olanzapine and Psychomotor-Agitation

To provide updated guidance for the medication treatment of acute agitation in the setting of psychosis or mania on inpatient psychiatric units.. This topic presented challenges: studies are sparse, tend to be under-powered, and are difficult to compare. Though there have been few recent studies, there have been several recent meta-analyses, Cochrane reviews, and published guidelines that sift through the primarily older evidence as well as more recent trials. The reviewers often do not agree on what seems to have the best evidence for efficacy and safety.. We conclude that the best approach is to summarize in some detail the evidence for each possible treatment and the interpretations published recently on each of those treatments, and then present recommendations for medication management in tiered rankings, based on the authors' qualitative review of the data and opinions. For oral treatment, the first-tier options are (alphabetically) haloperidol with lorazepam, lorazepam alone, and olanzapine. The second tier includes haloperidol with promethazine, loxapine inhaler, and risperidone alone. Tier 3 includes asenapine and quetiapine. For intramuscular treatment, the first-tier includes haloperidol plus promethazine, and olanzapine alone, and the second-tier includes haloperidol with lorazepam, and lorazepam alone.

Topics: Antipsychotic Agents; Benzodiazepines; Drug Therapy, Combination; Haloperidol; Humans; Lorazepam; Mania; Olanzapine; Promethazine; Psychomotor Agitation; Psychopharmacology; Psychotic Disorders

Psychomotor agitation is a common condition in patients with psychotic disorders. One treatment possibility is intramuscular (IM) second-generation antipsychotics. Yet their efficacy in this formulation and for this aim is unclear. This network meta-analysis aims to evaluate the efficacy of short-acting IM second-generation antipsychotic drugs, haloperidol and placebo in patients with diagnosis of schizophrenia and schizophrenia-like disorders that present acute agitation.. We searched the Cochrane Schizophrenia Group Controlled Trials Register, MEDLINE, EMBASE, PsycINFO, Cochrane Library, PubMed, BIOSIS, ClinicalTrials.gov and WHO ICTRP up to November 2018 and PubMed until March 2020. Study selection and outcome extraction were performed independently by two reviewers. Pairwise and network meta-analyses were conducted to compare the different IM second-generation antipsychotics among themselves and with IM haloperidol and placebo. The primary outcome was the number of responders at 2 h after the first injection. Responders at 24 h were also analysed.. 10 studies with 1964 patients were included in the meta-analysis. Ziprasidone, olanzapine, aripiprazole and haloperidol were more efficacious than placebo in calming patients at 2 h after administration. Furthermore, olanzapine was superior to aripiprazole. The results at 24 h confirmed the superiority of aripiprazole, olanzapine and haloperidol over placebo, while for ziprasidone no data were available.. All second-generation antipsychotics available as intramuscular medications were effective in reducing agitation in people with schizophrenia. Olanzapine was somewhat more efficacious than aripiprazole.

Topics: Antipsychotic Agents; Benzodiazepines; Haloperidol; Humans; Injections, Intramuscular; Network Meta-Analysis; Olanzapine; Psychomotor Agitation; Schizophrenia

Topics: Aggression; Antipsychotic Agents; Bipolar Disorder; Dexmedetomidine; Drug Development; Drugs, Investigational; Humans; Olanzapine; Psychomotor Agitation; Schizophrenia

Non-pharmacological interventions preferably precede pharmacological interventions in acute agitation. Reviews of pharmacological interventions remain descriptive or compare only one compound with several other compounds. The goal of this study is to compute a systematic review and meta-analysis of the effect on restoring calmness after a pharmacological intervention, so a more precise recommendation is possible.. A search in Pubmed and Embase was done to isolate RCT's considering pharmacological interventions in acute agitation. The outcome is reaching calmness within maximum of 2 h, assessed by the psychometric scales of PANSS-EC, CGI or ACES. Also the percentages of adverse effects was assessed.. Fifty-three papers were included for a systematic review and meta-analysis. Most frequent studied drug is olanzapine. Changes on PANNS-EC and ACES at 2 h showed the strongest changes for haloperidol plus promethazine, risperidon, olanzapine, droperidol and aripiprazole. However, incomplete data showed that the effect of risperidon is overestimated. Adverse effects are most prominent for haloperidol and haloperidol plus lorazepam.. Olanzapine, haloperidol plus promethazine or droperidol are most effective and safe for use as rapid tranquilisation. Midazolam sedates most quickly. But due to increased saturation problems, midazolam is restricted to use within an emergency department of a general hospital.

Topics: Aggression; Anti-Anxiety Agents; Antipsychotic Agents; Benzodiazepines; Drug Therapy, Combination; Haloperidol; Humans; Hypnotics and Sedatives; Lorazepam; Midazolam; Olanzapine; Promethazine; Psychomotor Agitation; Psychotic Disorders; Treatment Outcome

People experiencing psychosis may become aggressive. Antipsychotics, such as aripiprazole in intramuscular form, can be used in such situations.. To evaluate the effects of intramuscular aripiprazole in the treatment of psychosis-induced aggression or agitation (rapid tranquillisation).. On 11 December 2014 and 11 April 2017, we searched the Cochrane Schizophrenia Group's Study-based Register of Trials which is based on regular searches of CINAHL, BIOSIS, AMED, Embase, PubMed, MEDLINE, PsycINFO, and registries of clinical trials.. All randomised controlled trials (RCTs) that randomised people with psychosis-induced aggression or agitation to receive either intramuscular aripiprazole or another intramuscular intervention.. We independently inspected citations and, where possible, abstracts, ordered papers and re-inspected and quality assessed these. We included studies that met our selection criteria. At least two review authors independently extracted data from the included studies. We chose a fixed-effect model. We analysed dichotomous data using risk ratio (RR) and the 95% confidence intervals (CI). We analysed continuous data using mean differences (MD) and their CIs. We assessed risk of bias for included studies and used GRADE to create 'Summary of findings' tables.. Searching found 63 records referring to 21 possible trials. We could only include three studies, all completed over the last decade, with 885 participants, of which 707 were included for quantitative analyses in this systematic review. Due to limited comparisons, small size of trials and a paucity of investigated and reported 'pragmatic' outcomes, evidence was mostly graded as low or very low quality. No trials reported useful data for one of our primary outcomes of tranquil or asleep by 30 minutes. Economic outcomes were also not reported in the trials.When compared with placebo, fewer people in the aripiprazole group needed additional injections compared to the placebo group (2 RCTs, n = 382, RR 0.69, 95% CI 0.56 to 0.85, very low-quality evidence). Clinically important improvement in agitation at two hours favoured the aripiprazole group (2 RCTs, n = 382, RR 1.50, 95% CI 1.17 to 1.92, very low-quality evidence). The numbers of non-responders after the first injection also favoured aripiprazole (1 RCT, n = 263, RR 0.49, 95% CI 0.34 to 0.71, low-quality evidence). Although no effect was found, more people in the aripiprazole compared to the placebo group experienced adverse effects (1 RCT, n = 117, RR 1.51, 95% CI 0.93 to 2.46, very low-quality evidence).Aripiprazole required more injections compared to haloperidol (2 RCTs, n = 477, RR 1.28, 95% CI 1.00 to 1.63, very low-quality evidence), with no significant difference in agitation (2 RCTs, n = 477, RR 0.94, 95% CI 0.80 to 1.11, very low-quality evidence), and similar non-responders after first injection (1 RCT, n = 360, RR 1.18, 95% CI 0.78 to 1.79, low-quality evidence). Aripiprazole and haloperidol did not differ when taking into account the overall number of people that experienced at least one adverse effect (1 RCT, n = 113, RR 0.91, 95% CI 0.61 to 1.35, very low-quality evidence).Compared to aripiprazole, olanzapine was better at reducing agitation (1 RCT, n = 80, RR 0.77, 95% CI 0.60 to 0.99, low-quality evidence) and had a more favourable effect on global state change scores (1 RCT, n = 80, MD 0.58, 95% CI 0.01 to 1.15, low-quality evidence), both at two hours. No differences were found in terms of experiencing at least one adverse effect during the 24 hours after treatment (1 RCT, n = 80, RR 0.75, 95% CI 0.45 to 1.24, very low-quality evidence). However, participants allocated to aripiprazole experienced less somnolence (1 RCT, n = 80, RR 0.25, 95% CI 0.08 to 0.82, low-quality evidence).. The available evidence is of poor quality but there is some evidence aripiprazole is effective compared to placebo and haloperidol, but not when compared to olanzapine. However, considering that evidence comes from only three studies, caution is required in generalising these results to real-world practice. This review firmly highlights the need for more high-quality trials on intramuscular aripiprazole in the management of people with acute aggression or agitation.

Topics: Aggression; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Haloperidol; Humans; Injections, Intramuscular; Olanzapine; Psychomotor Agitation; Randomized Controlled Trials as Topic; Tranquilizing Agents

The main goal of antipsychotic medication in the management of acute agitation in the emergency department is to rapidly induce calm without oversedation, enabling patients to participate in their own care. However, there is a paucity of comparative studies, particularly with newer fast-acting second-generation antipsychotic agents.. This structured evidence-based review compared the onset of efficacy of antipsychotic treatments for acute agitation using data from randomized controlled trials identified by a literature search of the PubMed database.. Based on findings from 28 blinded randomized controlled trials, onset of efficacy was rapid and generally observed at the first time point after intramuscular administration of ziprasidone (15-30 min) or olanzapine (15-30 min), but was more likely to be delayed with intramuscular haloperidol, even when combined with lorazepam (30-60 min), and intramuscular aripiprazole (45-90 min). When administered orally, rapid onset of efficacy was also consistently observed at the first assessment time point with olanzapine (15-120 min), risperidone (30-120 min), and sublingual asenapine (15 min). Significant effects were apparent for inhaled loxapine within 10-20 min. Effects were apparent within approximately 5-10 min with i.v. droperidol. Onset of efficacy was typically more rapid with second-generation antipsychotic agents than benzodiazepines, but data are limited.. Although the patient populations of trials included in this review do not truly reflect that of the emergency department, the results provide useful information to emergency physicians on the rapid efficacy of certain newer-generation antipsychotic agents for the treatment of acutely agitated patients.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Drug Therapy; Evidence-Based Practice; Haloperidol; Humans; Injections, Intramuscular; Olanzapine; Psychomotor Agitation

Psychomotor agitation is associated with different psychiatric conditions and represents an important issue in psychiatry. Current recommendations on agitation in psychiatry are not univocal. Actually, an improper assessment and management may result in unnecessary coercive or sedative treatments. A thorough and balanced review plus an expert consensus can guide assessment and treatment decisions.. An expert task force iteratively developed consensus using the Delphi method. Initial survey items were based on systematic review of the literature. Subsequent surveys included new, re-worded or re-rated items.. Out of 2175 papers assessing psychomotor agitation, 124 were included in the review. Each component was assigned a level of evidence. Integrating the evidence and the experience of the task force members, a consensus was reached on 22 statements on this topic.. Recommendations on the assessment of agitation emphasise the importance of identifying any possible medical cause. For its management, experts agreed in considering verbal de-escalation and environmental modification techniques as first choice, considering physical restraint as a last resort strategy. Regarding pharmacological treatment, the "ideal" medication should calm without over-sedate. Generally, oral or inhaled formulations should be preferred over i.m. routes in mildly agitated patients. Intravenous treatments should be avoided.

Topics: Antipsychotic Agents; Benzodiazepines; Consensus; Disease Management; Emergency Medical Services; Humans; Meta-Analysis as Topic; Olanzapine; Practice Guidelines as Topic; Psychiatric Status Rating Scales; Psychiatry; Psychomotor Agitation; Randomized Controlled Trials as Topic; Risk Factors

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

We performed an updated systematic review and meta-analysis of randomized controlled trials (RCTs) of intramuscular (IM)-olanzapine (OLA-IM) versus controls in agitated patients. The risk ratio, number-needed-to-treat/harm, and standardized mean difference based on a random effects model were calculated. We identified 13 RCTs (19 comparisons) as follows: 7 comparisons with 1059 patients for OLA-IM versus placebo; 5 comparisons with 613 patients for OLA-IM versus haloperidol (HAL)-IM; 2 comparisons with 108 patients for OLA-IM versus ziprasidone (ZIP)-IM; 2 comparisons with 110 patients for OLA-IM versus HAL-IM plus midazolam; and 3 comparisons with 412 patients for OLA-IM versus HAL-IM plus promethazine, 2 comparisons with 355 patients for OLA-IM versus lorazepam-IM (LOR-IM); and 1 comparison with 67 patients for OLA-IM versus HAL-IM plus LOR-IM. OLA-IM was superior to placebo in both Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) and Agitation-Calmness Evaluation Scale (ACES) scores 2 h after first injection, and had a comparable side effect profile, including over sedation, extrapyramidal symptoms, akathisia, and anticholinergic use. While there was no significant difference in PANSS-EC scores after 2 h between OLA-IM and HAL-IM, OLA-IM outperformed HAL-IM in ACES after 2 h. Compared with HAL-IM, OLA-IM was associated with fewer side effects, including anticholinergic use, akathisia, extrapyramidal symptoms, and dystonia, and marginally less QT prolongation compared with HAL-IM. Based on our findings, OLA-IM is preferable to HAL-IM for the treatment of agitated patients. However, comparator data for ZIP-IM, LOR-IM and HAL-IM combination therapy were insufficient.

Topics: Antipsychotic Agents; Benzodiazepines; Haloperidol; Humans; Olanzapine; Psychomotor Agitation; Randomized Controlled Trials as Topic

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

The objective of this article is to assess the clinical characteristics of akathisia in patients with schizophrenia, schizoaffective disorder, or bipolar I disorder receiving aripiprazole, haloperidol, olanzapine, or placebo. We conducted post hoc analyses of pooled safety data from trials in patients with schizophrenia, schizoaffective disorder, and bipolar I disorder. Outcome measures included the incidence of akathisia, time to onset, duration, severity, and discontinuation due to akathisia, concomitant use of benzodiazepines and/or anticholinergics, Barnes Akathisia Rating Scale (BARS) scores, and the correlation between antipsychotic efficacy and akathisia. The results for schizophrenia and schizoaffective disorder were as follows: akathisia in 9% of aripiprazole- and 6% of placebo-treated patients; 12.5% of aripiprazole- versus 24% of haloperidol-treated patients; 11% of aripiprazole- versus 6% of olanzapine-treated patients. Bipolar I disorder: akathisia in 18% of aripiprazole- and 5% of placebo-treated patients. The clinical characteristics of akathisia were similar between each data set, regardless of disease. Akathisia was generally mild-to-moderate in severity. Discontinuation due to akathisia was low in both the schizophrenia trials (aripiprazole 0.3%; placebo 0%; aripiprazole 0.9%; haloperidol 2.3%; aripiprazole 1.2%; olanzapine 0.2%) and the bipolar trials (aripiprazole 2.3%; placebo 0%). Treatment-emergent akathisia was not associated with a poorer clinical response. In conclusion, akathisia with aripiprazole occurred early in treatment, was mild-to-moderate in severity, led to few study discontinuations, and did not compromise therapeutic efficacy.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Haloperidol; Humans; Hypnotics and Sedatives; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychomotor Agitation; Psychotic Disorders; Quinolones; Randomized Controlled Trials as Topic; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Akathisa is one of the most common and distressing neuroleptic-induced extrapyramidal side effects. Although it is well recognized in the context of conventional antipsychotic medications, there have been recent concerns raised by clinicians and researchers that this syndrome is overlooked in relation to second-generation or atypical antipsychotics. This review examines the recent literature relevant to second-generation antipsychotic (SGA)-induced akathisia.. Recent studies using large databases clearly indicate that extrapyramidal side effects, in particular akathisia, do occur with the SGAs, although the frequency is not as high as with the conventional antipsychotics. Risk factors include use of high doses, high potency SGAs, or combinations of SGAs with other psychotropic drugs, bipolar depression, palliative care settings, and comorbid substance abuse in psychosis. The dopamine hypothesis remains plausible for understanding the pathophysiology of akathisia. There is emerging evidence that mirtazapine may be useful in the treatment of acute akathisia.. Even though akathisia is less prevalent with SGAs than with the first-generation drugs, it remains clinically important and all clinicians should be conversant with its recognition and management.

Topics: Amisulpride; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Dibenzothiazepines; Humans; Isoxazoles; Olanzapine; Piperazines; Piperidines; Prevalence; Psychomotor Agitation; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risk Factors; Risperidone; Sulpiride; Thiazoles

Health services often manage agitated or violent people, and for emergency psychiatric services such behaviour is particularly prevalent (10%). The drugs used in this situation should ensure that the person swiftly and safely regains composure.. To examine whether haloperidol plus promethazine is an effective treatment for psychosis induced agitation/aggression.. We searched the Cochrane Schizophrenia Group's Register (January 2008).. We included all randomised clinical trials involving aggressive people with psychosis for which haloperidol plus promethazine was being used.. We reliably selected, quality assessed and extracted data from all relevant studies. For binary outcomes we calculated standard estimations of risk ratio (RR) and their 95% confidence intervals (CI). Where possible we estimated weighted number needed to treat or harm (NNT/H).. We identified four relevant high quality studies. One compared the haloperidol plus promethazine mix with midazolam (n=301), one with lorazepam (n=200), one with haloperidol alone (n=316) and one with olanzapine IM (n=300). In Brazil, haloperidol plus promethazine was an effective means of tranquillisation with over two thirds of people being tranquil or sedated by 30 minutes, but midazolam was more swift (n=301, RR 2.9 CI 1.75 to 4.80, NNH 5 CI 3 to 12). In India, compared with lorazepam, more people were tranquil or sedated by 30 minutes if allocated to the combination treatment (n=200, RR 0.26 CI 0.10 to 0.68, NNT 8 CI 6 to 17). Over the next few hours of treatment reported differences are negligible. One person given midazolam had respiratory depression (0.7%, reversed by flumazenil); one given lorazepam (1%) had respiratory difficulty. About 1% of people given any haloperidol treatment experienced a seizure. By 20 minutes intramuscular haloperidol plus promethazine was more tranquillising than intramuscular haloperidol (1 RCT, n=316, RR 0.65 CI 0.49 to 0.87, NNT 7 CI 5 to 17). Haloperidol given without promethazine in this situation causes frequent serious adverse effects (NNH 15 CI 14 to 40). Olanzapine is as rapidly tranquillising as the haloperidol/promethazine combination (1 RCT, n=300, RR tranquil or asleep at 15 mins 0.74 CI 0.38 to 1.41), but did not have an enduring effect and more people needed additional drugs within four hours (1 RCT, n=300, RR 0.48 CI 0.33 to 0.69, NNT 5 CI 4 to 8) and to be re-assessed by the doctor (1 RCT, n=300, RR 0.47 CI 0.30 to 0.73, NNT 6 CI 5 to 12).. All treatments evaluated within the included studies are effective. Benzodiazepines, however, have the potential to cause respiratory depression, probably midazolam more so than lorazepam, and use of this group of drugs outside of services fully confident of observing for and managing the consequences of respiratory distress is difficult to justify. Haloperidol used on its own is at such risk of generating preventable adverse effects that unless it is the only choice, this evidence directs that this sole treatment should be avoided. Olanzapine IM is valuable when compared with haloperidol plus promethazine but its duration of action is short and re-injection is frequently needed. Haloperidol plus promethazine used in two diverse situations in Brazil and India has much evidence to support its swift and safe clinically valuable effects.

Topics: Aggression; Benzodiazepines; Drug Therapy, Combination; Haloperidol; Humans; Lorazepam; Midazolam; Olanzapine; Promethazine; Psychomotor Agitation; Psychotic Disorders; Randomized Controlled Trials as Topic

Rapid and safe tranquillisation is sometimes unavoidable. We conducted this systematic review to determine the value of the combination haloperidol plus promethazine, frequently used in Brazil.. We searched the Cochrane Schizophrenia Group's Register and included all randomised clinical trials involving aggressive people with psychosis for which haloperidol plus promethazine was being used. We reliably selected, quality assessed and extracted data from all relevant studies.. We identified four relevant high quality studies. The combination haloperidol plus promethazine mix was compared with midazolam, lorazepam, haloperidol alone and olanzapine Intramuscular. In Brazil, haloperidol plus promethazine was effective with over 2/3 of people being tranquil by 30 minutes, but midazolam was more swift and in India, compared with lorazepam, the combination was more effective. Over the next few hours reported differences are negligible. Haloperidol given without promethazine in this situation causes frequent serious adverse effects. Olanzapine is as rapidly tranquillising as haloperidol plus promethazine, but did not have an enduring effect and more people needed additional drugs within 4 hours.. All treatments evaluated are effective, but this review provides compelling evidence as to clear advantages of the haloperidol plus promethazine combination.

Topics: Anti-Anxiety Agents; Antipsychotic Agents; Benzodiazepines; Drug Therapy, Combination; Haloperidol; Humans; Lorazepam; Midazolam; Olanzapine; Promethazine; Psychomotor Agitation; Randomized Controlled Trials as Topic

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

Agitation can present as an emergency in the course of numerous psychiatric conditions including intoxication, schizophrenia, bipolar disorder, and delirium. This article reviews relevant literature regarding the definition, etiology, measurement, and management of episodic agitation and pays particular attention to intramuscular treatments. The impact of changes in methodology between the era of first- and second-generation antipsychotics, the implications of those changes for external validity of studies of second-generation studies, and the recent evolution of expert consensus are discussed.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Dibenzothiazepines; Emergencies; Humans; Olanzapine; Piperazines; Psychomotor Agitation; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Thiazoles

To compare the efficacy and safety of the intramuscular formulations of ziprasidone, olanzapine, and aripiprazole in treating agitation.. The pivotal registration trials were accessed by querying on-line literature and clinical trial databases. Pharmacovigilance data and posters were requested from the manufacturers. No date or language constraints were applied.. Nine double-blind, randomized, controlled clinical trials were identified.. Number needed to treat (NNT) for response to treatment for agitation and number needed to harm (NNH) for extrapyramidal effects were calculated from the study reports. Additional safety outcomes subject to NNH analysis were obtained from product labeling.. Using the a priori definitions of response at 2 hours after the first injection, NNT for response versus placebo (or placebo equivalent) in treating agitation for the pooled data at the recommended dose of ziprasidone 10-20 mg was 3 (95% CI = 2 to 4), for olanzapine 10 mg was 3 (95% CI = 2 to 3), and for aripiprazole 9.75 mg was 5 (95% CI = 4 to 8). Treatment-emergent adverse events occurring during the pivotal trials revealed statistically significant NNH versus placebo (or placebo equivalent) for aripiprazole for headache (NNH = 20, 95% CI = 11 to 170) and nausea (NNH = 17, 95% CI = 11 to 38), for ziprasidone in the treatment of headache (NNH = 15, 95% CI = 8 to 703), and for olanzapine in treatment-emergent hypotension (NNH = 50, 95% CI = 30 to 154). Olanzapine and aripiprazole had a more favorable extrapyramidal side effect profile compared to haloperidol. (There was no haloperidol treatment arm in the ziprasidone studies.). Although the lowest NNT, and hence strongest therapeutic effect, was seen for the studies of ziprasidone and olanzapine as opposed to aripiprazole, head-to-head controlled studies directly comparing these 3 agents are needed.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Double-Blind Method; Humans; Injections, Intramuscular; Olanzapine; Piperazines; Psychomotor Agitation; Quinolones; Randomized Controlled Trials as Topic; Schizophrenia; Thiazoles; Treatment Outcome

Aggression, agitation or psychosis occur in the majority of people with dementia at some point in the illness. There have been a number of trials of atypical antipsychotics to treat these symptoms over the last five years, and a systematic review is needed to evaluate the evidence in a balanced way.. To determine whether evidence supports the use of atypical antipsychotics for the treatment of aggression, agitation and psychosis in people with Alzheimer's disease.. The trials were identified from a last updated search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 7 December 2004 using the terms olanzapine, quetiapine, risperidone, clozapine, amisulpride, sertindole, zotepine, aripiprazole, ziprasidone. This Register contains articles from all major healthcare databases and many ongoing trials databases and is updated regularly.. Randomised, placebo-controlled trials, with concealed allocation, where dementia and psychosis and/or aggression were assessed.. 1. Two reviewers extracted data from included trials2. Data were pooled where possible, and analysed using appropriate statistical methods3. Analysis included patients treated with an atypical antipsychotic, compared with placebo. Sixteen placebo controlled trials have been completed with atypical antipsychotics although only nine had sufficient data to contribute to a meta-analysis and only five have been published in full in peer reviewed journals. No trials of amisulpiride, sertindole or zotepine were identified which met the criteria for inclusion. The included trials led to the following results:1. There was a significant improvement in aggression with risperidone and olanzapine treatment compared to placebo.2. There was a significant improvement in psychosis amongst risperidone treated patients.3. Risperidone and olanzpaine treated patients had a significantly higher incidence of serious adverse cerebrovascular events (including stroke), extra-pyramidal side effects and other important adverse outcomes.4. There was a significant increase in drop-outs in risperidone (2 mg) and olanzapine (5-10 mg) treated patients.5. The data were insufficient to examine impact upon cognitive function.. Evidence suggests that risperidone and olanzapine are useful in reducing aggression and risperidone reduces psychosis, but both are associated with serious adverse cerebrovascular events and extra-pyramidal symptoms. Despite the modest efficacy, the significant increase in adverse events confirms that neither risperidone nor olanzapine should be used routinely to treat dementia patients with aggression or psychosis unless there is marked risk or severe distress. Although insufficient data were available from the considered trials, a meta-analysis of seventeen placebo controlled trials of atypical neuroleptics for the treatment of behavioural symptoms in people with dementia conducted by the Food and Drug Administration (using data not in the public domain) suggested a significant increase in mortality (OR 1.7).

Topics: Aggression; Alzheimer Disease; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Dibenzothiazepines; Humans; Mental Disorders; Olanzapine; Piperazines; Psychomotor Agitation; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risperidone

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

To review the current efficacy and safety evidence for the use of intramuscular olanzapine in the management of acute agitation.. MEDLINE, EMBASE, and PubMed (all to March 2004) were searched for full-text, English-language publications in humans. Search terms included olanzapine, psychosis, agitation, psychiatric emergency, and intramuscular.. Prospective, randomized, controlled trials that evaluated efficacy or safety endpoints of intramuscular olanzapine in the management of acute agitation were included. All studies were evaluated independently by both authors. For clinical outcomes (efficacy, safety), the definitions as specified by each study were used.. Four prospective trials were included in this review. Intramuscular olanzapine is comparable to haloperidol or lorazepam monotherapy in managing acute agitation associated with schizophrenia and dementia. Intramuscular olanzapine is superior to lorazepam monotherapy in the management of agitation associated with bipolar affective disorder. Preliminary evidence demonstrates that intramuscular olanzapine is associated with fewer adverse movement disorders than monotherapy with intramuscular haloperidol. Interpretation of published evidence is limited by confounding factors of comparator regimens and the patient populations studied.. Additional studies comparing intramuscular olanzapine with combination antipsychotic/benzodiazepine therapy in more severely ill patients and patients with concomitant medical illnesses are needed to determine the most effective dosing regimen, use of adjunctive medications, and to obtain a comprehensive safety profile.

Topics: Antipsychotic Agents; Benzodiazepines; Humans; Injections, Intramuscular; Olanzapine; Psychomotor Agitation; Randomized Controlled Trials as Topic; Treatment Outcome

The safety and efficacy of i.m. ziprasidone and olanzapine for treating acute agitation in patients with schizophrenia are described, along with factors to consider when evaluating the cost-effectiveness of these agents. Agitation is defined as excessive motor and verbal activity. Acute agitation has traditionally been treated with the combination of haloperidol 5 mg and lorazepam 2 mg i.m. Controlled trials have shown, however, that combination therapy of haloperidol or droperidol plus lorazepam i.m. is better than single-drug treatment at one hour but not earlier. Phase II and III clinical trials showed that both i.m. ziprasidone mesylate 10 mg and 20 mg and olanzapine 2.5 mg-10 mg controlled agitation faster in patients with schizophrenia than p.o. ziprasidone 2 mg and placebo. In addition, i.m. olanzapine 10 mg controlled agitation faster in patients with schizophrenia faster than haloperidol in 15 minutes. Olanzapine i.m. was also superior to placebo in patients with dementia and in patients with bipolar disorder with and without psychotic symptoms, suggesting that agitation may be a syndrome that is similar across a multitude of disease states. Dystonic reactions occurred in 2.6% of patients taking ziprasidone, compared with 9.2% of patients taking haloperidol. No patients receiving olanzapine experienced a dystonic reaction. Ziprasidone has been associated with prolonged QTc Intervals. Pharmaco-economic evaluations should include costs associated with repeat i.m. injections for agitated patients, increased time in the emergency room, case of switching from i.m. to oral therapy, adverse effects, and relapse, as well as medication costs. I.m. olanzapine and ziprasidone show promise for treating acute agitation in patients with schizophrenia, especially because of their safer adverse effect profile and faster onset of effectiveness compared with haloperidol.

Topics: Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Continuity of Patient Care; Cost-Benefit Analysis; Drug Therapy, Combination; Economics, Pharmaceutical; Humans; Olanzapine; Piperazines; Pirenzepine; Psychomotor Agitation; Schizophrenia; Thiazoles; Treatment Outcome

Topics: Anti-Dyskinesia Agents; Antipsychotic Agents; Benzodiazepines; Haloperidol; Humans; Injections, Intramuscular; Olanzapine; Piperazines; Pirenzepine; Psychomotor Agitation; Psychotic Disorders; Thiazoles

Akathisia (restlessness and characteristic movements of the legs) is one of the most disagreeable extrapyramidal side effects and often causes non-compliance. Dopamine blocking agents such as antipsychotics and antiemetics, may induce akathisia. Particular care must be taken to distinguish akathisia from psychotic agitation and restless legs. The prevalence of akathisia in patients using classical antipsychotics is 20-30% and for users of clozapine, olanzapine and quetiapine (atypical antipsychotics) it is lower. Risk factors are a high dosage of antipsychotics, akathisia in a previous treatment, and diabetes mellitus. The treatment of akathisia starts, if possible, with the antipsychotic being withdrawn or the dose administered being lowered. Another treatment possibility is switching to clozapine, olanzapine or quetiapine, or adding a beta-blocking agent, an anticholinergic or mianserin.

Topics: Akathisia, Drug-Induced; Antipsychotic Agents; Benzodiazepines; Clozapine; Diabetes Complications; Diagnosis, Differential; Dibenzothiazepines; Dose-Response Relationship, Drug; Humans; Olanzapine; Pirenzepine; Prevalence; Psychomotor Agitation; Quetiapine Fumarate; Recurrence; Restless Legs Syndrome; Risk Factors

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

The management of agitation and aggression in psychiatric inpatients is a significant clinical dilemma. Establishing a clear diagnosis and distinguishing whether aggression is an acute manifestation or a long-standing or repetitive problem are fundamental antecedents of medication treatment. For acute aggression, either benzodiazepines or antipsychotic medications (typical and atypical) are recommended choices. Currently, on the basis of efficacy, ease of use, and availability in multiple (tablet, liquid, intramuscular) preparations, typical antipsychotics such as loxapine should be considered as first choice for acute aggression (in psychosis). On the other hand, atypical antipsychotics, particularly clozapine, should be considered when aggression in psychosis persists and/or is repetitive. Typical antipsychotics are indicated for persistent aggression in psychosis when medication noncompliance is the obstacle to effective treatment.

Topics: Aggression; Antipsychotic Agents; Benzodiazepines; Clozapine; Humans; Loxapine; Mental Disorders; Olanzapine; Pirenzepine; Psychomotor Agitation; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology

A multicenter randomized clinical trial in Hong Kong Accident and Emergency (A&E) departments concluded that intramuscular (IM) olanzapine is noninferior to haloperidol and midazolam, in terms of efficacy and safety, for the management of acutely agitated patients in A&E setting. Determining their comparative cost-effectiveness will further provide an economic perspective to inform the choice of sedative in this setting.. This analysis used data from a randomized clinical trial conducted in Hong Kong A&E departments between December 2014 and September 2019. A within-trial cost-effectiveness analysis comparing the 3 sedatives was conducted, from the A&E perspective and a within-trial time horizon, using a decision-analytic model. Sensitivity analyses were also undertaken.. In the base-case analysis, median total management costs associated with IM midazolam, haloperidol, and olanzapine were Hong Kong dollar (HKD) 1958.9 (US dollar [USD] 251.1), HKD 2504.5 (USD 321.1), and HKD 2467.6 (USD 316.4), respectively. Agitation management labor cost was the main cost driver, whereas drug costs contributed the least. Midazolam dominated over haloperidol and olanzapine. Probabilistic sensitivity analyses supported that midazolam remains dominant > 95% of the time and revealed no clear difference in the cost-effectiveness of IM olanzapine versus haloperidol (incremental cost-effectiveness ratio 667.16; 95% confidence interval -770.89, 685.90).. IM midazolam is the dominant cost-effective treatment for the management of acute agitation in the A&E setting. IM olanzapine could be considered as an alternative to IM haloperidol given that there is no clear difference in cost-effectiveness, and their adverse effect profile should be considered when choosing between them.

Topics: Antipsychotic Agents; Benzodiazepines; Cost-Benefit Analysis; Emergency Service, Hospital; Haloperidol; Humans; Injections, Intramuscular; Midazolam; Olanzapine; Psychomotor Agitation

The phenomenon of restlessness, agitation, or cognitive disturbances experienced by dying patients is well-known in palliative care; more than half of these patients will experience delirium symptoms at end-of-life. When not identified early and effectively managed, delirium symptoms could lead to caregiver and patient distress and harm.. Eighty patients with a prognosis of 7 days or less will be recruited for an open-label randomised control trial. The two arms compare oral-transmucosal haloperidol 2.5 mg vs olanzapine 5 mg over 72 h. The severity of agitation, delirium and toxicities of treatments will be compared at the 24th, 48th and 72nd hour after drug administration.. This trial is the first to compare anti-psychotics in the management of delirium at the dying stage in the home hospice setting using the oral transmucosal route. Ethical considerations, as well as recruitment procedures, are discussed.. This study was registered in ClinicalTrials.gov - identifier NCT04750395.

Topics: Antipsychotic Agents; Delirium; Haloperidol; Humans; Olanzapine; Psychomotor Agitation

Agitation is common in the early stages of recovery from traumatic brain injury (TBI), when patients are in post-traumatic amnesia (PTA). Agitation is associated with risk of harm to patients and caregivers. Recent guidelines recommend that agitation during PTA is managed using environmental modifications. Agitation is also frequently treated pharmacologically, with the use of atypical antipsychotics such as olanzapine among the most common. This is despite a lack of well-designed studies to support the use of antipsychotics within this context. This study will be a double-blind, placebo-controlled randomised controlled trial. We will examine the efficacy, safety, cost-effectiveness and outcomes associated with the use of olanzapine for reducing agitation in patients in PTA following TBI over and above recommended environmental management.. Fifty-eight TBI rehabilitation inpatients who are in PTA and are agitated will receive olanzapine or placebo for the duration of PTA. All participants will additionally receive optimal environmental management for agitation. Measures of agitation, PTA and health will be undertaken at baseline. Treatment administration will begin at a dose of 5 mg daily and may be escalated to a maximum dose of 20 mg per day. Throughout the treatment period, agitation and PTA will be measured daily, and adverse events monitored weekly. Efficacy will be assessed by treatment group comparison of average Agitated Behaviour Scale scores during PTA. Participants will cease treatment upon emergence from PTA. Agitation levels will continue to be monitored for a further 2 weeks, post-treatment measures of health will be undertaken and cognitive and functional status will be assessed. Level of agitation and functional health will be assessed at hospital discharge. At 3 months post-discharge, functional outcomes and health service utilisation will be measured.. This trial will provide crucial evidence to inform the management of agitation in patients in PTA following TBI. It will provide guidance as to whether olanzapine reduces agitation over and above recommended environmental management or conversely whether it increases or prolongs agitation and PTA, increases length of inpatient hospitalisation and impacts longer term cognitive and functional outcomes. It will also speak to the safety and cost-effectiveness of olanzapine use in this population.. ANZCTR ACTRN12619000284167 . Registered on 25 February 2019.

Topics: Antipsychotic Agents; Brain Injuries, Traumatic; Humans; Olanzapine; Patient Discharge; Psychomotor Agitation; Randomized Controlled Trials as Topic; Reproducibility of Results

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 evaluate and compare the effectiveness and adverse effects of intramuscular (IM) olanzapine and IM aripiprazole for the treatment of agitated patients with schizophrenia in clinical practice.. A 24-hour randomized double-blind study carried out at a psychiatric hospital in Thailand enrolled adult patients (18-65years old) with schizophrenia experiencing agitation. Patients received one dose of IM olanzapine or IM aripiprazole followed by routine oral psychotropic medications. Efficacy was primarily measured using the Excited Component of the Positive and Negative Syndrome Scale (PANSS-EC).. A total of 80 patients with a PANSS-EC score range of 22-35 entered the study, of whom 13% had a medical comorbidity and 40% a history of active substance abuse. The 40 patients receiving IM olanzapine showed greater improvement than the 40 patients receiving IM aripiprazole in PANSS-EC scores at 2h after the injection (p=0.002) but not at 24h. The two treatments were well tolerated. Patients receiving IM olanzapine experienced greater somnolence than those receiving IM aripiprazole. There were no clinically relevant changes in vital signs in either group.. The results indicate that IM olanzapine and aripiprazole are similarly effective and well tolerated in the real-world treatment of agitation associated with schizophrenia over the first 24h. However, in the early hours, IM olanzapine may produce more sedation and reductions in agitation.

Topics: Adolescent; Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Comparative Effectiveness Research; Double-Blind Method; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Psychomotor Agitation; Schizophrenia; Treatment Outcome; Young Adult

To compare the efficacy and safety profile between intramuscular (IM) olanzapine and IM haloperidol plus IM lorazepam in acute schizophrenic patients with moderate to severe agitation.. This was a prospective, randomized, open-label study. Acutely agitated patients with schizophrenia or schizoaffective disorder (n = 67) were randomized to receive 10 mg IM olanzapine (n = 37) or 5 mg IM haloperidol plus 2 mg IM lorazepam (n = 30). Agitation was measured with Positive and Negative Syndrome Scale Excited Component (PANSS-EC) and Agitation-Calmness Evaluation Scale (ACES) during the first 2 hours and at 24 hours after the first injection. Safety was assessed using the Simpson-Angus Scale and Barnes Akathisia Rating Scale and by recording adverse events at 24 hours following the first injection. The Clinical Global Impression-Severity scale was also rated.. The PANSS-EC scores decreased significantly at 2 hours after the first injection in both groups (olanzapine: -10.2, p < 0.001; haloperidol + lorazepam: -9.9, p < 0.001). Haloperidol plus lorazepam was not inferior to olanzapine in reducing agitation at 2 hours. There were no significant differences in PANSS-EC or ACES scores between the two groups within 2 hours following the first injection. The frequencies of adverse events and changes in Clinical Global Impression-Severity, Simpson-Angus Scale, and Barnes Akathisia Rating Scale scores from baseline to 24 hours showed no significant differences between the groups.. The findings suggest that IM haloperidol (5 mg) plus lorazepam (2 mg) is not inferior to IM olanzapine (10 mg) in the treatment of acute schizophrenic patients with moderate to severe agitation (ClinialTrials.gov identifier number NCT00797277).

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Drug Therapy, Combination; Female; Haloperidol; Humans; Injections, Intramuscular; Lorazepam; Male; Middle Aged; Olanzapine; Prospective Studies; Psychiatric Status Rating Scales; Psychomotor Agitation; Psychotic Disorders; Schizophrenia; Taiwan; Treatment Outcome

Agitation is a major problem in acute schizophrenia. Only a few studies have tested antipsychotic agents in severely agitated patients, mainly because of legal issues. Furthermore, most studies were limited to the first 24 hours. We aimed to investigate the efficacy of oral haloperidol, risperidone, and olanzapine in reducing psychotic agitation in severely agitated patients with schizophrenia or schizophreniform or schizoaffective disorder over 96 hours using a prospective, randomized, rater-blinded, controlled design within a naturalistic treatment regimen.. In total, 43 severely agitated patients at acute care psychiatric units were enrolled. Participants were randomly assigned to receive either daily haloperidol 15 mg, olanzapine 20 mg, or risperidone 2 to 6 mg over 5 days. Positive and Negative Syndrome Scale psychotic agitation subscale score was the primary outcome variable. A mixed-model analysis was applied.. All drugs were effective for rapid tranquilization within 2 hours. Over 5 days, the course differed between agents (P < 0.001), but none was superior. Dropouts occurred only in the risperidone and olanzapine groups. Men responded better to treatment than did women during the initial 2 hours (P = 0.046) as well as over the 5-day course (P < 0.001). No difference between drug groups was observed regarding diazepam or biperiden use.. Oral haloperidol, risperidone, and olanzapine seem to be suitable for treating acute severe psychotic agitation in schizophrenia spectrum disorders. Response to oral antipsychotics demonstrated a gender effect with poorer outcome in women throughout the study.

Topics: Administration, Oral; Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Female; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Prospective Studies; Psychiatric Status Rating Scales; Psychomotor Agitation; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Sex Factors; Switzerland; Time Factors; Treatment Outcome; Young Adult

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

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

Olanzapine rapid-acting intramuscular (IM) injection is an atypical antipsychotic drug already used overseas and recently approved in Japan. The objective of this study was to confirm the efficacy of rapid-acting IM olanzapine 10 mg was greater than IM placebo in patients with exacerbation of schizophrenia with acute psychotic agitation by comparing changes from baseline to 2 hours after the first IM injection, as measured by the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) total score.. We conducted a placebo-controlled, randomized, double-blind, parallel-group study in Japanese patients diagnosed with schizophrenia according to the diagnostic criteria specified in the DSM-IV-TR. Patients were randomized to 2 treatment groups: IM olanzapine (10 mg) or IM placebo. The primary efficacy outcome was the change in PANSS-EC from baseline to 2 hours after the first IM injection. Treatment groups were compared with an analysis of variance model which included treatment and site as factors. During the 24-hour treatment period, safety was assessed by clinical examination and laboratory investigations, electrocardiograms, extrapyramidal symptoms scales, and recording spontaneously reported adverse events.. Of the 91 randomized patients, 90 patients (45 IM olanzapine-group; 45 IM placebo-group) were in the full analysis set. The mean change of PANSS-EC total score from baseline to 2 hours after the first IM injection (mean±standard deviation) was -9.2±4.5 for the IM olanzapine group and -2.8±5.6 for the IM placebo group. The difference between treatment groups was statistically significant (p<.001). There were no deaths, serious adverse events, treatment-emergent adverse events (TEAEs) leading to discontinuation, severe TEAEs, or instances of oversedation in this study. There were no statistically significant differences between treatment groups in the proportion of patients with potentially clinically significant changes in laboratory tests, vital signs (blood pressure and pulse rate), electrocardiograms, and treatment-emergent extrapyramidal symptoms.. The efficacy of IM olanzapine 10 mg in patients with exacerbation of schizophrenia with acute psychotic agitation was greater than IM placebo in the primary efficacy measure, PANSS-EC. Intramuscular olanzapine 10 mg was shown to be generally safe and tolerable, and could be a new option for treatment of schizophrenia in Japan.. NCT00970281.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Female; Humans; Injections, Intramuscular; Japan; Male; Middle Aged; Olanzapine; Psychomotor Agitation; Schizophrenia; Treatment Outcome; Young Adult

To compare the effectiveness of intramuscular olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol alone as the first medication(s) used to treat patients with agitation and aggressive behavior.. One hundred fifty patients with agitation caused by psychotic or bipolar disorder were randomly assigned under double-blind conditions to receive olanzapine, ziprasidone, haloperidol plus midazolam, haloperidol plus promethazine or haloperidol alone. The Overt Agitation Severity Scale, Overt Aggression Scale and Ramsay Sedation Scale were applied within 12 hours after the first dosage.. All medications produced a calming effect within one hour of administration, but only olanzapine and haloperidol reduced agitation by less than 10 points, and only olanzapine reduced aggression by less than four points in the first hour. After twelve hours, only patients treated with haloperidol plus midazolam had high levels of agitation and aggression and also more side effects. Ziprasidone, olanzapine and haloperidol alone had more stable results for agitation control, while ziprasidone, haloperidol plus promethazine and olanzapine had stable results for aggression control.. Olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol were effective in controlling agitation and aggression caused by mental illness over 12 hours. Although all the drugs had advantages and disadvantages, haloperidol plus midazolam was associated with the worst results in all the observed parameters.

Topics: Adult; Aggression; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Drug Therapy, Combination; Emergency Services, Psychiatric; Female; Haloperidol; Humans; Hypnotics and Sedatives; Injections, Intramuscular; Male; Midazolam; Olanzapine; Piperazines; Promethazine; Psychomotor Agitation; Psychotic Disorders; Thiazoles; Tranquilizing Agents

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

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

The study measured the effects of atypical antipsychotics on psychiatric and behavioral symptoms in patients with Alzheimer's disease and psychosis or agitated behavior.. The Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) Alzheimer's disease effectiveness study included 421 outpatients with Alzheimer's disease and psychosis or agitated/aggressive behavior. Patients were assigned randomly to masked, flexible-dose treatment with olanzapine, quetiapine, risperidone, or placebo for up to 36 weeks. Patients could be randomly reassigned to a different medication at the clinician's discretion, which ended phase 1. Psychiatric and behavioral symptoms, functioning, cognition, care needs, and quality of life were measured at regular intervals.. In relation to placebo, the last observation in phase 1 showed greater improvement with olanzapine or risperidone on the Neuropsychiatric Inventory total score, risperidone on the Clinical Global Impression of Changes, olanzapine and risperidone on the Brief Psychiatric Rating Scale (BPRS) hostile suspiciousness factor, and risperidone on the BPRS psychosis factor. There was worsening with olanzapine on the BPRS withdrawn depression factor. Among patients continuing phase 1 treatment at 12 weeks, there were no significant differences between antipsychotics and placebo on cognition, functioning, care needs, or quality of life, except for worsened functioning with olanzapine compared to placebo.. In this descriptive analysis of outpatients with Alzheimer's disease in usual care settings, some clinical symptoms improved with atypical antipsychotics. Antipsychotics may be more effective for particular symptoms, such as anger, aggression, and paranoid ideas. They do not appear to improve functioning, care needs, or quality of life.

Topics: Activities of Daily Living; Aged; Aggression; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Brief Psychiatric Rating Scale; Cognition Disorders; Dibenzothiazepines; Female; Humans; Male; Neuropsychological Tests; Olanzapine; Psychomotor Agitation; Psychotic Disorders; Quality of Life; Quetiapine Fumarate; Risperidone; Surveys and Questionnaires

Agitation is a common phenomenon in schizophrenia or acute mania. Because of the inability of patients to give informed consent in such situations, data from consenting studies are limited.. This observational prospective 5-day study evaluated the effectiveness of olanzapine in a sample of highly agitated patients with aggression. Primary endpoint was mean change of the PANSS-Excited Component (PANSS-EC) score.. Mean PANSS-EC score at baseline was 25.5 points, 60.2% were severely agitated and 41.6% severely aggressive. A significant decrease in PANSS-EC total score (-13.3 points) was observed with rapid dose escalation and an average daily dose of 21.2 mg/day of olanzapine. 40 patients (24.1%) required treatment with another antipsychotic and 21 patients (12.7%) were not treated with olanzapine at day 5. At endpoint, 64.2% of patients were in remission of agitation. PANSS-EC reduction was not significantly different in patients with or without concurrent benzodiazepine use.. Severe agitation with aggression may be well controlled with olanzapine in many cases, possibly by higher initial and overall doses of olanzapine. Controlled studies are needed to confirm these findings.

Topics: Adult; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Male; Middle Aged; Olanzapine; Prospective Studies; Psychomotor Agitation; Psychotic Disorders; Schizophrenia; Severity of Illness Index; Time Factors; Treatment Outcome

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

Acute agitation is a common presentation in emergency departments and is often secondary to an underlying psychotic condition. The aim of this study was to compare the effectiveness of three second generation antipsychotics (risperidone, olanzapine, quetiapine) versus haloperidol in the treatment of psychotic agitation for up to 72 h.. We recruited 101 patients with acute psychosis who were admitted at the Mental Health Department 1 South of Turin, Psychiatric Emergency Service of San Giovanni Battista Hospital, from June 2004 to June 2005.. Aggressive behavior, as measured by Modified Overt Aggression Scale and Hostility-suspiciousness factor derived from the Brief Psychiatric Rating Scale, significantly improved in all groups, with no significant between-group differences. Extrapyramidal symptoms were more common in haloperidol treated patients compared with patients receiving risperidone, olanzapine or quetiapine.. Our results show that in the clinical practice setting of emergency psychiatry olanzapine, risperidone, quetiapine are as effective as haloperidol and better tolerated.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aggression; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Brief Psychiatric Rating Scale; Dibenzothiazepines; Emergency Services, Psychiatric; Female; Haloperidol; Hostility; Humans; Italy; Male; Middle Aged; Olanzapine; Prospective Studies; Psychomotor Agitation; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

To determine the effect of intramuscular (IM) olanzapine in severely agitated patients.. This was an open-label multicenter 1-week observational study of IM olanzapine treatment in severely agitated inpatients and psychiatric emergency services with bipolar mania (n = 22) or schizophrenia (n = 52). Mean change from baseline to 2 h post-first injection (LOCF) in agitation was assessed by PANSS-Excited Component (PANSS-EC) (score range: 5-35 points) mean change from baseline to 15, 30, 45, 60, 90, and 120 min post-first injection, and visit-wise mean changes from mixed-model repeated measures analysis of variance. Kaplan-Meier survival curve analyses estimated time to categorical response (rating of

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Injections, Intramuscular; Kaplan-Meier Estimate; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Psychomotor Agitation; Schizophrenia; Schizophrenic Psychology

To compare the effect of intramuscular olanzapine with intramuscular haloperidol plus promethazine on rapid tranquillisation of agitated or violent people with mental illness.. Pragmatic, allocation concealed, randomised controlled trial.. Emergency services of a general hospital psychiatry department in Vellore, south India.. 300 adults with agitated or violent behaviour as a result of mental illness; 150 randomised to intramuscular olanzapine and 150 randomised to intramuscular haloperidol plus promethazine.. Open treatment with intramuscular olanzapine or intramuscular haloperidol plus promethazine.. Primary outcome was proportion of patients who were tranquil or asleep at 15 minutes and 240 minutes. Secondary outcomes were proportion of patients who were tranquil, asleep, restrained, absconding, or clinically improved at 15, 30, 60, 120, and 240 minutes; additional medical interventions and adverse effects over four hours; and compliance with oral drugs and adverse effects over two weeks.. Of 300 people randomised to receive either intramuscular olanzapine or intramuscular haloperidol plus promethazine, follow-up data were available for primary outcomes for 298 (99%). Both treatments resulted in similar proportions of people being tranquil or asleep at 15 minutes (olanzapine 131/150 (87%), haloperidol plus promethazine 136/150 (91%); relative risk 0.96, 95% confidence interval 0.34 to 1.47) and 240 minutes (olanzapine 144/150 (96%), haloperidol plus promethazine 145/150 (97%); relative risk 0.99, 0.95 to 1.03). However, more people given olanzapine than those given haloperidol plus promethazine required additional drugs over four hours (65/150 (43%) v 31/150 (21%); relative risk 2.07, 1.43 to 2.97). Adverse effects were uncommon with both treatments.. Intramuscular olanzapine and intramuscular haloperidol plus promethazine were effective at rapidly tranquillising or sedating agitated or violent patients with mental illness but the combination resulted in fewer additional medical interventions within four hours of intervention.. Clinical trials NCT00455234 [ClinicalTrials.gov].

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Drug Combinations; Emergency Services, Psychiatric; Haloperidol; Humans; India; Injections, Intramuscular; Mental Disorders; Olanzapine; Promethazine; Psychomotor Agitation; Treatment Outcome; Violence

The goal of this study was to compare the efficacy and safety of olanzapine versus haloperidol in the treatment of agitation and aggression in patients with dementia. The subjects were 58 out-patients with dementia and agitation. After baseline assessments and, if necessary, a period of wash-out of a previous antipsychotic drug, they were randomly assigned to 5 weeks of double-blind treatment with either olanzapine or haloperidol. The first 2 weeks were used for dose titration. Subsequently, the patients received a fixed dose of either olanzapine (average dose 4.71 mg) or haloperidol (average dose 1.75 mg) from day 14 to day 35. Both olanzapine and haloperidol decreased agitation significantly (decrease in Cohen-Mansfield Agitation Inventory scores), but there was no significant difference between the two drugs. The two drugs had comparable effects on all secondary outcome measures. They were well tolerated and had a similar side-effect pattern. Our study could not demonstrate the superiority of olanzapine, compared to haloperidol, for the treatment of agitation in patients with dementia.

Topics: Aged; Aggression; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Haloperidol; Humans; Olanzapine; Psychomotor Agitation

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

The authors compared efficacy of olanzapine versus placebo and risperidone as measured by the Neuropsychiatric Inventory and Clinical Global Impression-Severity of Psychosis scale in patients with dementia-related psychosis.. Patients with moderate-to-severe psychotic symptoms associated with dementia were recruited from outpatient or residential settings and randomly assigned to 10-week, double-blind, flexible-dose treatment with olanzapine (N=204; 2.5 mg-10 mg/day; mean: 5.2 mg/day), risperidone (N=196; 0.5 mg-2 mg/day; mean: 1.0 mg/day) or placebo (N=94).. Most measures of neuropsychiatric functioning improved in all treatment groups, including the placebo group, and no significant treatment differences occurred. Overall discontinuation was lowest in the placebo group, and the olanzapine group had a significantly higher incidence of discontinuation due to adverse events (16.2%) relative to placebo (3.2%) and risperidone (8.7%) groups. Treatment-emergent extrapyramidal symptoms were more numerous for risperidone- than placebo- or olanzapine-treated patients. Abnormally high prolactin levels occurred in 78.0% of risperidone patients, compared with 16.7% for olanzapine and 5.0% for placebo. The incidence of weight gain greater than 7% from baseline was higher in the olanzapine group relative to risperidone, but neither active-treatment group showed a statistical difference from placebo (1.1%). No other statistically significant and clinically relevant differences were seen for any other vital sign, electrocardiographic measure, or laboratory hematology and chemistry, including glucose, except for cholesterol, which decreased from baseline to endpoint in both active-treatment groups.. Patients' neuropsychiatric functioning improved with olanzapine, risperidone, and placebo treatment. There was a substantial response in the placebo group, and no significant differences emerged among treatments.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Brief Psychiatric Rating Scale; Comorbidity; Conduct Disorder; Dementia, Vascular; Depressive Disorder, Major; Double-Blind Method; Female; Humans; Male; Neuropsychological Tests; Olanzapine; Psychomotor Agitation; Risperidone; Treatment Outcome

This was an exploratory study of olanzapine as potential treatment for improvement in cognition in patients with Alzheimer's disease without prominent psychobehavioral symptoms.. Non-psychotic/non-agitated patients (n = 268) with Alzheimer's disease, who had baseline Mini-Mental State Examination (MMSE) scores of 14-26 were randomized to treatment with olanzapine (2.5 to 7.5 mg/d) or placebo for 26 weeks. The primary objectives were to determine if treatment with olanzapine improved cognition as indexed by the Alzheimer's disease Assessment Scale for Cognition (ADAS-Cog) and the Clinician's Interview-Based Impression of Change (CIBIC) after 26 weeks of therapy.. Patients treated with olanzapine vs placebo experienced significant worsening ADAS-Cog scores at weeks 12 (p = 0.03) and 26 (p = 0.004). Changes in CIBIC scores were not significantly different between treatment groups at either assessment. A post hoc analysis revealed that olanzapine-treated patients with more cognitive impairment at baseline (MMSE scores of 14-18) (n = 35) experienced significantly greater deterioration in ADAS-Cog performance than patients in the placebo group (n = 24; p < 0.001); whereas in patients with less cognitive impairment (n = 78, baseline MMSE scores of 23-26) between-group ADAS-Cog changes were not significant.. In this 26-week study non-psychotic/non-agitated patients with Alzheimer's disease treated with olanzapine experienced significant worsening of cognition as compared to placebo.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Disease Progression; Double-Blind Method; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Olanzapine; Prospective Studies; Psychiatric Status Rating Scales; Psychomotor Agitation; Treatment Outcome

Topics: Administration, Oral; Antipsychotic Agents; Benzodiazepines; Diagnostic and Statistical Manual of Mental Disorders; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Injections, Intramuscular; Male; Olanzapine; Psychomotor Agitation; Schizophrenia

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

Distinct calming rather than nonspecific sedation is desirable for the treatment of acute agitation. In 3 double-blind studies, acutely agitated patients with schizophrenia (N = 311), bipolar mania (N = 201), or dementia (N = 206) were treated with intramuscular (1-3 injections/24 hrs) olanzapine (2.5-10.0 mg), haloperidol (7.5 mg), lorazepam (2.0 mg), or placebo. The Agitation-Calmness Evaluation Scale (ACES; Eli Lilly and Co.) and treatment-emergent adverse events assessed sedation. Across all studies, 1 patient (lorazepam-treated, bipolar) became unarousable. There were no significant between-group differences in ACES scores of deep sleep or unarousable at any time across. Excluding asleep patients, agitation remained significantly more reduced with olanzapine than placebo (P <.05). The incidences of adverse events indicative of sedation were not significantly different with olanzapine versus comparators. For the treatment of acute agitation associated with schizophrenia, bipolar mania, or dementia, intramuscular olanzapine-treated patients experienced no more sedation than haloperidol- or lorazepam-treated patients and experienced distinct calming rather than nonspecific sedation.

Topics: Adult; Anti-Anxiety Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dementia; Double-Blind Method; Drug Administration Schedule; Haloperidol; Humans; Hypnotics and Sedatives; Injections, Intramuscular; Lorazepam; Olanzapine; Pirenzepine; Psychomotor Agitation; Retrospective Studies; Schizophrenia; Treatment Outcome

Prolongation of the QTc interval has been reported during treatment with oral antipsychotic agents and may be more pronounced during parenteral administration. Pooled QTc interval data from acutely agitated patients across four double-blind trials were compared. Databases included: placebo-controlled [two schizophrenia, one bipolar mania trials (n=565)]; haloperidol-controlled [two schizophrenia trials (n=482)]; geriatric placebo-controlled [1 dementia trial (n=204)]. Patients received 1-3 injections of intramuscular (IM) olanzapine (2.5-10 mg/injection), IM haloperidol (7.5 mg/injection), or IM placebo. At 2 and 24 h after IM olanzapine treatment, the mean QTc interval decreased approximately 3 ms from baseline in the placebo- and haloperidol-controlled databases. When there was a statistically significant difference between IM olanzapine and IM placebo, QTc intervals decreased during treatment with IM olanzapine and increased with IM placebo. The incidences of prolonged (endpoint >/=99th percentile of healthy adults or >/=500 ms) or lengthened (increase >/=60 ms) QTc intervals during treatment with IM olanzapine (<3% placebo- and haloperidol-controlled databases, <12% geriatric placebo-controlled database) were never significantly greater than with comparators. These data suggest that IM olanzapine has a favorable QTc interval profile in acutely agitated patients with schizophrenia, bipolar mania, or dementia.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dementia; Dose-Response Relationship, Drug; Double-Blind Method; Electrocardiography; Haloperidol; Humans; Injections, Intramuscular; Long QT Syndrome; Olanzapine; Psychomotor Agitation; Schizophrenia

Patients experiencing an acute decompensation of schizophrenia or bipolar disorder often present in an agitated state. Agitation presents a barrier to therapy, interrupting the typical physician-patient alliance and creating a disruptive, even hazardous, environment. Rapid assessment and effective treatment are necessary to manage agitation and, potentially, to shorten the time to recovery.. One hundred forty-eight acutely agitated patients received either: rapid initial dose escalation (RIDE) in which up to 40 mg of oral olanzapine was allowed on days 1 and 2, up to 30 mg on days 3 and 4, and 5 to 20 mg thereafter; or usual clinical practice (UCP) in which patients received 10 mg/d olanzapine plus up to 4 mg lorazepam on days 1 and 2, up to 2 mg on days 3 and 4, and olanzapine 5 to 20 mg/d thereafter. The Positive and Negative Syndrome Scale-Excited Component (PANSS-EC: poor impulse control, tension, hostility, uncooperativeness, and excitement) measured at 24 hours was the primary measure. Secondary assessments of agitation and safety were also performed.. Agitation improved significantly from baseline for both treatment groups; however, improvement with the RIDE strategy was superior to UCP. The RIDE group improvement was superior on the primary efficacy measure (PANSS-Excited) at 24 hours; it was superior on all agitation measures at the end of double-blind treatment. Both treatments were well tolerated, with no clinically significant differences in safety measures. Treatment was not limited by oversedation and attention improved from baseline in both groups.. This study demonstrates the value of olanzapine in the treatment of acutely agitated patients. A new approach to olanzapine dosing that expands the initial dose range up to 40 mg/d may offer superior efficacy in rapidly and effectively controlling the symptoms of agitation.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Psychomotor Agitation

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

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

Elderly patients with Alzheimer's disease (AD) commonly exhibit psychotic symptoms, prompting clinicians to administer antipsychotics. This article compares the effects of olanzapine and placebo in the emergence of hallucinations or delusions in AD patients with symptoms of agitation/aggression but little or no psychotic symptomatology at baseline.. A multicenter, double-blind, placebo-controlled study was conducted in nursing home patients with AD according to DSM-IV criteria and symptoms of agitation/aggression and/or psychosis. Patients (N = 206) were randomly assigned to receive either placebo or fixed-dose olanzapine (5, 10, or 15 mg/day) for up to 6 weeks. This article analyzes data from a subgroup of patients (N = 165) with no or minimal delusions and/or hallucinations at baseline as measured by the Neuropsychiatric Inventory-Nursing Home Version (NPI/NH). Three subsets of patients were identified on the basis of their symptoms at baseline: those with no clinically significant hallucinations, those with no clinically significant delusions, and those with no clinically significant delusions or hallucinations.. Of the patients without hallucinations or delusions at baseline (N = 75), the placebo-treated patients showed significantly greater development of these symptoms compared with olanzapine-treated patients overall (NPI/NH hallucinations + delusions mean change score, +2.73 vs. +0.27, p = .006). Similarly, of the patients without baseline hallucinations (N = 153), the placebo-treated patients showed greater hallucinations score increases than did olanzapine-treated patients overall (+1.25 vs. +0.33, p = .026), whereas patients without baseline delusions (N = 87) showed no significant treatment effects. Olanzapine had a favorable safety profile in each patient subset.. These results suggest that, overall, olanzapine effectively attenuated emergence of psychosis in a short-term trial of patients with Alzheimer's disease.

Topics: Aged; Aged, 80 and over; Aggression; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Delusions; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Hallucinations; Humans; Male; Nursing Homes; Olanzapine; Pirenzepine; Psychomotor Agitation; Psychotic Disorders; Treatment Outcome

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

This first clinical study of olanzapine in Japanese patients with schizophrenia was conducted to investigate the efficacy and safety of olanzapine. Eighty-one patients were included in the analysis set. Mean modal dose for those patients were 9.4 +/- 3.6 mg/day. For the primary efficacy measure (Final Global Improvement Rating score), 14.8% of patients had remarkable improvement, 59.3% of patients had moderate improvement or better, and 86.4% of patients had slight improvement or better. Results from the Brief Psychiatric Rating Scale showed improvement from baseline in all clusters including positive psychotic symptoms (thought disturbance) but also against negative symptoms (anergia). The most commonly reported treatment-emergent signs and symptoms with > or =10% incidence, were insomnia, weight increase, excitement, sleepiness, and anxiety. There was a low incidence of extrapyramidal treatment-emergent signs and symptoms, and events reported were tremor (6.2%), muscle rigidity (3.7%), and akathisia (2.5%). The most commonly reported treatment-emergent laboratory changes, with > or = 20% of incidence, were prolactin elevations (24.3%) followed by increases in triglycerides (20.4%). However, mean prolactin values tended to be normalized during the study. This study result suggests that olanzapine is an "atypical" antipsychotic.

Topics: Adult; Akathisia, Drug-Induced; Antipsychotic Agents; Anxiety; Benzodiazepines; Female; Humans; Japan; Male; Muscle Rigidity; Olanzapine; Pirenzepine; Prolactin; Psychiatric Status Rating Scales; Psychomotor Agitation; Schizophrenia; Sleep Wake Disorders; Treatment Outcome; Tremor; Triglycerides; Weight Gain

There are no rapid-acting intramuscular formulations of atypical antipsychotics available for quickly calming an agitated patient with bipolar disorder. In this study, 201 agitated patients with bipolar mania were randomly assigned to receive one to three injections of the atypical antipsychotic olanzapine (10 mg, first two injections; 5 mg, third injection), the benzodiazepine lorazepam (2 mg, first two injections; 1 mg, third injection), or placebo (placebo, first two injections; olanzapine, 10 mg, third injection) within a 24-hour period. Agitation was measured at baseline, every 30 minutes for the first 2 hours, and at 24 hours after the first injection using the Positive and Negative Syndrome Scale-Excited Component subscale and two additional agitation scales. At 2 hours after the first injection, patients treated with olanzapine showed a significantly greater reduction in scores on all agitation scales compared with patients treated with either placebo or lorazepam. At 24 hours after the first injection, olanzapine remained statistically superior to placebo in reducing agitation in patients with acute mania, whereas patients treated with lorazepam were not significantly different from those treated with placebo or olanzapine. Furthermore, no significant differences among the three treatment groups were observed in safety measures, including treatment-emergent extrapyramidal symptoms, the incidence of acute dystonia, or QTc interval changes. These findings suggest that intramuscular olanzapine is a safe and effective treatment for reducing acute agitation in patients with bipolar mania.

Topics: Adult; Affect; Anti-Anxiety Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cholinergic Antagonists; Double-Blind Method; Female; Heart Rate; Humans; Injections, Intramuscular; Lorazepam; Male; Middle Aged; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Psychomotor Agitation; Treatment Outcome

The authors describe the development of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) protocol for Alzheimer disease (AD), a trial developed in collaboration with the National Institute of Mental Health (NIMH), assessing the effectiveness of atypical antipsychotics for psychosis and agitation occurring in AD outpatients. They provide an overview of the methodology utilized in the trial as well as the clinical-outcomes and effectiveness measures that were implemented.

Topics: Aged; Algorithms; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Citalopram; Cost-Benefit Analysis; Humans; Olanzapine; Patient Compliance; Pirenzepine; Psychomotor Agitation; Psychotic Disorders; Risperidone; Treatment Outcome

To compare the efficacy and frequency of akathisia and dystonia between the dopamine antagonist headache medications olanzapine, metoclopramide and prochlorperazine.. This was a retrospective observational cohort study of patients presenting to a large urban level one trauma center between 2010 and 2018. Inclusion criteria was age ≥ 18 who presented to the emergency department with a chief complaint of headache who received either olanzapine, metoclopramide or prochlorperazine. The primary outcome was need for rescue medication. Secondary outcomes were receiving medication for either akathisia or dystonia. Logistic regression was used to identify differences between the three cohorts up to 72 h from initial presentation.. There were 5643 patients who met inclusion criteria. Olanzapine was the most commonly used drug (n = 2994, 53%) followed by prochlorperazine (n = 2100, 37%) and metoclopramide (n = 549, 10%). After adjusting for age and gender, there were no differences in risk for receiving rescue therapy or developing akathisia or dystonia.. During initial ED visit and up to 72 h after receiving olanzapine, metoclopramide or prochlorperazine, we found no difference in risk for requiring rescue medication or developing akathisia or dystonia.

Topics: Cohort Studies; Double-Blind Method; Dystonia; Emergency Service, Hospital; Headache; Humans; Metoclopramide; Migraine Disorders; Olanzapine; Prochlorperazine; Psychomotor Agitation

Many psychotic patients are treated with antipsychotic medications during acute agitation and aggressive behavior episodes in an attempt to achieve a rapid calming effect. Those medications include olanzapine, zuclopenthixol acetate, and haloperidol intramuscular administration. This study compared the effectiveness of these injections in reducing the need for restraint during agitated-psychotic episodes that include aggression. Sociodemographical and clinical data were retrieved from the electronic medical records of 179 patients who needed rapid calming while hospitalized in a mental health center with acute psychosis. The treatments administered were olanzapine intramuscular, zuclopenthixol acetate intramuscular, and haloperidol intramuscular. The assessed outcomes were rate of restraint and violent behavior. Olanzapine was found significantly more effective in reducing the need for restraint compared to zuclopenthixol acetate. No significant differences were found between haloperidol and the other two with regard to restraint. Neither were other significant differences found between the groups with regard to violent or self-harming behaviors. No significant differences were found in the rate of violent behavior and antipsychotic dosage at discharge. In conclusion, in inpatients with acute agitated psychosis, olanzapine intramuscular shows better efficacy in reducing the need for restraint, at least as compared to zuclopenthixol acetate intramuscular.

Topics: Antipsychotic Agents; Benzodiazepines; Clopenthixol; Haloperidol; Humans; Injections, Intramuscular; Olanzapine; Psychomotor Agitation; Psychotic Disorders

Antipsychotics with dopamine (D2) receptor antagonism can be effective for emesis in cancer patients. Extrapyramidal symptoms (EPS) induced by typical antipsychotics can be exacerbated by other D2 receptor antagonists. We describe a case of persistent EPS induced by long-term, intermittent administration of low-dose olanzapine along with metoclopramide for emesis.. A 59-year-old pancreatic cancer patient underwent chemotherapy for 7 months. He was referred to the psychiatry department because of restlessness and insomnia. Although he did not have obvious depressive symptoms, he was anxious about the cancer treatment. For chemotherapy-induced nausea, he had been prescribed 5 mg of olanzapine intermittently for 7 months. He had last used the drug 9 days before presenting it to us. Additionally, he received metoclopramide and palonosetron as antiemetics. We considered akathisia and cancer-related anxiety/agitation as possible causes of restlessness and insomnia, and prescribed clonazepam. However, his symptoms worsened, resulting in hospitalization. We reconsidered his symptoms as cancer-related anxiety/agitation and prescribed quetiapine. Although it was effective, he had tremors and was assessed by a neurologist. Considering the clinical manifestations of rigidity, postural reflex disorder, and a mask-like face, we suspected drug-induced parkinsonism and replaced quetiapine with biperiden on the next day, leading to his discharge after 2 weeks. He did not have symptom recurrence even after discontinuation of biperiden.. Long-term, intermittent administration of low-dose antipsychotics with other antiemetics having D2 receptor antagonism can cause prolonged EPS. Especially in cancer patients, who often require polypharmacy, clinicians should consider exacerbated adverse effects due to drug interactions.

Topics: Antiemetics; Antineoplastic Agents; Antipsychotic Agents; Biperiden; Clonazepam; Dopamine; Humans; Male; Metoclopramide; Middle Aged; Olanzapine; Palonosetron; Psychomotor Agitation; Quetiapine Fumarate; Sleep Initiation and Maintenance Disorders; Vomiting

The COVID-19 outbreak has affected millions of people globally and it also has a huge psychological impact. The objective of this case report is to outline the possible effect of the COVID-19 pandemic to the content of delusions in patients with psychosis. Α 34-year-old male with no history of mental disorder, involuntarily hospitalized due to agitation and aggression towards others, experienced grandiose delusions, referential delusions and delusions of passivity. The content of all his delusions was related to the COVID-19 pandemic. His symptoms were not proven to be caused by any physical condition or substance use disorder. He was prescribed olanzapine 10mg bd and lorazepam 2,5mg td and demonstrated significant improvement with a complete subsidence of his symptoms within a week. He was discharged after a total of 13 days with an ICD-10 diagnosis of brief psychotic disorder. At his 6 months follow-up, he reported no psychiatric symptoms. Existing literature indicates a strong relationship between life experiences and the content of delusions. This case report highlights how the stressful life event of the COVID-19 outbreak affected the content of our patient's delusions.

Topics: Adult; Aggression; Anti-Anxiety Agents; Antipsychotic Agents; COVID-19; Delusions; Humans; Involuntary Commitment; Life Change Events; Lorazepam; Male; Olanzapine; Pandemics; Psychomotor Agitation; Psychotic Disorders; Stress, Psychological

Intramuscular medications are commonly used to treat agitation in the emergency department (ED). The purpose of this study is to compare intramuscular droperidol and olanzapine for treating agitation.. This was a prospective observational study of ED patients receiving intramuscular droperidol or olanzapine for acute agitation. The treating physician determined the medication and dose; however, over time drug shortages made either olanzapine (July to September 2019) or droperidol (November 2019 to March 2020) unavailable, creating a natural experiment. The primary outcome was time to adequate sedation, assessed by the Altered Mental Status Scale (AMSS), defined as time to AMSS score less than or equal to 0.. We analyzed 1,257 patients (median age 42 years; 73% men); 538 received droperidol (median dose 5 mg) and 719 received olanzapine (median dose 10 mg). The majority of patients (1,086; 86%) had agitation owing to alcohol intoxication. Time to adequate sedation was 16 minutes (interquartile range 10 to 30 minutes) for droperidol and 17.5 minutes (interquartile range 10 to 30 minutes) for olanzapine (absolute difference -0.7 minutes; 95% confidence interval -2.1 to 0.5 minutes). Adjusted Cox proportional hazard model analysis revealed no difference between groups in time to sedation (hazard ratio for adequate sedation for droperidol compared with olanzapine 1.12; 95% confidence interval 1.00 to 1.25). Patients receiving olanzapine were more likely to receive additional medications for sedation (droperidol 17%; olanzapine 24%; absolute difference -8% [95% confidence interval -12% to -3%]). We observed no difference between drugs regarding adverse effects except for extrapyramidal adverse effects, which were more common with droperidol (n=6; 1%) than olanzapine (n=1; 0.1%).. We found no difference in time to adequate sedation between intramuscular droperidol and olanzapine.

Topics: Adult; Antipsychotic Agents; Droperidol; Emergency Service, Hospital; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Olanzapine; Pharmaceutical Preparations; Prospective Studies; Psychomotor Agitation; Quality Improvement; Time Factors

A 17-year-old man with no significant medical history presented with new-onset seizure activity and altered mental status manifesting as bizarre behaviour, which included rapid pressured and tangential speech, psychomotor agitation, insomnia and delusions. He also had autonomic dysregulation, manifested in labile blood pressures. He had been recently discharged from his first psychiatric hospitalisation. Many studies were performed, including electroencephalogram (EEG), head CT, laboratory work, urine drug screen and lumbar puncture with cerebral spinal fluid studies, which ultimately led to the diagnosis of anti-N-methyl-D-aspartate receptor (NMDAR) autoimmune encephalitis. He was treated with five rounds of plasmapheresis with complete resolution of his altered mental status. This case highlights the importance of being familiar with the presentation of anti-NMDAR autoimmune encephalitis, especially in cases of new-onset mental status changes with psychotic like symptoms, seizure-like activity and autonomic dysregulation as early detection and treatment improves chances of good prognosis with return to baseline cognitive function.

Topics: Adolescent; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Antipsychotic Agents; Autoantibodies; Diagnosis, Differential; Humans; Male; Olanzapine; Plasmapheresis; Psychomotor Agitation

A 41-year-old man with no significant medical history presented with acute behavioural disruption on the background of a 1-day history of severe headache and a 10-day history of dry cough and fever. He was sexually disinhibited with pressured speech and grandiose ideas. His behaviour worsened, necessitating heavy sedation and transfer to intensive care for mechanical ventilation despite no respiratory indication. Investigations confirmed that he was positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neuroimaging and a lumbar puncture were normal. Initial screening for SARS-CoV-2 in the cerebrospinal fluid was negative although no validated assay was available. The patient's mental state remained abnormal following stepdown from intensive care. Psychiatric assessment found features consistent with acute mania, and he was detained under the Mental Health Act. This case indicates the need to consider COVID-19 in a wider series of clinical presentations and to develop a validated assay for SARS-CoV-2 in the cerebrospinal fluid.

Topics: Adult; Affective Symptoms; Betacoronavirus; Cerebrospinal Fluid; Clonazepam; Coronavirus Infections; COVID-19; Diagnosis, Differential; Emergency Medical Services; Headache; Humans; Male; Neuroimaging; Olanzapine; Pandemics; Pneumonia, Viral; Psychiatric Status Rating Scales; Psychomotor Agitation; Psychotic Disorders; Psychotropic Drugs; SARS-CoV-2; Treatment Outcome

Olanzapine is a second-generation antipsychotic increasingly used in emergency medicine for many indications. Literature on its use in children is sparse. Our objectives were to describe the use, safety, and efficacy of olanzapine in pediatric emergency patients.. A structured chart review was performed of patients 18 years old or younger receiving olanzapine from 2007 to 2016 in the emergency department of a pediatric level I trauma center.. A total of 285 children received olanzapine. Mean age was 16.4 years (range, 9-18 years); 121 were male (42.8%). Primary indications for olanzapine included agitation (n = 166, 58.3%), headache (n = 58, 20.4%), nausea/vomiting/abdominal pain (n = 37, 12.5%), unspecified pain (n = 20, 7%), and other (n = 4, 1.4%). Route of olanzapine administration was intramuscular (n = 160, 56%; median dose, 10 mg; range, 2.5-20), intravenous (n = 101, 36%; median dose, 5 mg; range, 1.25-5), and oral (n = 24, 8%; median dose, 10 mg; range, 5-10). For agitated patients, 28 (17%) received another sedative within 1 hour. For headache patients, 5 (8.6%) received another analgesic. For gastrointestinal complaints, 5 patients (13.5%) received another analgesic/antiemetic. Adverse respiratory events were hypoxia (pulse oximetry reading, in percentage, <92%; n = 7, 2.4%), supplemental oxygen placement (n = 9, 3.2%), and intubation (n = 2, 0.7%). No patient died or had a dysrhythmia. One patient experienced dystonia.. Olanzapine seems safe when used for a variety of conditions in pediatric emergency patients. It may be effective for acute agitation, primary headache, and gastrointestinal complaints.

Topics: Administration, Intravenous; Administration, Oral; Adolescent; Age Distribution; Antiemetics; Antipsychotic Agents; Child; Emergency Service, Hospital; Female; Headache; Humans; Hypnotics and Sedatives; Injections, Intramuscular; Male; Olanzapine; Pain; Pediatric Emergency Medicine; Psychomotor Agitation; Retrospective Studies; Trauma Centers; Vomiting

Acute agitation secondary to alcohol intoxication frequently requires parenteral sedatives for patient and caregiver safety. Antipsychotics play a prominent role; however, no consensus exists regarding the ideal agent. One important consideration when evaluating the choice of antipsychotic is its association with emergency department (ED) length of stay (LOS).. We sought to determine the median ED LOS for patients receiving a single parenteral dose of an antipsychotic for acute agitation secondary to alcohol intoxication in an urban Level I trauma center.. This was a retrospective review of patients receiving a single parenteral dose of droperidol, haloperidol, or olanzapine who were acutely intoxicated on alcohol from 2011 to 2016. Patients needing psychiatric assessment in our ED are discharged to a geographically separate department; thus, ED LOS is minimally impacted by waits for psychiatric assessment. Data were abstracted from the electronic medical record and are presented descriptively.. A total of 40,601 patients were identified and screened; 24,319 patients were intoxicated but received no sedation. Of those remaining 4,495 received multiple drugs and/or benzodiazepines leaving 11,787 for analysis. Median age was 42 years, 76% were male, and 5% of patients were admitted. Mean breath ethanol concentration was 227 mg/dL. Antipsychotics administered were as follows: droperidol (n = 3,790), haloperidol (n = 1,449), and olanzapine (n = 6,548). Median ED LOS was shortest for droperidol (499 minutes, 95% confidence interval [CI] = 493-506 minutes), which was significantly shorter than both haloperidol (524 minutes, 95% CI = 515-537 minutes) and olanzapine (533 minutes, 95% CI = 528-539 minutes). No cases of sudden cardiac death occurred.. Droperidol, when given as monotherapy for sedation of acute agitation secondary to alcohol intoxication, was associated with significantly shorter ED LOS than either parenteral haloperidol or parenteral olanzapine. No difference in ED LOS was observed between haloperidol and olanzapine.

Topics: Adult; Alcoholic Intoxication; Antipsychotic Agents; Droperidol; Drug Delivery Systems; Emergency Service, Hospital; Female; Haloperidol; Humans; Length of Stay; Male; Middle Aged; Olanzapine; Psychomotor Agitation; Retrospective Studies

Rapid treatment of agitation in the emergency department (ED) is critical to avoid injury to patients and providers. Treatment with intramuscular antipsychotics is often utilized, but there is a paucity of comparative effectiveness evidence available.. The purpose of this investigation was to compare the effectiveness of droperidol, olanzapine, and haloperidol for treating agitation in the ED.. This was a retrospective observational study of adult patients who received intramuscular medication to treat agitation. Patients were classified based on the initial antipsychotic they received. The primary effectiveness outcome was the rate of additional sedation administered (rescue medication) within 1 h. Secondary outcomes included rescue sedation for the entire encounter and adverse events.. There were 15,918 patients included (median age 37 years, 75% male). Rescue rates at 1 h were: 547/4947 for droperidol (11%, 95% confidence interval [CI] 10-12%), 988/8825 olanzapine (11%, 95% CI 10-12%), and 390/2146 for haloperidol (18%, 95% CI 17-20%). Rescue rates for the entire ED encounter were: 832/4947 for droperidol (17%, 95% CI 16-18%), 1665/8825 for olanzapine (19%, 95% CI 18-20%), and 560/2146 for haloperidol (26%, 95% CI 24-28%). Adverse events were uncommon: intubation (49, 0.3%), akathisia (7, 0.04%), dystonia (5, 0.03%), respiratory arrest (1, 0.006%), and torsades de pointes (0), with no significant differences between drugs.. Olanzapine and droperidol lead to lower rates of rescue sedation at 1 h and overall, compared with haloperidol. There were no significant differences in major adverse events.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Droperidol; Emergency Service, Hospital; Female; Haloperidol; Humans; Hypnotics and Sedatives; Injections, Intramuscular; Male; Midazolam; Middle Aged; Minnesota; Olanzapine; Psychomotor Agitation; Retrospective Studies

This case report aims to highlight the challenges faced by mental health clinicians in managing complex medical and psychiatric presentation, with a particular interest in intravenous (IV) olanzapine use outside the emergency department (ED) and intensive care unit setting.. There is no current prescribing guideline regarding the use of IV olanzapine for acute agitation associated with schizophrenia and bipolar disorder. Most of the literature available regarding the use of IV olanzapine has originated from studies performed in the ED setting, with the majority of studies reporting a favourable efficacy and safety profile for IV olanzapine. Further research on the utilization of IV olanzapine in the general medical ward is required. Until more data is available, use of IV olanzapine in the acute arousal setting on a general medical ward remains off-label.

Topics: Administration, Intravenous; Antipsychotic Agents; Humans; Male; Middle Aged; Olanzapine; Psychomotor Agitation; Psychotic Disorders

Agitation in the emergency department (ED) can pose a threat to patient and provider safety; therefore, treatment is indicated. The purpose of this study is to compare haloperidol, olanzapine, midazolam, and ziprasidone to treat agitation.. This was a prospective observational study of consecutive patients receiving intramuscular medication to treat agitation in the ED. Medications were administered according to an a priori protocol in which the initial medication given was predetermined in the following 3-week blocks: haloperidol 5 mg, ziprasidone 20 mg, olanzapine 10 mg, midazolam 5 mg, and haloperidol 10 mg. The primary outcome was the proportion of patients adequately sedated at 15 minutes, assessed with the Altered Mental Status Scale.. Seven hundred thirty-seven patients were enrolled (median age 40 years; 72% men). At 15 minutes, midazolam resulted in a greater proportion of patients adequately sedated (Altered Mental Status Scale <1) compared with ziprasidone (difference 18%; 95% confidence interval [CI] 6% to 29%), haloperidol 5 mg (difference 30%; 95% CI 19% to 41%), haloperidol 10 mg (difference 28%; 95% CI 17% to 39%), and olanzapine (difference 9%; 95% CI -1% to 20%). Olanzapine resulted in a greater proportion of patients adequately sedated at 15 minutes compared with haloperidol 5 mg (difference 20%; 95% CI 10% to 31%), haloperidol 10 mg (difference 18%; 95% CI 7% to 29%), and ziprasidone (difference 8%; 95% CI -3% to 19%). Adverse events were uncommon: cardiac arrest (0), extrapyramidal adverse effects (2; 0.3%), hypotension (5; 0.5%), hypoxemia (10; 1%), and intubation (4; 0.5%), and occurred at similar rates in each group.. Intramuscular midazolam achieved more effective sedation in agitated ED patients at 15 minutes than haloperidol, ziprasidone, and perhaps olanzapine. Olanzapine provided more effective sedation than haloperidol. No differences in adverse events were identified.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Cohort Studies; Emergency Medical Services; Female; Haloperidol; Humans; Injections, Intramuscular; Male; Mental Status and Dementia Tests; Midazolam; Middle Aged; Olanzapine; Piperazines; Prospective Studies; Psychomotor Agitation; Thiazoles; Treatment Outcome; Young Adult

Parenteral olanzapine is an emerging therapy for a variety of conditions in the emergency department (ED). Intramuscular administration is standard; however, intravenous administration has been proposed as a safe alternative route. We investigate the safety and efficacy of both intramuscular and intravenous olanzapine in the ED when used for a variety of indications.. This was a prospective observational study of patients presenting to an urban Level I trauma center ED. Trained research associates screened the ED for patients receiving parenteral olanzapine. The primary outcome of the study was incidence of respiratory depression measured with standard markers. Secondary outcomes included use of additional doses or sedatives, corrected QT interval (QTc) data, time to nadir sedation, adverse events, and physician assessment of efficacy.. There were 784 patients included in the final analysis. Intravenous olanzapine was administered to 295 patients; 489 received intramuscular olanzapine. Respiratory depression occurred in 11 of 295 patients (3.7%; 95% confidence interval [CI] 1.6% to 5.9%) receiving intravenous olanzapine and 10 of 489 (2.0%; 95% CI 0.8% to 3.3%) receiving intramuscular olanzapine. Seven patients required intubation, 2 in the intravenous group and 5 in the intramuscular group. Nonrespiratory complications occurred in 8 patients, 6 of 295 (2.0%; 95% CI 0.4% to 3.6%) in the intravenous group and 2 of 489 (0.4%; 95% CI 0% to 0.96%) in the intramuscular group. Dysrhythmias were isolated to 2 episodes of bradycardia requiring only supportive care.. These data suggest that, with proper monitoring, administration of olanzapine, both intramuscular and intravenous, is safe for several indications in the ED.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Conscious Sedation; Emergency Service, Hospital; Female; Humans; Injections, Intramuscular; Injections, Intravenous; Male; Middle Aged; Olanzapine; Prospective Studies; Psychomotor Agitation; Respiratory Insufficiency; Young Adult

Olanzapine is an atypical antipsychotic with similar pharmacologic properties to droperidol. Due to the current droperidol shortage, the authors' clinical practice has been to substitute olanzapine for droperidol in many situations. At this time, olanzapine is U.S. Food and Drug Administration approved for oral and intramuscular (IM) use only, but due to its increased utility, intravenous (IV) olanzapine was recently approved for use in the study emergency department (ED).. The authors sought to review the use and safety of IV olanzapine in the ED patient population.. A retrospective review of consecutive patients receiving IV olanzapine between January 1, 2014, and July 1, 2014, was conducted. Data were collected via an electronic medical record review. The study was deemed exempt from informed consent by our institutional review board.. A total of 713 patients received IV olanzapine during the study period. The median age was 38 years (range = 18 to 85 years), and 313 patients were male (43.9%). Primary indications for IV olanzapine administration included acute agitation (n = 245, 34.4%), abdominal pain (n = 165, 23.1%), headache (n = 121, 17.0%), nausea and vomiting (n = 107, 15.0%), pain (other; n = 60, 8.4%), and unknown (n = 15, 2.1%). IV dosing varied: 1.25 mg (n = 20, 2.8%), 2.5 mg (n = 185, 25.9%), 5 mg (n = 507, 71.1%), and 10 mg (n = 1, 0.1%). Forty-nine patients required a second dose of olanzapine (22 IV, 26 IM, one oral). The maximum total dose of olanzapine was 20 mg. Ninety-eight patients required a total of 146 doses of additional sedatives during their ED course. Other sedative medications included ketamine (n = 17, 2.4%), haloperidol (n = 48, 6.7%), and benzodiazepines (n = 81, 11.4%). Hypoxia was noted in 74 patients (10.4%). Major respiratory complications, including airway stimulation or repositioning maneuvers and intubation, occurred in 15 patients (2.1%). After consensus review, one intubation was classified as "likely related" to olanzapine administration, and two were classified as "possibly related" to olanzapine. Akathisia likely occurred in four patients (0.6%), and no allergic reactions were identified. Electrocardiograms (ECGs) were performed in 322 patients. A total of 251 patients had an ECG performed before olanzapine administration (median QTc = 404 ms), and 88 patients had an ECG performed after olanzapine administration (median QTc = 415 ms). Acute alcohol and drug intoxication was common, 118 (16.5%) patients were positive for ethanol, and seven of 23 drug screens were positive for sympathomimetics. Thirty-four of 284 admissions (4.5%) were to intermediate or intensive care unit beds. No patients died while in the ED and no cases of sudden cardiac death were noted.. In this large retrospective review, IV olanzapine appears to be a safe in the management of a variety of ED indications. Hypoxia was common, but serious airway compromise was rare.

Topics: Administration, Intravenous; Adult; Antipsychotic Agents; Benzodiazepines; Droperidol; Drug Therapy, Combination; Emergency Service, Hospital; Female; Humans; Hypnotics and Sedatives; Injections, Intramuscular; Male; Middle Aged; Olanzapine; Pain; Psychomotor Agitation; Retrospective Studies; United States; Young Adult

To assess activating and tranquilizing effects of second-generation antipsychotics (SGAs) in youth.. As part of the naturalistic inception cohort study, "Second-generation Antipsychotic Treatment Indication, Effectiveness and Tolerability in Youth (SATIETY)," subjective ratings of activating and tranquilizing symptoms were obtained monthly for 3 months from antipsychotic-naïve youth initiating SGAs using the Treatment Emergent Symptoms Scale (TESS). Discontinuation rates, and TESS-reported symptom rates, and severity were related to clinical and treatment parameters. Two compound measures of TESS were defined: presence of any daytime activating (ACTIVATION+) and sedating symptoms (SEDATION+).. In 327 antipsychotic-naïve youth originally initiating the four studied SGAs, discontinuation due to sedation was marginally highest with quetiapine (13.0%) followed by olanzapine (7.3%), risperidone (4.2%), and aripiprazole (2.0%) (p = 0.056). Two hundred fifty-seven antipsychotic-naïve youth (13.8 ± 3.6 years, male = 57.8%) initiated aripiprazole (n = 40), olanzapine (n = 45), quetiapine (n = 36), or risperidone (n = 135) and completed ≥1 postbaseline follow-up visit. Baseline prevalence of ACTIVATION+ (39.9%) or SEDATION+ (54.1%) did not differ between SGAs. Rates of both compound measures changed significantly over time (decrease for ACTIVATION+, p = 0.0002; increase for SEDATION+, p < 0.0001) with slight differences between SGAs, explained by lower rates of ACTIVATION+ with olanzapine (p = 0.002) and slightly higher rates of ACTIVATION+ with aripiprazole (p = 0.018) during follow-up, and lower rates of SEDATION+ with aripiprazole (p = 0.018). All four SGAs reduced insomnia (p = 0.001) and increased hypersomnia (p < 0.001). Postbaseline prevalence of drowsiness, the most frequent, but mild TESS complaint was 85%, without SGA differences. Younger age was associated with activating symptoms, higher age with sedating symptoms, and lower baseline functioning increased both. Psychomotor retardation rates were high in subjects with schizophrenia-spectrum disorders, whereas stimulant comedication was associated with psychomotor activation, regardless of diagnosis.. Although small SGA-specific differences in activating/sedating compound side effect measures were noted, independent predictors of single TESS ratings included clinical parameters, rather than specific SGAs, suggesting a need for carefully individualized treatment strategies.

Topics: Adolescent; Aripiprazole; Arousal; Benzodiazepines; Child; Cohort Studies; Female; Humans; Male; Olanzapine; Patient Outcome Assessment; Psychomotor Agitation; Quetiapine Fumarate; Risperidone; Schizophrenia, Childhood; Schizophrenic Psychology; Wakefulness

A major medical problem for patients undergoing electroconvulsive therapy (ECT) is the occurrence of postictal agitation (PIA). This phenomenon is associated with confusion and disorientation that can have severe clinical implications for the safety of the patient and health care professionals. Many different pharmacological strategies have been used to prevent PIA. We present data on 40 patients who suffered from PIA after a course of ECT and evaluate the prophylactic use of orally disintegrating olanzapine in the prevention of PIA in subsequent ECT treatments.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder, Major; Electroconvulsive Therapy; Female; Humans; Male; Middle Aged; Olanzapine; Psychomotor Agitation; Psychotic Disorders; Treatment Outcome; Young Adult

Schizophrenia is a chronic mental disorder related to hypo-functioning of glutamatergic neurotransmission. N-methyl-D-aspartate-receptor (NMDA-R) positive modulators were reported to reduce schizophrenia symptoms. However, their efficacy is low and inconsistent. We developed a novel antipsychotic possessing an olanzapine moiety linked to the positive modulator of glutamate NMDA-R sarcosine (PGW5) and characterized the pharmacodynamic properties of the novel molecule in-vivo using MK-801 and in-vitro using receptor binding analysis. We investigated the pharmacological activity of PGW5 (olanzapine linked to sarcosinyl moiety) in male mice (BALB/c or C57BL). In an open field test, up to 50mg/kg PGW5 did not affect motility while higher doses were sedative. PGW5 (25-50mg/kg po) antagonized MK-801 (0.15 mg/kg ip) and amphetamine-induced (5mg/kg ip) hyperactivity. PGW5 (25mg/kg po/d) treatment for 15 or 22 days exhibited antidepressant and anxiolytic activity in mice. Moreover, PGW5, but not olanzapine, attenuated phencyclidine (PCP)-induced deficits of social preference in mice and promoted the expression of brain derived neurotrophic factor (BDNF) in the hippocampus and the frontal cortex and glutamic acid decarboxylase (GAD67) in the hippocampus. Mice treated with PGW5 (25 and 50mg/kg/d) for 28 days did not show toxic effects in terms of weight gain and blood-chemistry analysis.. PGW5 is a novel and safe antipsychotic, efficacious against schizophrenia-like positive and negative symptoms at nonsedative doses. The drug shows anxiolytic and antidepressant activity, and improves impaired social performance in phencyclidine (PCP) treated mice. The mechanism underlying its activity seems to involve potentiation of NMDA receptor as well as stimulation of brain BDNF and GAD67 expression.

Topics: Alanine; Amphetamine; Animals; Antipsychotic Agents; Anxiety; Benzodiazepines; Brain; Central Nervous System Stimulants; Depression; Dizocilpine Maleate; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Excitatory Amino Acid Antagonists; Exploratory Behavior; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Motor Activity; Olanzapine; Phencyclidine; Psychomotor Agitation; Schizophrenia; Social Behavior

Although the number of patients admitted for psychiatric emergency care is increasing according to data from various countries, there are no large-scale studies assessing clinical emergency practice and in several countries no national guidelines have been published concerning emergency care in psychiatry. The aim of our study was to assess practice related to emergency care of agitated-psychotic patients in Hungary.. Anonymous survey questionnaire with questions related to care of an agitated patient showing psychotic symptoms was dispatched to 210 institutions providing psychiatric care in Hungary in 2013.. The overwhelming majority of the 155 participating clinicians would use haloperidol (92.9%) and benzodiazepines (81.3%), 74.8% in a dual combination. 18.7% would apply monotherapy and 5.2% a triple combination of medications. 59.4% would use i.v. and 23.9% i.m. therapy, and 9% would apply the combination of these two. In case of failure of first-line therapy, 76.8% of participants would repeat the previous medication.. The aim of our study was to assess emergency interventions in psychiatry focusing on different psychopharmacological approaches. Our results provide a cross-sectional view on current practice in Hungary, and therefore may contribute to outlining practice-coherent guidelines and also provide the opportunity for a comparison with international trends.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clopenthixol; Droperidol; Drug Prescriptions; Drug Therapy, Combination; Emergency Treatment; Female; Haloperidol; Humans; Hungary; Male; Middle Aged; Olanzapine; Piperazines; Practice Patterns, Physicians'; Promethazine; Psychiatry; Psychomotor Agitation; Psychotic Disorders; Quinolones; Surveys and Questionnaires

Many patients with Lewy body dementia develop visual hallucinations and other psychiatric symptoms. These patients are hypersensitive to antipsychotic drugs. Although patients tolerate atypical better than typical antipsychotics, both types can cause major extrapyramidal side effects. The anticonvulsant mood stabilizer topiramate, which does not cause parkinsonism, has been used as adjuvant therapy for both the positive and negative symptoms of schizophrenia; these symptoms can resemble those of Lewy body dementia. This report documents a 65-year-old woman with a 3-year history of progressive dementia that over the past 2 years had become complicated by severe extrapyramidal symptoms and agitated hallucinations. Her hallucinations became daily and were disrupting to her family. She was given a clinical diagnosis of Lewy body dementia after imaging and laboratory studies ruled out other etiologies. Treatment with olanzapine relieved her psychotic symptoms but caused severe dystonias, daily myoclonic jerks, and tremors. Stopping the olanzapine and starting topiramate 25 mg daily eliminated the hallucinations and agitation without worsening her extrapyramidal side effects. However, the topiramate was stopped because the patient reportedly developed anorexia and significant weight loss. Her hallucinations returned. When topiramate was reinstated at 12.5 mg a day, her agitation resolved, although her hallucinations continued. After 6 months on this dose, her agitation was still fairly well controlled without serious side effects or worsening of her parkinsonian symptoms.

Topics: Aged; Anticonvulsants; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Female; Fructose; Hallucinations; Humans; Lewy Body Disease; Neuroprotective Agents; Olanzapine; Psychomotor Agitation; Schizophrenia; Topiramate; Treatment Outcome

As much as the ideal treatment goal for severe mental illnesses such as bipolar disorder and schizophrenia is to prevent or delay the recurrence or relapse of acute episodes, when the patient presents with an acute episode, the goal should be to manage behavioural symptoms, and return to prior levels of symptomatic control. In a serious mental illness, the management of the acutely agitated state may require rapid tranquillisation (RT) to control violent and/or disturbed behaviour when all other methods of de-escalation have failed. Current clinical practice guidelines for emergency interventions in the case of acutely disturbed behaviours favour calming the patient by reducing agitation with mild sedation, but not sleep, to allow continued interaction with the patient, to ensure an accurate diagnosis, and to enable patients to be actively engaged in treatment decisions. Pharmacotherapy is an essential element in RT and the available agents used may be unique and separate from the patient's regular course of treatment, primarily because agents used in RT may not be suitable for long-term treatment due to an unfavourable efficacy and safety profile. Therefore, the choice of pharmacotherapy is essential to achieve an effective RT and a smooth transition to standard care and routine daily life for the patient. Of the available agents for RT, aripiprazole demonstrated a favourable efficacy and safety profile both over the short-term - including in its intramuscular form (IM) - and in the long-term treatment of bipolar I disorder and schizophrenia. The objective of this article is to assess the available clinical data on IM aripiprazole as a treatment option for the rapid control of agitation and disturbed behaviours in these conditions and to provide a consensus statement based on the expertise of UK healthcare practitioners in acute treatment units.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Haloperidol; Humans; Hypnotics and Sedatives; Olanzapine; Piperazines; Psychomotor Agitation; Quinolones; Schizophrenia; Tranquilizing Agents

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

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

Agitation has significant consequences for patients and staff. When verbal techniques fail, expert guidelines recommend the use of second-generation antipsychotics (SGAs). Perhaps out of familiarity with haloperidol and benzodiazepines, emergency department (ED) clinicians often pair SGAs with benzodiazepines as well. Use of SGAs such as olanzapine in alcohol-intoxicated (ETOH+) patients or with benzodiazepines is not well studied and may be associated with vital sign abnormalities.. This is a structured chart review of all patient visits who received either oral or intramuscular (i.m.) olanzapine in an academic ED from 2004 to 2010 and who had systolic blood pressure, heart rate, and oxygen saturation documented before medication administration and within 4 hours afterwards.. Four hundred eighty-two patient visits received olanzapine; 275 patient visits (225 oral, 50 i.m.) had vital signs documented. Neither route of administration, concurrent benzodiazepines, nor ingestion of ETOH were associated with significant decreases in systolic BP or heart rate (P = ns for all comparisons). Decreases in oxygen saturations, however, were significantly larger in ETOH+ patients who received i.m. olanzapine or i.m. olanzapine + benzodiazepines. Route of administration, concurrent benzodiazepines, nor ingestion of ETOH was associated with significant decreases in systolic blood pressure or heart rate (p = ns for all comparisons). Decreases in oxygen saturations, however, were significantly larger in ETOH+ patients who received i.m. olanzapine or i.m. olanzapine + benzodiazepines.. Oral olanzapine was not associated with significant vital sign changes in ED patients. Intramuscular olanzapine also was not associated with vital sign changes in ETOH- patients. In ETOH+ patients, i.m. olanzapine was associated with significant oxygen desaturations. In ETOH+ ED patients, oral olanzapine (with or without benzodiazepines) or haloperidol may be safer choices. ETOH+ patients may have differential effects with the use of i.m. SGAs such as olanzapine and should be studied separately in drug trials.

Topics: Administration, Oral; Adult; Alcoholic Intoxication; Antipsychotic Agents; Benzodiazepines; Blood Pressure; Drug Interactions; Emergency Service, Hospital; Female; Heart Rate; Humans; Hypnotics and Sedatives; Injections, Intramuscular; Male; Olanzapine; Oxygen; Psychomotor Agitation; Retrospective Studies

A retrospective cohort study was conducted to determine if there is an association between short-acting intramuscular (SAIM) antipsychotics used for acute agitation and length of stay (LOS). Patients with a diagnosis of schizophrenia or schizoaffective disorder who were dispensed at least one dose of a SAIM antipsychotic were divided into groups based on the initial SAIM antipsychotic received once admitted to a psychiatric unit. Electronic records were used to gather demographic information, LOS, and number of injections received during an admission. Cost was calculated from the number of injections received. One-hundred and thirty-six patients were enrolled. When comparing the haloperidol group to the second generation antipsychotic group, there was no statistically significant difference, in LOS 16.98 ± 9.56 days versus 17.59 ± 11.52 days (P = 0.75), respectively. There was a statistically significant difference in both cost and number of injections between groups, favoring the haloperidol group. Ziprasidone was associated with a shorter LOS compared with olanzapine, 13.57 and 19.10 days, respectively (P = 0.026). Patient characteristics should be evaluated when determining an agent for acute agitation. However, because literature indicates second generation SAIM antipsychotics are only noninferior to haloperidol; other factors should also be evaluated; including impact on LOS and impact on hospital resources. This study indicates use of a second generation SAIM antipsychotic for acute agitation is more costly, requires more injections, and was not associated with a shorter length of stay when compared with SAIM haloperidol.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Cohort Studies; Drug Costs; Female; Haloperidol; Humans; Injections, Intramuscular; Length of Stay; Male; Middle Aged; Olanzapine; Piperazines; Psychomotor Agitation; Quinolones; Retrospective Studies; Schizophrenia; Thiazoles

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

Akathisia is a syndrome characterized by the unpleasant sensation of "inner" restlessness that manifests itself in the inability of sitting still or not moving. Many types of medicaments can cause akathisia as an adverse event of their use and they include: antipsychotics, antidepressants, antiemetics, antihistamines, and psychoactive substances. We will present the case of a 50 year old patient, treated on two occasions for psychotic depression. During the second hospitalization it is possible that antipsychotic treatment combined with an antidepressant caused akathisia or there were symptoms of agitated depression and akathisia present at the same time, which is very difficult to determine in everyday clinical practice. We can conclude that in this case, as in many others, akathisia as a possible adverse effect of psychopharmacs was very hard to identify. Therefore, it is necessary to have akathisia in mind when using certain medicaments, especially when combining several that use the same enzymatic system and consequently raise levels of at least one of them.

Topics: Affective Disorders, Psychotic; Akathisia, Drug-Induced; Anticonvulsants; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Benzodiazepines; Depressive Disorder; Diagnosis, Differential; Diagnostic Errors; Dibenzothiazepines; Drug Interactions; Drug Therapy, Combination; Fluvoxamine; Humans; Male; Middle Aged; Olanzapine; Psychomotor Agitation; Quetiapine Fumarate; Valproic Acid

Psychiatry is awash with pharmacological acute behavioural disturbance protocols which list oral or intramuscular benzodiazepines and antipsychotics with numerous options. This results in frequent over-sedation and occasional profound sedation and death. This paper describes the development of a simplified sedation protocol for the pharmacological management of acute behavioural disturbance.. Following the wider availability of intramuscular lorazepam in 2008, Metro North Mental Health developed a protocol utilizing only two products - oral or intramuscular lorazepam or olanzapine - which was subsequently developed into a statewide protocol.. The advantage of utilizing only two sedating medications is that it greatly reduces the risk of profound sedation and theoretically reduces the risk of other complications including deaths. Clinical staff who have utilized the protocol report a reduction in over-sedation of inpatients.. A simplified protocol makes the pharmacological management of acute behaviour disturbance safer for both patients and staff.

Topics: Administration, Oral; Antipsychotic Agents; Benzodiazepines; Clinical Protocols; Humans; Injections, Intramuscular; Lorazepam; Olanzapine; Psychomotor Agitation

Olanzapine is a second generation antipsychotic of thienobenzodiazepin group, which is used in the treatment of schizophrenia, bipolar disorder, and others, mainly psychiatric. Its multireceptor action (antagonism to dopaminergic D1, D2, D4, serotoninergic 5-HT2A, 5-HT2C, histaminergic H1, cholinergic M1-5, and a1--adrenergic receptors) results in multiple clinical symptoms in the course of acute poisoning.. Evaluation of incidence and intensity of clinical symptoms in patients with of acute olanzapine intoxication. The pathophysiological mechanisms of particular symptoms are also described.. 26 patients (mean age 37.7 +/- 15.3 years) hospitalized in 2005-2008 in toxicological centers in Krakow and Gdansk because of acute olanzapine poisoning (all patients had the toxic serum level of olanzapine above 100 ng/mL). The study group consisted of 11 men (29.3 +/- 8.5 years) and 13 women (44.9 +/- 16.4 years); 1 man and 1 woman were poisoned twice.. Prospective analysis (using descriptive statistics) of data taken from medical anamnesis and results of physical examination, considering the following ones: consciousness disturbances (Glasgow Coma Scale, Matthew's scale, qualitative disturbances), vital signs (arterial blood pressure, heart rate, breathing rate, temperature), neurological findings (muscular tension, tendon reflexes, extrapyramidal symptoms, pupils) and others (oral and bronchial secretion, Poisoning Severity Score).. The mean dose of ingested olanzapine in the study group was 352.5 +/- 220.0 mg, while the mean time since ingestion to hospital admission was 4.4 +/- 3.5 h. The half of the patients took other medicines together with olanzapine, and 23% consumed alcohol, as well. The following intensity of quantitative consciousness disturbances according to Matthew's scale were observed: grade 0 - 8%, I - 15%, II - 23%, III - 50%, and IV - 4%. The minimal and maximal values of blood pressure were: 102/63 +/- 16/14 and 163/ 97 +/- 27/18 mmHg, respectively; heart rate: 77 +/- 15 and 138 +/- 22 beats/min; temperature: 36.3 +/- 0.5 and 37.9 +/- 0.8 degrees C; breathing rate in non-intubated patients: 14 +/- 2 and 22 +/- 7 breaths/min. The mean duration of consciousness disturbances, endotracheal intubation and mechanical ventilation were: 44.9 +/- 31.3; 22.0 +/- 33.3 and 7.0 +/- 25.9 h, respectively. The study revealed tachycardia (85%), psychomotor agitation (81%), hypertension (73%), miosis (65%), and coma (54%) as the most common symptoms of poisoning. The hospitalization of poisoned patients lasted on average 5.7 +/- 3.6 days and the half of them were poisoned severely (PSS 3).. In the course of acute olanzapine poisoning: (1) the prevailing symptoms come from circulatory and central nervous systems; (2) some symptoms are mutually opposed, eg.: coma - psychomotor agitation, hypertension - hypotension, tachycardia - bradycardia, hyperthermia - hypothermia, miosis - mydriasis; (3) rarely consciousness disturbances may persist for up to 6 days after olanzapine overdose; (4) the course of poisoning can be severe, sometimes complicated, but fatal outcomes are rare.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Coma; Drug Overdose; Female; Hospitalization; Humans; Hypertension; Male; Miosis; Olanzapine; Poisoning; Poland; Psychomotor Agitation; Tachycardia

Agitation is a medical emergency with increased risk for poor outcome. Successful treatment often requires intramuscular (IM) psychotropics. Safety data from the first 21 months of olanzapine IM, approved in the United States for the treatment of agitation associated with schizophrenia and bipolar disorder, are presented.. A Lilly-maintained safety database was searched for all spontaneous adverse events (AEs) reported in temporal association with olanzapine IM treatment.. The estimated worldwide patient exposure to olanzapine IM from January 1, 2004, through September 30, 2005, was 539,000; 160 cases containing AEs were reported from patients with schizophrenia (30%), bipolar disorder (21%), unspecified psychosis (10%), dementia (8%), and depression (5%). Many reported concomitant treatment with benzodiazepines (39%) or other antipsychotics (54%). The most frequently reported events involved the following organ systems: central nervous (21%), cardiac (12%), respiratory (6%), vascular (6%), and psychiatric (5%). Eighty-three cases were considered serious, including 29 fatalities. In these fatalities, concomitant benzodiazepines or other antipsychotics were reported in 66% and 76% of cases, respectively. The most frequently reported events in the fatal cases involved the following organ systems: cardiovascular (41%), respiratory (21%), general (17%), and central nervous (10%). The majority of fatal cases (76%) included comorbid conditions and potentially clinically significant risk factors for AEs.. Clinicians should use care when treating agitated patients, especially when they present with concurrent medical conditions and are treated with multiple medications, which may increase the risk of poor or even fatal outcomes. Clinicians should use caution when using olanzapine IM and parenteral benzodiazepines simultaneously.

Topics: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Child; Databases as Topic; Fatal Outcome; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Olanzapine; Psychomotor Agitation; Risk Factors; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

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

Topics: Aggression; Antipsychotic Agents; Benzodiazepines; Electroconvulsive Therapy; Female; Humans; Hyperkinesis; Intellectual Disability; Olanzapine; Parkinson Disease, Secondary; Psychomotor Agitation; Young Adult

Topics: Antipsychotic Agents; Benzodiazepines; Drug Therapy, Combination; Emergency Service, Hospital; Humans; Injections, Intravenous; Olanzapine; Psychomotor Agitation; Retrospective Studies; Victoria

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: Administration, Oral; Antipsychotic Agents; Benzodiazepines; Diagnostic and Statistical Manual of Mental Disorders; Emergency Medical Services; Humans; Informed Consent; Injections, Intramuscular; Mental Disorders; Olanzapine; Prospective Studies; Psychiatric Status Rating Scales; Psychomotor Agitation; Severity of Illness Index; Treatment Refusal

Antipsychotics have long been used to treat agitation and psychosis related to Alzheimer's disease, but in a limited fashion because of troubling adverse effects. The new atypical antipsychotics are thought to be at least as effective as first-generation drugs and to cause fewer adverse effects. These drugs, however, are currently not US FDA-approved for use among elderly demented subjects due to a slight increase in the risk of death and serious cardiovascular events within this population. However, their favourable adverse effect profile has led many physicians to prescribe these drugs as first-line therapy for behaviourally disturbed patients with Alzheimer's disease. Clinical trials to evaluate the use of atypical antipsychotics have produced varying results, and clarity has not yet been achieved. Thus, a quantitative summary of the risks and benefits may help inform complex decisions that must be made in this area. In this study we set out to compare the expected costs and outcomes for a community-dwelling cohort of patients with Alzheimer's disease with agitation and/or psychosis who are (a) untreated, or (b) treated with olanzapine.. We constructed a Markov state-transition model using the best published data from several sources for Alzheimer's disease patient progression and treatment. This model allowed us to compare the expected costs and outcomes associated with olanzapine treatment compared with no treatment for a synthetic cohort of US adults aged > or =65 years. The model cycles every 6 months and continues until all patients die from Alzheimer's disease progression or from co-morbid conditions. Outcome estimates included the incremental cost-effectiveness ratio (ICER) and cost per quality-adjusted life-year (QALY) gained. The robustness of the estimates was examined by sensitivity analyses of key parameters, including cost of care, olanzapine effectiveness and Alzheimer's disease progression rates.. Results indicated that olanzapine was a cost-effective treatment for agitation and psychosis related to Alzheimer's disease when compared with no treatment (ICER <$US50,000). In addition, sensitivity analyses demonstrated that olanzapine remained cost effective despite multiple variations of several parameters, both alone and concurrently.. Olanzapine treatment for agitation and psychosis related to Alzheimer's disease is cost effective when compared with no treatment. Further analysis should be performed as atypical antipsychotics become generic, as more information on health utilities in the Alzheimer's disease population becomes available, and to compare atypical antipsychotics with first-generation antipsychotics.

Topics: Aged; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Cohort Studies; Cost-Benefit Analysis; Drug Costs; Ethnicity; Humans; Markov Chains; Mortality; Olanzapine; Proportional Hazards Models; Psychomotor Agitation; Psychotic Disorders; Quality-Adjusted Life Years; Treatment Outcome; United States

Topics: Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Humans; Olanzapine; Psychomotor Agitation; Quetiapine Fumarate; Risperidone

The use of atypical antipsychotics (AA) is suggested in the treatment of BPSD, although controversial data are available on their safety and efficacy. The aim of this study was to assess the efficacy and safety of AA and whether this therapy could modify cognitive and functional domains in parallel with BPSD modifications. Out of 1,100 patients followed by the psychogeriatric ambulatory of our hospital, 69 patients (6.2%) were in therapy with AA and only 32 of them fulfilled the inclusion criteria of this study. Namely, the availability was required of a complete geriatric assessment, including the evaluation of cognitive (mini mental state examination=MMSE), emotional (the Italian "scala di valutazione del benessere emotivo nell'anziano"=SVEBA), functional (basic and instrumental activities of daily living=ADL and IADL), as well as behavioral (neuropsychological inventory=NPI) status, at the beginning (T(0)) and after a 6 month therapy (T(1)). The AA prescribed were risperidone (42.8%), olanzapine (31.3%), quetiapine (25.9%). The mean age was 80.1 years; 34.4% male; 65.6% female. Educational level was elementary in 90.6% of cases. Only 21.9% were institutionalized. 15.6% had 1 cardiovascular risk factor (CVRF), 50% more than 1, and the remaining with no CVRF. More than the half of them were diagnosed with degenerative dementia (D) (40.6% Alzheimer D=AD; 15.6% fronto-temporal dementia (FTD); 34.4% with vascular dementia (VD) (9.4%) or combined D (25%); 3,1 % with mild cognitive impairment (MCI), classified as F06.7 by the ICD-10 (International Classification of Diseases) and 6.2% with psychiatric disturbances. The most common BPSD were hallucinations, delusions, agitation, verbal and physical aggression. A paired t-test was applied to analyze data. There was a significant improvement with all 3 AA on NPI (mean NPI T(0)=27.50 vs. T(1)=12.13; t=7.49). An improvement was also observed on SVEBA (t=1.97), close to significance. Most people did not have any adverse effects; 5 patients (15.6%) had extrapyramidal symptoms and 1 (3.1%) showed ginecomasty, clinically so relevant to cause the interruption of the treatment. The profile of safety and efficacy described on the whole sample was confirmed when it was subdivided according to kind of drug, illness severity and presence/absence of CVRF. In a large sample of the "real" subjects attending a geriatric service for dementia, the accurate selection of patients treatable with AA leads to identification of a popula

Topics: Activities of Daily Living; Aged; Antipsychotic Agents; Benzodiazepines; Dementia; Female; Follow-Up Studies; Humans; Institutionalization; Male; Olanzapine; Psychomotor Agitation; Retrospective Studies; Risperidone; Severity of Illness Index

Atypical antipsychotics will continue to be prescribed for the behavioral symptoms of dementia in the absence of more effective, better tolerated, and safer alternatives. The evidence base, although incomplete, suggests that modest treatment effect sizes are offset by risk of considerable adverse effects. How might this information be best applied to clinical practice? Non-pharmacologic strategies should be implemented in routine clinical practice. Placebo-controlled clinical trials of individual antipsychotic agents have historically reported high placebo response rates; CATIE-AD reported that the sum total of the risk/benefit equation of atypical antipsychotic therapy was no greater than that achieved by placebo. CATIE-AD was designed to study the effectiveness of atypical antipsychotic treatment in community dwelling patients with AD. It is uncertain whether the results can be generalized to the populations of dementia patients residing in nursing homes with more severe cognitive and behavioral impairment. There is some suggestion that nursing home patients with dementia complicated by severe behavioral symptoms, particularly agitation and aggression without accompanying psychosis, might achieve greater benefit from atypical antipsychotic treatment than patients with milder behavioral symptoms. The finding that dementia patients without psychosis may respond more robustly to antipsychotic treatment seems counterintuitive, but may support the hypothesis that the neurobiology of the "psychosis of AD" differs from the psychosis of schizophrenia or bipolar disease. Adverse effects associated with antipsychotic therapy should be aggressively monitored throughout therapy. Treatment-emergent sedation was associated with all of the atypical antipsychotics in CATIE-AD and is probably an important mediator of mortality risk in patients with dementia. Sedation exacerbates pre-existing cognitive impairment and increases the risk of complications such as aspiration pneumonia, so concomitant use of benzodiazepines should be discouraged or limited to short periods with careful observation.' Once initiated, the effectiveness and tolerability of antipsychotic therapy should be evaluated routinely. In Alzheimer's disease, the severity and frequency of behavioral symptoms often decreases as illness progresses. In a stable patient, it is prudent to attempt to taper and discontinue the antipsychotic after 2-8 months of therapy. Better understanding of the potential adverse

Topics: Aged; Alzheimer Disease; Antipsychotic Agents; Behavioral Symptoms; Benzodiazepines; Dementia; Dibenzothiazepines; Evidence-Based Medicine; Humans; Olanzapine; Psychomotor Agitation; Quetiapine Fumarate; Retrospective Studies; Risperidone; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Drug Therapy, Combination; Humans; Male; Olanzapine; Piperazines; Psychomotor Agitation; Quinolones; Schizophrenia; Schizophrenic Psychology

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: Adult; Antipsychotic Agents; Benzodiazepines; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Olanzapine; Psychomotor Agitation; Psychotic Disorders; Restraint, Physical

Agitation is relatively common among Borderline Personality Disorder (BPD) patients in Psychiatric Emergency Services (PES). New injectable atypical antipsychotics are indicated for treatment in agitated psychotic or maniac patients but not for agitated BDP patients. Twenty agitated BPD patients were treated with intramuscular atypical antipsychotics (olanzapine or ziprasidone). Results suggest intramuscular atypical antipsychotics may be effective, fast and safe for treating acute BPD patients.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Borderline Personality Disorder; Comorbidity; Emergency Services, Psychiatric; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychomotor Agitation; Psychotic Disorders; Schizophrenia; Thiazoles; Treatment Outcome

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

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Humans; Olanzapine; Piperazines; Psychomotor Agitation; Psychotic Disorders; Quinolones; Risperidone; Thiazoles

Acutely agitated patients with schizophrenia might require treatment with IM antipsychotics, followed by a transition to oral medication.. The aim of this study was to assess the relationship between 24-hour IM and transitional oral dosages of 2 antipsychotic medications, olanzapine and haloperidol.. This post hoc analysis used data from a multinational, double-blind, randomized, placebo-controlled study comparing the efficacy of olanzapine, haloperidol, and placebo in acutely agitated inpatients aged > or =18 years with schizophrenia conducted at hospitals in 13 countries. Patients received 1 to 3 IM injections of olanzapine 10 mg or haloperidol 7.5 mg over 24 hours (IM phase), followed by 4 days of oral treatment with 5 to 20 mg/d of either antipsychotic (oral phase). Study patients were grouped according to which drug they received, and subgrouped based on whether they received a single or multiple IM injections. Rates of transition to lower (5-10 mg/d) versus higher (15-20 mg/d) dosages were compared within and between treatments.. Data from 236 patients were analyzed (olanzapine, 121 patients [76 men, 45 women; mean (SD) age, 38.4 (12.2) years; mean (SD) weight, 74.9 (18.5) kg]; haloperidol, 115 patients [80 men, 35 women; mean (SD) age, 38.0 (10.2) years; mean (SD) weight, 75.4 (18.7) kg]). At the end of the IM phase, the rate of haloperidol patients who were transitioned to lower oral doses was significantly higher in the single-injection subgroup compared with the multiple-injection subgroup (P = 0.03); this difference was not found in the group receiving olanzapine. At day 4 of oral treatment, the rates of patients in the olanzapine and haloperidol groups who were transitioned to higher oral doses were significantly higher in the single-injection subgroups compared with the multiple-injection subgroups (P = 0.002 and =0.003, respectively).. In this study, the proportion of agitated patients with schizophrenia who transitioned to higher dosages (15-20 mg) of olanzapine or haloperidol by day 4 of the oral switch was significantly greater in patients who were previously treated with a single IM injection of olanzapine (10 mg) or haloperidol (7.5 mg).right.

Topics: Administration, Oral; Adult; Antipsychotic Agents; Benzodiazepines; Female; Haloperidol; Humans; Injections, Intramuscular; Male; Olanzapine; Psychomotor Agitation; Randomized Controlled Trials as Topic; Retrospective Studies; Schizophrenia; Schizophrenic Psychology; Time Factors

Olanzapine is an atypical antipsychotic drug that is increasingly used in intentional drug overdoses. Although acute olanzapine overdose is predominantly associated with anticholinergic symptoms and central nervous system depression, miosis and unpredictable fluctuations between somnolence/coma and agitation/ aggression have been suggested as typical signs of olanzapine intoxication in single case reports.. To confirm the suggestion that fluctuating central nervous system changes and miosis are characteristic signs of olanzapine intoxication. To estimate the dose-response relationship as a guide for the provision of optimal management of olanzapine intoxicated patients.. Retrospective analysis of all well-documented cases of olanzapine intoxication reported to the Swiss Toxicological Information Centre between January 1997 and October 2001. Inclusion criteria for detailed analysis were patient age > or = 16 yr, acute olanzapine monointoxication, ingested dose > 20 mg, and a causal relationship between olanzapine overdose and clinical effects. The Poisoning Severity Score of the European Association of Poison Centres and Clinical Toxicologists (EAPCCT) assessed the intoxication severity.. Out of a total of 131 cases of olanzapine overdose, 26 cases fulfilled the inclusion criteria. The ingested olanzapine doses ranged from 30 to 840 mg. The most frequent findings were somnolence (77%), agitation (42%), and miosis (31%). The Poisoning Severity Score was "minor" in 14 (54%), "moderate" in 11 (42%), and "severe" in 1 (4%) patients. Nine patients (35% of all patients) with moderate olanzapine poisoning (120-840 mg) showed unpredictable fluctuations between somnolence and agitation. Five of these patients also demonstrated marked miosis. All patients recovered within 48h. One patient with severe poisoning (560 mg) had coma and convulsions. Moderate (and severe) symptoms occurred only at ingested doses above 120 mg. There was a statistically significant association between increasing ingested olanzapine doses and poisoning severity.. Although olanzapine is tolerated relatively well in acute overdose, unpredictable and transient fluctuations between central nervous system depression and agitation, frequently associated with miosis, appear to be characteristic findings in moderate to high olanzapine overdoses. They are transient in nature and require careful clinical monitoring but rarely require specific therapeutic interventions.

Topics: Activity Cycles; Adolescent; Adult; Aggression; Antipsychotic Agents; Benzodiazepines; Coma; Disorders of Excessive Somnolence; Drug Overdose; Female; Humans; Male; Middle Aged; Nervous System Diseases; Olanzapine; Psychomotor Agitation; Retrospective Studies; Severity of Illness Index

Olanzapine is an atypical antipsychotic with proven therapeutic effect, though it is rarely used in agitated patients. This study was to assess the effectiveness and safety of a 20-mg initial dose of olanzapine to control agitation of hospitalized patients with schizophrenia and schizoaffective and schizofreniform disorders.. A group of 95 patients aged 18-65 years was observed for 7 days. Effectiveness was assessed according to the CGI and PANSS (including the positive and negative symptoms and excitement subscale PANSS-EC) scales. Adverse events were also recorded.. Two therapeutic groups were distinguished: patients treated with olanzapine alone (OLZ) and those whose condition necessitated at least one administration of benzodiazepines (OLZ + BZ). Although these groups differed with respect to baseline symptom severity, improvement was similar. In the OLZ group, improvement according to the CGI scale was observed after 2 h and persisted to the end of the study. In the OLZ + BZ group there was improvement after 1 h, but not after 2 h. Significant improvement reappeared after 6 h and persisted. Improvement measured by the PANSS-EC scale was noted in the OLZ group after 2 h and in the OLZ + BZ group after 6 h, persisting in both groups from the 12th hr to the end of the observation.. Olanzapine is an antipsychotic which, used alone or in combination with benzodiazepines, is effective and well tolerated in treatment of agitation in schizophrenic patients. Further studies are warranted.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Female; Humans; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Psychomotor Agitation; Psychotic Disorders; Schizophrenia; Time Factors

When only a certain proportion of subjects respond to treatment ('responders') or may never experience an event of interest (thus 'cured'), mixture models often lead to increased understanding of the treatment or disease process. This paper focuses on hypothesis testing in a dose-response framework and shows that increased power is possible by using a mixture model where both the logit of the response rate and the response mean are linear functions of the dose level. Three score tests are developed for testing an overall effect and permutation methods are used to control the type I error. Extensive simulations establish the power properties of the tests and show that our proposed score test has the best performance. The approach is illustrated by a multi-country clinical trial of rapid acting Intramuscular Olanzapine.

Topics: Algorithms; Benzodiazepines; Biometry; Clinical Trials as Topic; Dose-Response Relationship, Drug; Humans; Injections, Intramuscular; Likelihood Functions; Linear Models; Models, Statistical; Monte Carlo Method; Olanzapine; Pharmaceutical Preparations; Psychomotor Agitation; Schizophrenia

Topics: Aged; Aged, 80 and over; Benzodiazepines; Coma; Female; Humans; Hypoglycemia; Olanzapine; Pirenzepine; Psychomotor Agitation; Selective Serotonin Reuptake Inhibitors

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Drug Therapy, Combination; Female; Humans; Intellectual Disability; Male; Olanzapine; Pirenzepine; Psychomotor Agitation; Valproic Acid

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

Neuroleptic malignant syndrome (NMS) is a rare and potentially fatal complication precipitated by the use of antipsychotic medications, most notably haloperidol. Criteria previously described include: exposure to the neuroleptic class of medications; hyperthermia; muscle rigidity; a cluster of laboratory and physical findings that may include mental status changes, autonomic instability, creatine phosphokinase elevation and leukocytosis, and exclusion of other causes for the patient's condition. A prodrome of mental status changes, autonomic instability, tremors, diaphoresis, excess salivation, and extrapyramidal signs may precede NMS. Prior reports of NMS linked to olanzapine have been in patients who had been previously treated with other neuroleptic agents or in patients who had previous episodes of NMS precipitated by other neuroleptics. Several cases included patients treated with olanzapine in addition to another neuroleptic. This report describes a case of NMS associated with olanzapine in a patient who had not previously been exposed to the neuroleptic drug class. At the time this patient presented, there were no reports in the literature of NMS associated with olanzapine alone. Treatment of NMS includes: immediate withdrawal of all neuroleptics; supportive care; fever control; management of autonomic instability (tachycardia, tachypnea, blood pressure fluctuations); and pharmacologic management with dantrolene and bromocriptine.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Female; Humans; Neuroleptic Malignant Syndrome; Olanzapine; Pirenzepine; Psychomotor Agitation

We present the case of a 31-year-old woman with recent refractory bipolar disorder who developed a malignant syndrome preceded by catatonic motor features. This resistant case of lethal catatonia responded selectively to high-dose olanzapine treatment. The case illustrates the need to consider lethal catatonia in apparent cases of neuroleptic malignant syndrome that do not respond to conventional treatment with dantrolene and bromocriptine.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Catatonia; Electroconvulsive Therapy; Female; Humans; Neuroleptic Malignant Syndrome; Olanzapine; Pirenzepine; Psychomotor Agitation

Three-channel actometry was used to study neuroleptic-induced akathisia (NIA), a common and often serious disorder in association of traditional neuroleptic therapy. The aim was to explore the diagnostic possibilities of actometry in NIA and to examine in detail the motor phenomenology of the disorder in detail. The actometers were attached to the ankles and waists of ten patients, suffering from NIA, and to ten matched healthy controls. Five of the patients were changed to olanzapine treatment, and these patients were re-examined during the no-NIA condition. NIA was associated with manyfold movement activity during controlled rest (sitting) but not with increased daily overall motor activity. Movement frequencies in NIA seemed to be pathognomonic. Actometry is promising for investigation and clinical assessment of NIA. Olanzapine proved to be an adequate treatment choice for NIA patients.

Topics: Adult; Akathisia, Drug-Induced; Antipsychotic Agents; Benzodiazepines; Case-Control Studies; Diagnosis, Differential; Female; Humans; Kymography; Male; Middle Aged; Motor Activity; Olanzapine; Pirenzepine; Psychomotor Agitation; Severity of Illness Index