; Rats, Wistar; Somatostatin

Recent volumetric magnetic resonance imaging (MRI) studies have suggested brain volume changes in schizophrenia to be progressive in nature. Whether this is a global process or some brain areas are more affected than others is not known. In a 5-year longitudinal study, MRI whole brain scans were obtained from 96 patients with schizophrenia and 113 matched healthy comparison subjects. Changes over time in focal gray and white matter were measured with voxel-based morphometry throughout the brain. Over the 5-year interval, excessive decreases in gray matter density were found in patients in the left superior frontal area (Brodmann areas 9/10), left superior temporal gyrus (Brodmann area 42), right caudate nucleus, and right thalamus as compared to healthy individuals. Excessive gray matter density decrease in the superior frontal gray matter was related to increased number of hospitalizations, whereas a higher cumulative dose of clozapine and olanzapine during the scan interval was related to lesser decreases in this area. In conclusion, gray matter density loss occurs across the course of the illness in schizophrenia, predominantly in left frontal and temporal cortices. Moreover, the progression in left frontal density loss appears to be related to an increased number of psychotic episodes, with atypical antipsychotic medication attenuating these changes.

Topics: Acute Disease; Adolescent; Adult; Antipsychotic Agents; Atrophy; Benzodiazepines; Brain; Caudate Nucleus; Clozapine; Disease Progression; Female; Follow-Up Studies; Frontal Lobe; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Middle Aged; Olanzapine; Schizophrenia; Temporal Lobe; Thalamus; Time Factors

Humoral and cellular immunological parameters were studied in 59 schizophrenic patients and 38 healthy subjects. It was demonstrated that high level of circulating immune complexes is characteristic of the acute state (a relapse) of schizophrenia. The level of this parameter was higher in patients before treatment vs. healthy controls; after therapy with olanzapine this level decreased and did not differ from that of controls. The functional activity of immunocompetent cells (the phagocyte activity of neutrophiles and monocytes, the cytotoxic activity of natural killer lymphocytes, interleukin-2, and interleukin-10 production) did not depend on the clinical condition of the patients and the therapy and was significantly lower than that of controls both before and during the treatment. Attention should be paid to the fact that the level of IL-1beta production in schizophrenia patients did not differ from that of controls. After eight weeks of therapy the level of IL-1beta production increased significantly in all groups of patients and was significantly higher than that of controls during the whole observation period irrespectively of sex and patients' response to the therapy.

Topics: Acute Disease; Adolescent; Adult; Antigen-Antibody Complex; Antipsychotic Agents; Benzodiazepines; Cytotoxicity, Immunologic; Data Interpretation, Statistical; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-1beta; Male; Middle Aged; Olanzapine; Recurrence; Schizophrenia; Time Factors; Treatment Outcome

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Chylomicrons; Humans; Male; Olanzapine; Pancreatitis; Psychotic Disorders

Topics: Acute Disease; Acute Kidney Injury; Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Cocaine-Related Disorders; Diabetic Ketoacidosis; Humans; Male; Olanzapine; Pancreatitis; Piperazines; Quinolones; Schizophrenia

Neuroleptic malignant syndrome (NMS) is the most serious of acute neurological side effects produced by antipsychotic medication, characterized by hyperthermia, rigidity, altered consciousness and autonomic dysfunction, the prevalence of which varies from 0.4-1.4%. NMS is usually seen in treatment with high potency typical antipsychotics and very rarely with atypical antipsychotics. However, NMS cases have been reported with risperidone, clozapine, olanzapine and quetiapine. The presentations of NMS have often varied and we report another atypicality in presentation of NMS due to olanzapine use.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Humans; Male; Neuroleptic Malignant Syndrome; Olanzapine

Metabolic syndrome is a strong determinant of new-onset diabetes and coronary heart disease in general populations. Given the higher prevalence of metabolic syndrome among mentally ill patients, the syndrome poses a greater health risk to this population. Atypical antipsychotic treatment may exacerbate this condition. We compared both the rate and incidence of metabolic syndrome among schizophrenia patients (DSM-IV criteria) treated with the atypical antipsychotics aripiprazole or olanzapine or placebo from 4 double-blind, randomized, controlled clinical trials.. Metabolic syndrome was defined according to the Third Adult Treatment Panel (ATP III) Guidelines as the presence on follow-up of 3 of the following abnormalities: waist circumference > 102 cm if male and > 88 cm if female, high density lipoprotein (HDL) < 40 mg/dL if male and < 50 mg/dL if female, diastolic blood pressure >or= 85 mm Hg or systolic blood pressure >or= 130 mm Hg, fasting triglycerides >or= 150 mg/dL, fasting plasma glucose >or= 110 mg/dL. Both the rate of metabolic syndrome and the person-time incidence were computed from the on-treatment follow-up.. In the placebo-controlled trials, the rate of metabolic syndrome was 25.8% among 155 placebo patients and 19.9% for 267 aripiprazole patients (p = .466 by stratified log rank). The incidence of metabolic syndrome was 14.3% for 91 placebo patients versus 5.3% for 151 aripiprazole patients (p < .001). In the active comparator trials, patients treated with olanzapine (N = 373) versus aripiprazole (N = 380) exhibited rates of 41.6% and 27.9%, respectively (p = .0002). Incidence rates were 27.4% for 212 olanzapine patients versus 15.7% for 198 aripiprazole patients (p = .0055).. Both the rate and incidence of clinically relevant metabolic syndrome differ according to the choice of antipsychotic agent. The association between metabolic syndrome and treatment warrants careful consideration in the choice of antipsychotic agents.

Topics: Acute Disease; Adult; Anthropometry; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Cholesterol, HDL; Drug Administration Schedule; Female; Humans; Hyperlipidemias; Hypertension; Incidence; Male; Metabolic Syndrome; Olanzapine; Piperazines; Prevalence; Quinolones; Schizophrenia

Atypical antipsychotics are commonly used to treat behavioral disturbances in elderly demented patients. However, recent data have brought the tolerability of these drugs into question, as the majority of them have been associated with an increased risk for cerebrovascular events and death in this population. Specifically, increased risk has been found with olanzapine, aripiprazole, risperidone, and quetiapine. The other 2 atypical anti- psychotics, clozapine and ziprasidone, have not been studied in elderly populations. Although these medications are all classified as atypical antipsychotics, they exert varying degrees of blockade at dopamine, muscarinic, histaminic, and adrenergic receptors. Among these drugs, olanzapine has the greatest affinity for muscarinic receptors and, hence, may be associated with a greater risk for anticholinergic effects, including urinary retention.. The aim of this report was to discuss the possibility that administration of olanzapine may provoke acute urinary retention (AUR) in some patients.. We describe the development of AUR leading to acute renal failure subsequent to olanzapine administration in 2 geriatric patients with benign prostatic hypertrophy (BPH).. Given the cases presented, we recommend that clinicians measure electrolytes, blood urea nitrogen, and creatinine every 2 or 3 days for 1 or 2 weeks after initiating olanzapine treatment and after each dose increase. This is especially important for cognitively impaired elderly patients with BPH, as they may not be able to provide clear feedback regarding adverse effects of the medication.

Topics: Acute Disease; Acute Kidney Injury; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Blood Urea Nitrogen; Creatinine; Drug Monitoring; Electrolytes; Humans; Male; Olanzapine; Prostatic Hyperplasia; Receptors, Muscarinic; Urinary Retention

This prospective observational study examined the outcomes associated with the treatment of bipolar mania in clinical practice settings in a diverse range of countries: Bosnia, Slovenia, Slovakia, Egypt, Saudi Arabia and Turkey. Particular emphasis was placed on investigating outcomes associated with treatment regimens including and excluding the atypical antipsychotic olanzapine.. In- and outpatients initiating or changing oral medication for the treatment of bipolar mania were grouped into two treatment cohorts: (1) olanzapine (N=569), and (2) non-olanzapine (N=325). Clinical outcome measures included change in Clinical Global Impressions-Bipolar Version Severity of Illness scale (CGI-BP), Young Mania Rating Scale (YMRS) and Hamilton Depression Rating scale- 5 item (HAMD-5) scores, and response and remission rates. Outcomes were analysed by conventional linear or logistic regression, adjusted for potential confounders, using last observation carried forward (LOCF) at endpoint, and a marginal structural model (MSM) approach to account for treatment switching. Results from the 12-week acute phase are presented.. Clinical improvements were observed in both cohorts. While no marked differences were apparent between the groups in adjusted mean baseline to LOCF endpoint change, longitudinal analysis of these variables using MSM averaged over all visits indicated greater improvements in the olanzapine versus non-olanzapine cohort in CGI-BP Overall (-0.26, p<0.001), CGI-BP Mania (-0.19, p<0.001), CGI-BP Depression (-0.10, p=0.003), CGI Psychosis (-0.14, p=0.001), YMRS (-1.70, p<0.001), and HAMD-5 (-0.40, p<0.001) scores.. Inclusion of olanzapine after initiating or switching treatment for bipolar mania appeared to be beneficial during treatment in terms of symptom improvement.

Topics: Acute Disease; Administration, Oral; Adult; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cohort Studies; Cross-Cultural Comparison; Drug Therapy, Combination; Drug Utilization; Female; Humans; Long-Term Care; Male; Middle Aged; Olanzapine; Personality Inventory; Prospective Studies; Psychiatric Status Rating Scales; Treatment Outcome

We report a case of recurrent psychosis, spanning decades, with full inter-episode recovery and minimal functional impairment. While it is difficult to classify this disorder using DSM IV-TR criteria, Leonhard and others have described a 'cycloid psychosis' that correlates well with the phenomenology and course of this case. We believe this may represent a subset within the ICD-10 category of 'acute and transient psychotic disorders'. While this disorder, of unknown incidence, is not well reported in the U.S., it is worthy of further investigation and clinical attention given its generally favorable prognosis and potentially distinct pathophysiology and treatment.

Topics: Acute Disease; Aged; Benzodiazepines; Cognition Disorders; Delusions; Diagnosis, Differential; Diagnostic and Statistical Manual of Mental Disorders; Drug Therapy, Combination; Hallucinations; Hospitalization; Humans; Lorazepam; Male; Olanzapine; Psychomotor Agitation; Psychotic Disorders; Recurrence

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Clinical Trials, Phase I as Topic; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Humans; Olanzapine; Patient Dropouts; Perphenazine; Randomized Controlled Trials as Topic; Schizophrenia; Treatment Outcome

The patient with acute extrapyramidal signs and symptoms presents a significant clinical challenge. We present the case of a young man who developed an acute akathisia and dystonia after inadvertent overdose of olanzapine (Zyprexa) in the setting of a recent discontinuation of fluoxetine. The receptor chemistry and mechanisms pertinent to his presentation are reviewed. An analysis of the literature indicates that a broad incidence range is cited for the extrapyramidal effects of these medications. We suggest a diagnostic and therapeutic approach to the undifferentiated patient presenting with extrapyramidal signs and symptoms. The possibility of neuroleptic malignant syndrome (NMS), serotonin syndrome (SS), tricyclic overdose, and cocaine abuse should be considered in a patient with extrapyramidal signs and symptoms, given the potential for complications. An emphasis is placed on the need for carefully verbalized discharge instructions to avoid a potential untoward outcome.

Topics: Accidents; Acute Disease; Adult; Akathisia, Drug-Induced; Benzodiazepines; Drug Overdose; Dystonia; Emergency Service, Hospital; Fluoxetine; Humans; Male; Olanzapine; Selective Serotonin Reuptake Inhibitors

Topics: Acute Disease; Adolescent; Aged; Antipsychotic Agents; Benzodiazepines; Dermatologic Agents; Female; Humans; Middle Aged; Olanzapine; Prurigo

The case of a 56 years old man is presented, who developed acute generalized exanthematous pustulosis 5 days after the introduction of olanzapine 10 mg. Multiple 1-mm pustules appeared on the whole body, concentrated especially on her neck and face. Within 2 days, the eruption was increasingly accompanied by erythema and pruritus. No fever, chills, nausea, vomiting, arthralgias or myalgias were recorded. The diagnosis was corroborated by hystopathology. After 7 days of treatment, olanzapine and valproate were stopped. Concomitantly, cetirizine 20 mg p.o. and methylprednisolone 500 mg i.v. were given once. During the following week betamethasone cream was applied, and the pustular eruption resolved completely.

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Drug Eruptions; Exanthema; Female; Humans; Middle Aged; Olanzapine; Skin Diseases, Vesiculobullous

In 2005, the Canadian Network for Mood and Anxiety Treatments (CANMAT) published guidelines for the management of bipolar disorder. This update reviews new evidence since the previous publication and incorporates recommendations based on the most current evidence for treatment of various phases of bipolar disorder. It is designed to be used in conjunction with the 2005 CANMAT Guidelines. The recommendations for the management of acute mania remain mostly unchanged. Lithium, valproate and several atypical antipsychotics continue to be recommended as first-line treatments for acute mania. For the management of bipolar depression, new data support quetiapine monotherapy as a first-line option. Lithium and lamotrigine monotherapy, olanzapine plus selective serotonin reuptake inhibitors (SSRI), and lithium or divalproex plus SSRI/bupropion continue to remain the other first-line options. First-line options in the maintenance treatment of bipolar disorder continue to be lithium, lamotrigine, valproate and olanzapine. There is recent evidence to support the combination of olanzapine and fluoxetine as a second-line maintenance therapy for bipolar depression. New data also support quetiapine monotherapy as a second-line option for the management of acute bipolar II depression. The importance of comorbid psychiatric and medical conditions cannot be understated, and this update provides an expanded look at the prevalence, impact and management of comorbid conditions in patients with bipolar disorder.

Topics: Acute Disease; Antidepressive Agents; Antipsychotic Agents; Anxiety Disorders; Benzodiazepines; Bipolar Disorder; Canada; Comorbidity; Dibenzothiazepines; Drug Therapy, Combination; Humans; Lamotrigine; Lithium Carbonate; Mood Disorders; Olanzapine; Quetiapine Fumarate; Triazines; Valproic Acid

Akathisia is a clinical important symptom, frequently induced by neuroleptic treatment. Despite its clinical importance, less is known about its pathophysiology.. Using [18]-FDG-PET, imaging patterns of cortical metabolic activity were obtained in a patient during olanzapine-induced akathisia and after recovery.. Akathisia was characterized by a reduced metabolic activity in thalamus and cerebellum. After discontinuing medication akathisia disappeared, reflected by a recovery of metabolic activity in these brain areas.. [18]-FDG-PET may be useful to identify cortical regions mediating clinical aspects of drug-induced akathisia, thereby offering a deeper insight into the pathophysiology of this serious side effect.

Topics: Acute Disease; Akathisia, Drug-Induced; Antipsychotic Agents; Benzodiazepines; Cerebellum; Fluorodeoxyglucose F18; Humans; Male; Middle Aged; Olanzapine; Positron-Emission Tomography; Radiopharmaceuticals; Schizophrenia; Thalamus

The aim of this study was to compare the efficacy and safety of intramuscular ziprasidone versus intramuscular (i.m.) olanzapine in treating aggression in youth.. A retrospective chart review of 100 hospitalized patients less than 18 years of age treated with either i.m. ziprasidone or i.m. olanzapine for agitation or aggression was conducted. Comparisons were performed using statistical analysis of data collected from medical records.. Baseline demographics were similar in the i.m. olanzapine and ziprasidone treatment groups regarding age and ethnicity; however, gender differences did reach statistical significance (p < 0.001). Dosing between children and adolescents significantly differed in the olanzapine group, whereas dosing was comparable in the ziprasidone group. No significant differences between the olanzapine and ziprasidone treatment groups were noted regarding length of stay, efficacy of the study medications, number of restraints, and duration of restraints. Ziprasidone subjects received significantly more doses of emergency medication during their hospital stay and significantly more doses of ziprasidone were administered with concomitant lorazepam or antihistamines.. The results suggest i.m. ziprasidone and intramuscular olanzapine may be equally effective in treating aggression in youth. These agents may also be similar with regard to safety because no clinically significant adverse events were reported for either treatment group. The possibility of poor documentation of adverse events and side effects prevents formulating definitive conclusions regarding safety from this study.

Topics: Acute Disease; Adolescent; Aggression; Antipsychotic Agents; Benzodiazepines; Child; Ethnicity; Female; Humans; Injections, Intramuscular; Inpatients; Male; Olanzapine; Piperazines; Psychomotor Agitation; Retrospective Studies; Sex Characteristics; Thiazoles; Treatment Outcome

Olanzapine is an atypical antipsychotic that is reported to cause myopathy and raised creatine kinase (CK) levels. The prevalence and severity of acute myopathy after deliberate olanzapine ingestion are unclear. Therefore, we reviewed case notes from 64 consecutive patients admitted to our institution after olanzapine overdose. Overall, serum CK was higher than five times the upper limit of normal in 17% of patients. The prevalence of raised CK values was positively correlated with the stated quantity of olanzapine ingested, suggesting a dose-dependent relationship for acute muscle toxicity. There was an apparent delay of 12 hours or more between olanzapine ingestion and the occurrence of maximum CK. Despite the high prevalence of acute muscle toxicity after olanzapine ingestion, none of the patients developed renal failure.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Creatine Kinase, MM Form; Dose-Response Relationship, Drug; Drug Overdose; Female; Humans; Male; Middle Aged; Muscle, Skeletal; Muscular Diseases; Olanzapine; Retrospective Studies; Rhabdomyolysis; Scotland

Reversible schizophrenia-like syndromes have been reported to occur with small-cell carcinoma of the lung, thymoma, and hematological disorders.. A 56-year-old man was admitted due to an acute psychosis characterized by delusions, agitation, and aggressive outbursts. His medical and psychiatric history was unremarkable. On treatment with olanzapine, valproic acid, and perazine there was only moderate improvement. Extensive checkup revealed an isolated mediastinal metastasis of an undifferentiated carcinoma. A primary tumor was not found. After removal of the metastasis, the psychosis remitted rapidly and completely, and the patient remained well on follow-up.. Paraneoplastic syndromes may clinically present as acute psychoses and, in late-onset schizophreniform disorders with an atypical presentation, performing a tumor search should always be considered.

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Humans; Male; Mediastinal Neoplasms; Middle Aged; Olanzapine; Paraneoplastic Syndromes, Nervous System; Perazine; Psychotic Disorders; Valproic Acid

This study assessed the safety and effectiveness of the atypical antipsychotic olanzapine for the treatment of inpatients with acute schizophrenia. Furthermore, we evaluated patterns of use of olanzapine and their relationship to safety and effectiveness.. This was a prospective, comparative, nonrandomized, open-label, observational study of 848 patients with schizophrenia (International Classification of Diseases, 10th edition) hospitalized due to an acute psychotic episode. Data were collected during patients' entire hospital stay. Safety of antipsychotic therapy was assessed with an extrapyramidal symptoms questionnaire (based on the Udvalg for Kliniske Undersøgelser scale) and the report of spontaneous adverse events. Clinical status was assessed with the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impressions-Severity of Illness (CGI-S). A multivariate statistical approach was employed.. Patients treated with olanzapine in monotherapy had the lowest risk of developing extrapyramidal symptoms (11.2%), whereas patients treated with conventional antipsychotics had a higher risk (39.0%; p < 0.001). Patients treated with olanzapine in monotherapy (even patients with prominent positive symptoms) displayed a higher rate of response compared with conventional antipsychotics-treated patients (p = .007).. Olanzapine is a safe and effective treatment for patients with acute schizophrenia in the hospital setting, even for patients with prominent positive or agitation symptoms.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Brief Psychiatric Rating Scale; Female; Hospitalization; Hospitals, Psychiatric; Humans; Male; Multivariate Analysis; Observation; Olanzapine; Prospective Studies; Schizophrenia; Severity of Illness Index; Social Environment

Despite the widespread use of the Brief Psychiatric Rating Scale (BPRS), the clinical meaning of its total score and cut-off values used to define treatment response are unclear.. To link the BPRS to Clinical Global Impression (CGI) ratings.. Equipercentile linking of BPRS and CGI ratings from seven drug trials in acutely ill patients with schizophrenia (n=1979).. 'Mildly ill' according to the CGI approximately corresponded to a BPRS total score of 31, 'moderately ill'to a BPRS score of 41 and'markedly ill'to a BPRS score of 53.'Minimally improved'according to the CGI score was associated with percentage BPRS reductions of 24, 27 and 30% at weeks 1, 2 and 4, respectively. The corresponding numbers for a CGI rating of 'much improved' were 44, 53 and 58%.. The results provide a clearer understanding of how to interpret BPRS total and percentage reduction scores in clinical trials with patients acutely ill with schizophrenia who are experiencing positive symptoms.

Topics: Acute Disease; Adult; Amisulpride; Antipsychotic Agents; Benzodiazepines; Female; Humans; Male; Olanzapine; Psychiatric Status Rating Scales; Schizophrenia; Severity of Illness Index; Sulpiride; Treatment Outcome

Olanzapine is a new atypical antipsychotic drug acting on different receptors. A variety of pharmacologic effects are responsible for toxicity and the variety of clinical symptoms seen in overdose: tachycardia, agitation or aggression, dysarthria, extrapyramidal dystonic effects, sedation or coma, small pupils, blurred vision, respiratory depression, hypotension. A retrospective analysis of clinical course of eight acute olanzapine intoxication treated at the Department of Clinical Toxicology Jagiellonian University Medical College is presented. CNS symptoms manifested in fluctuations between somnolence/coma and agitation/aggression and miosis were observed in most of the patients. Increased CPK activity was stated in the most of patients. All of the patients recovered, poisoning severity according PSS was moderate and severe.

Topics: Acute Disease; Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Drug Overdose; Female; Humans; Male; Nervous System Diseases; Olanzapine; Poisoning; Retrospective Studies; Severity of Illness Index

Cellular and humoral immunological parameters have been studied in 59 schizophrenic patients and 38 healthy controls. Immunological indices (CIC, autoantibodies to cardiolipin) were found to be significantly elevated in patients in the acute disease stage before the treatment. After olanzapin therapy, a level of these parameters decreased and did not differ from that of controls. In patients, irrespective of clinical condition and treatment, functional activity of immunocompetent cells (phagocyte activity of neutrophils and monocytes, cytotoxic activity of lymphocytes natural killers, interleukin-2, interleukin-10 and gamma-interferon production), was significantly lower both before the treatment as after therapy, i.e. did not change during the whole study (28 weeks). In responders, a level of IL-1B production was higher than in controls before and during the treatment. In non-responders, it was similar to that in controls before the therapy, and increased during the treatment to a higher level.

Topics: Acute Disease; Adolescent; Adult; Antipsychotic Agents; Autoantibodies; Benzodiazepines; Female; Humans; Interferon-gamma; Interleukin-1; Interleukin-10; Interleukin-2; Killer Cells, Natural; Lymphocytes; Male; Middle Aged; Monocytes; Neutrophils; Olanzapine; Phagocytes; Schizophrenia

Topics: Acute Disease; Adolescent; Antipsychotic Agents; Benzodiazepines; Brain; Cognition Disorders; Electroencephalography; Humans; Lamotrigine; Male; Neuropsychological Tests; Olanzapine; Recovery of Function; Schizophrenia; Severity of Illness Index; Triazines

This study analyzed the effect of olanzapine on a psychopathology-based scale assessing abnormal thought processes and examined the relationship between improvement on this scale and mania and depression improvement in acutely manic patients.. The study sample (N = 254) was pooled from two double-blind, randomized, placebo-controlled clinical trials. Disturbance in thought processes was measured by the Positive and Negative Symptom Scale cognitive component (PANSS-Cognitive) score. Mood severity was measured by the Young-Mania Rating Scale (Y-MRS) and Hamilton Depression Inventory (HAM-D). Last-observation-carried-forward (LOCF) changes from baseline to endpoint (Week 3) were presented for patients who had at least one post-baseline assessment.. Olanzapine-treated patients experienced modest but significant improvement in PANSS-Cognitive score (olanzapine: -4.25 n = 124; placebo: -1.69 n = 120, p < 01), regardless of age, gender, mania subtype (pure, mixed), course (rapid or non-rapid cycling), or the presence or absence of psychotic features. PANSS-Cognitive improvement was more highly correlated with mania than depression improvement.. Olanzapine improved abnormal thought processes measured by the PANSS-Cognitive score in patients with acute mania. This improvement in thought processes was significantly associated with improvement in acute mania. More sensitive and specific neuropsychological testing could help clarify whether improvement in thought processes on olanzapine was independent of mania reduction.

Topics: Acute Disease; Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cognition; Female; Humans; Male; Middle Aged; Multicenter Studies as Topic; Olanzapine; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic

Topics: Acute Disease; Adult; Benzodiazepines; Commitment of Mentally Ill; Female; Hospitalization; Humans; Length of Stay; Male; Olanzapine; Schizophrenia

Neuroleptic malignant syndrome (NMS) is an uncommon potentially fatal side effect of neuroleptic drugs, characterized by movement disorder, altered mental status and autonomic instability. A single dose of clotiapine was administered to an 11-year old male with acute psychosis. The previously healthy child had signs consistent with NMS including hyperthermia, hypertension, motor and mental changes. Repeat examination performed two weeks later, demonstrated that while his hyperthermia subsided, his mental status deteriorated. Olanzapine was administered, after which the child had hyperthermia, dystonia and more pronounced restlessness, once again consistent with NMS. He developed respiratory failure and was intubated and mechanically ventilated. Lorazepam, dantrolene and bromocriptine were administered as treatment of possible NMS. His mental condition, movement disorder and autonomic dysfunction improved significantly. Two weeks later, the patient was discharged in good general condition without the need for any ongoing medical treatment. There are only few case reports of NMS in children treated with olanzapine, an atypical antipsychotic. In children, caution must be exercised when prescribing antipsychotics, particularly atypical antipsychotics as these drugs may cause NMS. Because of the low incidence of NMS, a high index of suspicion is needed to identify cases so prompt treatment can be undertaken.

Topics: Acute Disease; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Blood Cell Count; Child; Dibenzothiazepines; Electroencephalography; False Positive Reactions; Humans; Magnetic Resonance Imaging; Male; Neuroleptic Malignant Syndrome; Neurologic Examination; Olanzapine; Phenytoin; Prion Diseases; Psychotic Disorders

A substantial number of patients with mania have significant concomitant depressive features, and they may respond differently to mood stabilizers than patients with pure mania. This post-hoc analysis explored the response characteristics of olanzapine versus placebo in bipolar I manic patients with dysphoric and nondysphoric mania (differentiated by baseline Hamilton Depression Rating Scale [HAM-D] score of >20). Two similar, double-blind, randomized trials comparing olanzapine, 5-20 mg, to placebo were pooled for these analyses (N = 246). Mean changes in Young-Mania Rating Scale (Y-MRS) and HAM-D scores during 3 weeks of treatment were examined. Twenty-eight percent of patients had dysphoric mania (olanzapine, n = 33; placebo, n = 35). Among these patients, olanzapine-treated patients had greater improvement within 1 week than did placebo-treated patients on both mania ratings (Y-MRS: -9.7 vs. -3.0 points; = 0.011) and depressive symptom ratings (HAM-D: -9.9 vs. -5.4 points; = 0.025). Among those manic subjects without prominent depressive symptoms (olanzapine, n = 91; placebo, n = 87), mean Y-MRS improvement from baseline to endpoint with olanzapine (-11.5 points) versus placebo (-6.13 points) was comparable to the improvement seen with olanzapine versus placebo in the dysphoric mania subgroup ( = 0.476, test of interaction). In acutely ill manic patients with significant depressive symptoms, olanzapine demonstrated a broad spectrum of efficacy, effectively treating both manic and depressive symptoms. The magnitude of the antimanic response appears similar, regardless of baseline depressive features. Additional experience with putative mood stabilizers and atypical agents in mixed mania should include an exploration of their efficacy in treating both manic and depressive mood symptoms.

Topics: Acute Disease; Affect; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Humans; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic; Treatment Outcome

The objective of this study was to determine if the orally disintegrating tablet formulation of olanzapine, Zyprexa Zydis, would facilitate antipsychotic medication compliance in acutely ill, non-compliant patients. Eighty-five acutely ill patients with schizophrenia or schizoaffective disorder who met medication non-compliance criteria received open-label olanzapine orally disintegrating tablets (1020 mgd) for up to 6 wk. Improvement in medication compliance was assessed using various rating scales to measure changes in psychopathology, medication-taking and compliance attitudes, and nursing care burden. Safety variables were also measured. Significant improvement from baseline was demonstrated in the Positive and Negative Syndrome Scale total score at Week 1 and subsequently (p0.001). Significant improvement from baseline was also seen in various scales measuring medication compliance, attitude, and nursing care burden (p0.05). Olanzapine orally disintegrating tablets were well-tolerated. Olanzapine orally disintegrating tablets may benefit acutely ill, non-compliant schizophrenic patients by facilitating acceptance of active antipsychotic drug therapy.

Topics: Acute Disease; Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Female; Humans; Male; Middle Aged; Olanzapine; Patient Compliance; Pirenzepine; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Solubility; Tablets; Treatment Outcome; Treatment Refusal

Hallervorden-Spatz disease is a rare autosomal recessive condition, with early onset of predominantly extrapyramidal dysfunction. The symptoms of the disease are dystonia, rigidity, choreoathetosis, pyramidal signs, and intellectual decline. Recent genetic studies mapped the disease to chromosome 20p12.3-p13, and identified mutations in the pantothenate kinase gene. This report describes a childhood onset case of Hallervorden-Spatz disease with schizophreniform psychotic symptoms. Former reports about the psychiatric comorbidity generally included depressive disorder.. A single case report.. A 14-year-old boy with Hallervorden-Spatz disease presented a psychotic episode with prominent auditory hallucinations. Symptoms were relieved after neuroleptic treatment.. To the authors' knowledge, this is the first published report of the disease with psychotic symptoms. The contribution of basal ganglia, with their wide projections, to the emergence of psychotic symptoms was discussed.

Topics: Acute Disease; Adolescent; Antipsychotic Agents; Benzodiazepines; Comorbidity; Dementia; Dominance, Cerebral; Globus Pallidus; Humans; Magnetic Resonance Imaging; Male; Neurologic Examination; Olanzapine; Pantothenate Kinase-Associated Neurodegeneration; Psychotic Disorders

Topics: Acute Disease; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Dopamine Antagonists; Drug Therapy, Combination; Haloperidol; Humans; Isotopes; Lithium; Olanzapine; Pirenzepine; Selective Serotonin Reuptake Inhibitors; Time Factors; Valproic Acid

Topics: Acute Disease; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Drug Therapy, Combination; Hospitalization; Humans; Isotopes; Lithium; Olanzapine; Patient Readmission; Pirenzepine; Placebos; Recurrence; Selective Serotonin Reuptake Inhibitors; Time Factors; Valproic Acid

Case series suggest that some antipsychotics may induce or exacerbate type 2 diabetes. This study measured the association of antipsychotic treatments with diabetes at a population level.. Claims data for psychosis patients (ICD-CM-9 290.xx-299.xx) within health plans encompassing 2.5 million individuals were analyzed. Patients reporting preexisting type 2 diabetes up to 8 months prior to observation were excluded. The frequency of newly reported type 2 diabetes in untreated patients and among patients treated with antipsychotics from 5 categories (risperidone, olanzapine, clozapine, and high-potency and low-potency conventionals) was compared. Logistic regression models compared the odds of diabetes based on exposure to each of the antipsychotic categories.. Based on 12 months of exposure, the odds of type 2 diabetes for risperidone-treated patients (odds ratio = 0.88, 95% CI = 0.372 to 2.070) was not significantly different from that for untreated patients, whereas patients receiving other antipsychotics had a significantly greater risk of diabetes than untreated patients (p < .05): olanzapine, 3.10 (95% CI = 1.620 to 5.934); clozapine, 7.44 (95% CI = 0.603 to 34.751); high-potency conventionals, 2.13 (95% CI = 1.097 to 4.134); and low-potency conventionals, 3.46 (95% CI = 1.522 to 7.785). Older age and greater use of non-antipsychotic psychotropic medications also contributed to risk of type 2 diabetes. Olanzapine also showed significantly higher (p < .01) odds of diabetes associated with increasing dose.. Consistent with previously published literature, these data suggest that olanzapine, clozapine, and some conventional antipsychotics appear to increase the risk of acquiring or exacerbating type 2 diabetes and that the effect may vary by drug. In contrast to these agents, risperidone was not associated with an increased risk of type 2 diabetes.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Comorbidity; Confidence Intervals; Databases as Topic; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Insurance Claim Review; Logistic Models; Male; Middle Aged; Odds Ratio; Olanzapine; Pirenzepine; Psychotic Disorders; Risk Factors; Risperidone; United States

Topics: Acute Disease; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Double-Blind Method; Humans; Olanzapine; Pirenzepine; Placebo Effect; Psychotherapy

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Humans; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic; Treatment Outcome

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Eosinophilia; Humans; Male; Olanzapine; Pirenzepine; Psychotic Disorders; Selective Serotonin Reuptake Inhibitors

Topics: Acute Disease; Age Factors; Antipsychotic Agents; Benzodiazepines; Child; Dose-Response Relationship, Drug; Female; Humans; Olanzapine; Pirenzepine; Psychomotor Agitation

Acute, high-dose loading strategies (rapid neuroleptization) with the first-generation antipsychotics administered orally or parenterally, alone or combined with benzodiazepines, have been a commonly used treatment paradigm for controlling acutely agitated psychotic patients. The rationale was to achieve high plasma levels of drug within a shorter time period, resulting in rapid symptom mitigation. However, studies have shown that rapid neuroleptization with first-generation antipsychotics is associated with a greater incidence of side effects. To our knowledge, loading strategies with second-generation antipsychotics have not been investigated, primarily owing to a need for dose titration. Olanzapine, a second-generation antipsychotic, is well tolerated in doses ranging from 5 to 20 mg. The objective of this report was to determine experience with the use of up to 20 mg of an oral loading dose of olanzapine administered within 4 hours in the treatment of patients early in an acute psychotic phase of their illness. In the reported case series of 57 patients, olanzapine initiated at 15 to 20 mg/day was a safe and effective medication for rapidly calming the agitation of acutely agitated psychotic patients (rapid tranquilization). Furthermore, dose reduction over 2 to 3 weeks was achieved in a number of patients without appreciable loss of efficacy.

Topics: Acute Disease; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Drug Administration Schedule; Humans; Incidence; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Psychotic Disorders

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Administration Schedule; Drug Approval; Humans; Olanzapine; Pirenzepine; Psychotic Disorders; Schizophrenia; United States; United States Food and Drug Administration

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Drug Therapy, Combination; Emergency Service, Hospital; Female; Haloperidol; Humans; Neuroleptic Malignant Syndrome; Olanzapine; Pirenzepine; Schizophrenia

Topics: Acute Disease; Adult; Benzodiazepines; Clonazepam; Drug Therapy, Combination; Female; Humans; Injections, Intramuscular; Olanzapine; Pirenzepine; Schizophrenia, Catatonic

Typical antipsychotics are commonly used in combination with mood stabilizers for acute mania. Although typical antipsychotics are effective, they have undesirable side effects such as induction of depressive symptoms and tardive dyskinesia. Atypical antipsychotics have more favorable side effect profiles, and recent evidence shows their efficacy in treating mania. Apart from a previous small study that compared risperidone with typical neuroleptics as add-on therapy to mood stabilizers, no studies to date have directly compared atypical antipsychotics with typical antipsychotics as add-on therapy to mood stabilizers in a clinically relevant, naturalistic setting.. This study is a chart review of all patients with DSM-IV-defined bipolar disorder, current episode mania (N = 204), admitted to the University of British Columbia Hospital during a 30-month period. Patients were separated into 3 groups according to the medications used: (1) mood stabilizer and typical antipsychotic, (2) mood stabilizer and atypical antipsychotic, and (3) combination: mood stabilizer plus a typical antipsychotic, then switched to mood stabilizer plus risperidone or olanzapine within I week. The atypical group was further subdivided into risperidone and olanzapine subgroups. Outcome was measured using Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) ratings generated by review of clinical information in the chart.. Patients treated with typical antipsychotics were more severely ill at admission and at discharge than those treated with atypical antipsychotics. Patients in the atypical (p < .005) and combination (p < .05) groups showed significantly greater clinical improvement at discharge than patients treated with typical antipsychotics. This difference was also significant in the subset of patients with psychotic features (p < .03). Risperidone and olanzapine were associated with fewer extrapyramidal side effects than were typical antipsychotics (risperidone vs. typical antipsychotics, chi2 = 8.72, p < .01; olanzapine vs. typical antipsychotics, chi2 = 16.9, p < .001).. Due to their superior effectiveness and side effect profile when compared with typical antipsychotics. atypical antipsychotics are an excellent choice as add-on therapy to mood stabilizers for the treatment of patients with mania.

Topics: Acute Disease; Adult; Antimanic Agents; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Bipolar Disorder; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Length of Stay; Male; Middle Aged; Neurologic Examination; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Retrospective Studies; Risperidone; Treatment Outcome

Topics: Acute Disease; Amisulpride; Antipsychotic Agents; Benzodiazepines; Clozapine; Cost-Benefit Analysis; Dibenzothiazepines; Dibenzothiepins; Dyskinesia, Drug-Induced; Germany; Humans; Neurotransmitter Agents; Olanzapine; Patient Compliance; Pirenzepine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Sulpiride

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Female; Humans; Hypericum; Male; Olanzapine; Pirenzepine; Plants, Medicinal; Recurrence; Risperidone; Schizophrenia

To report the first published case of olanzapine-induced acute pancreatitis.. A 72-year-old white woman was admitted to the intensive care unit (ICU) with acute hemorrhagic pancreatitis and unintentional verapamil overdose. The patient did not consume alcohol and had undergone a cholecystectomy in the past; other medical causes of pancreatitis had been ruled out. She was taking several medications chronically, but olanzapine was started six days prior to the onset of acute abdominal symptoms. According to the Naranjo probability scale, olanzapine was considered the probable cause of acute pancreatitis in this patient. Following a 12-day stay in the ICU, the patient was transferred to the ward where she died a few days later of unrelenting peritonitis secondary to acute pancreatitis.. A literature search (1966-July 2000) and contact with the manufacturer failed to detect any published reports of acute pancreatitis associated with olanzapine. The contribution of concomitant medications taken prior to ICU admission in initiating or worsening the pancreatitis was deemed unlikely. More common causes of acute pancreatitis, such as ethanol consumption and gallstones, were also ruled out in this patient. Therefore, olanzapine was rated as a probable cause for acute pancreatitis in our patient. The mechanism of this adverse reaction is unknown.. This is believed to be the first published report suspecting olanzapine, an atypical antipsychotic agent, to have caused acute hemorrhagic pancreatitis in a patient, leading to admission to the ICU and, eventually, death secondary to unrelenting peritonitis.

Topics: Acute Disease; Aged; Antipsychotic Agents; Benzodiazepines; Fatal Outcome; Female; Hemorrhage; Humans; Olanzapine; Pancreatitis; Pirenzepine

Topics: Acute Disease; Affect; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Bipolar Disorder; Drug Monitoring; Dyskinesia, Drug-Induced; Humans; Olanzapine; Pirenzepine

Clozapine may be effective in adults and adolescents with treatment-resistant bipolar disorder. Olanzapine has a receptor affinity profile similar to that of clozapine.. The responses of seven consecutive adolescents (ages 12-17) with DSM-IV bipolar disorder, manic episode, treated with olanzapine were evaluated. Response to olanzapine was rated as marked, moderate, minimal, none or worse.. Five (71%) adolescents showed a marked or moderate response. The mean+/-SD olanzapine dose was 0.146+/-0.086 mg/kg/day (11+/-6 mg/day).. Olanzapine may have antimanic effects in some adolescents with acute mania. Controlled studies of olanzapine in adolescent bipolar disorder appear to be warranted.

Topics: Acute Disease; Adolescent; Benzodiazepines; Bipolar Disorder; Child; Female; Humans; Male; Olanzapine; Pirenzepine; Psychology, Adolescent; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Dystonia; Female; Humans; Olanzapine; Pirenzepine

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Comorbidity; Humans; Male; Obsessive-Compulsive Disorder; Olanzapine; Pirenzepine; Schizophrenia

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Dystonia; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Schizophrenia, Paranoid

Topics: Acute Disease; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Child; Drug Overdose; Humans; Male; Olanzapine; Pirenzepine; Suicide, Attempted