olanzapine and Depressive-Disorder--Major

Antipsychotics are widely used in the treatment of major depressive disorder (MDD), but there has been no comprehensive meta-analytic assessment that examined their use as monotherapy and adjunctive therapy.. A systematic review and a meta-analysis were conducted on randomized placebo-controlled trials (RCTs) that reported on the efficacy and safety/tolerability of antipsychotics for the treatment of adults with MDD. Data of both monotherapy and adjunctive antipsychotic use were extracted, but analyzed separately using a random-effects model. Co-primary outcomes were study-defined-treatment response and intolerability-related discontinuation. We also illustrated the risk/benefit balance of antipsychotics for MDD, using two-dimensional graphs representing the primary efficacy and safety/tolerability outcome. Secondary outcomes included psychopathology, remission, all-cause-discontinuation, inefficacy-related discontinuation, and adverse events.. Forty-five RCTs with 12 724 patients were included in the analysis. In monotherapy (studies = 13,. Results suggest that there are significant differences regarding the risk/benefit ratio among antipsychotics for MDD, which should inform clinical care.

Topics: Adult; Amisulpride; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Dibenzothiazepines; Humans; Olanzapine; Quetiapine Fumarate; Risperidone

Atypical antipsychotic (AAP) augmentation is an alternative strategy for patients with major depressive disorder (MDD) who had an inadequate response to antidepressant therapy (ADT). We aimed to compare and rank the efficacy and safety of 4 AAPs in the adjuvant treatment of MDD.. We searched randomized controlled trials (RCTs) published and unpublished from the date of databases and clinical trial websites inception to April 30, 2023. The evidence risk of bias (RoB) and certainty are assessed using the Cochrane bias risk tool and grading of recommendations assessment, development, and evaluation (GRADE) framework, respectively. Using network meta-analysis, we estimated summary risk ratios (RRs) or standardized mean difference (SMD) based on the random effects model.. 56 eligible studies comprising 11448 participants were included. In terms of primary efficacy outcome, compared with placebo (PBO), all AAPs had significant efficacy (SMD = -0.40; 95% CI, -0.68 to -0.12 for quetiapine (QTP); -0.35, -0.59 to -0.11 for olanzapine (OLA); -0.28, -0.47 to -0.09 for aripiprazole (ARI) and -0.25, -0.42 to -0.07 for brexpiprazole (BRE), respectively). In terms of acceptability, no significant difference was found, either agents versus agents or agents versus PBO. In terms of tolerability, compared with the PBO, QTP (RR = 0.24; 95% CI,0.11-0.53), OLA (0.30,0.10-0.55), ARI (0.39,0.22-0.69), and BRE (0.37,0.18-0.75) were significantly less well tolerated. 8 (14.2%) of 56 trials were assessed as low RoB, 38 (67.9%) trials had moderate RoB, and 10 (17.9%) had high RoB; By the GRADE, the certainty of most evidence was low or very low.. Adjuvant AAPs had significant efficacy compared with PBO, but treatment decisions must be made to balance the risks and benefits.

Topics: Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Adult; Antipsychotic Agents; Aripiprazole; Depressive Disorder, Major; Humans; Network Meta-Analysis; Olanzapine; Quetiapine Fumarate

Pharmacological treatment of major depressive disorder is often inefficient, and multiple strategies are used for inadequate response to antidepressants. Second-generation antipsychotics are used as augmentation measures in clinical practice; evidence of their efficacy and acceptability is insufficient, and it remains confusing as to which drug should be selected first. In this systematic review and network meta-analysis, we included randomised controlled trials of second-generation antipsychotics used as adjunctive treatment in patients with suboptimal responses. Outcome measures were efficacy (response and remission) and acceptability (dropout due to any reason and adverse events). Thirty-three trials comprising 10 602 participants were included. Regarding efficacy, response rates indicated that all antipsychotics except for ziprasidone were more efficacious than the placebo, with the odds ratios (ORs) ranging from 1.34 for olanzapine and cariprazine [95% credible interval (CrI) 1.04-1.73 and 1.07-1.67, respectively] to 2.17 for risperidone (95% CrI 1.38-3.42). When considering remission, cariprazine was not effective (OR 1.21, 95% CrI 0.96-1.54). For acceptability, quetiapine (OR 0.68, 95% CrI 0.50-0.91), brexpiprazole (OR 0.69, 95% CrI 0.55-0.86), and cariprazine (OR 0.61, 95% CrI 0.46-0.82) were worse than the placebo. With regards to tolerability, only olanzapine (OR 0.51, 95% CrI 0.25-1.07) and risperidone (OR 0.48, 95% CrI 0.10-2.21) showed no significant differences compared with placebo. The administration of adjunctive antipsychotics is associated with high effectiveness and low acceptability. Risperidone and aripiprazole are more efficacious and accepted than other atypical antipsychotics.

Topics: Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Depressive Disorder, Major; Humans; Network Meta-Analysis; Olanzapine; Quetiapine Fumarate; Risperidone

This systematic review provided a critical synthesis and a comprehensive overview of guidelines on the treatment of mixed states.. The MEDLINE/PubMed and EMBASE databases were systematically searched from inception to March 21st, 2018. International guidelines covering the treatment of mixed episodes, manic/hypomanic, or depressive episodes with mixed features were considered for inclusion. A methodological quality assessment was conducted with the Appraisal of Guidelines for Research and Evaluation-AGREE II.. The final selection yielded six articles. Despite their heterogeneity, all guidelines agreed in interrupting an antidepressant monotherapy or adding mood-stabilizing medications. Olanzapine seemed to have the best evidence for acute mixed hypo/manic/depressive states and maintenance treatment. Aripiprazole and paliperidone were possible alternatives for acute hypo/manic mixed states. Lurasidone and ziprasidone were useful in acute mixed depression. Valproate was recommended for the prevention of new mixed episodes while lithium and quetiapine in preventing affective episodes of all polarities. Clozapine and electroconvulsive therapy were effective in refractory mixed episodes. The AGREE II overall assessment rate ranged between 42% and 92%, indicating different quality level of included guidelines.. The unmet needs for the mixed symptoms treatment were associated with diagnostic issues and limitations of previous research, particularly for maintenance treatment.

Topics: Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Drug Therapy, Combination; Electroconvulsive Therapy; Humans; Lithium; Lurasidone Hydrochloride; Olanzapine; Paliperidone Palmitate; Piperazines; Practice Guidelines as Topic; Quetiapine Fumarate; Thiazoles; Valproic Acid

We assessed the efficacy and tolerability of the augmentation of antidepressants (ATDs) with atypical antipsychotics (AAPs) to treat patients with major depressive disorder. A retrograde study to identify relevant patient data included databases of PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Database of Abstracts of Reviews of Effects. Data from 17 trials, involving 3807 participants, were identified. The remission rate (RR) and overall response rate (ORR) of adjunctive treatment with AAPs were significantly higher than placebo treatment: RR=1.90 (95%CI=1.61-2.23, z=7.74, P<0.00001) and ORR=1.68 (95%CI=1.45-1.94, z=7.07, P<0.00001). We found that the short-term (4 weeks) treatment [ORR=1.70 (95%CI=0.98-2.95, Z=1.89, P=0.06)] was significantly different from the long-term (6-12 weeks) treatment [ORR=1.68 (95%CI=1.45-1.94, z=7.07, P<0.00001)]. No significant difference in ORR was observed between groups with or without sedative drugs. The discontinuation rate due to adverse effects was higher for adjunctive treatment with AAPs: ORR=3.32 (95%CI=2.35-4.70, z=6.78, P<0.00001). These results demonstrate that the augmentation of ATDs with AAPs (olanzapine, quetiapine, aripiprazole, and risperidone) was more effective than a placebo in improving response and remission rates, although associated with a higher discontinuation rate due to adverse effects.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Chemotherapy, Adjuvant; Depressive Disorder, Major; Dibenzothiazepines; Double-Blind Method; Drug Synergism; Humans; Middle Aged; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Remission Induction; Risperidone; Treatment Outcome; Young Adult

The aim of this systematic review was to examine the efficacy and safety of second-generation antipsychotics (SGAs) in nonpsychotic major depressive disorder (MDD).. In MDD, SGA monotherapy or adjunctive therapy to conventional antidepressants showed rapid onset of antidepressant efficacy. Although maintenance data are limited, quetiapine monotherapy, risperidone adjunctive therapy, and amisulpride adjunctive therapy significantly delayed the time to relapse as compared with placebo. In general, extrapyramidal symptoms appeared to be low with SGAs, but a higher incidence of akathisia was observed with aripiprazole. An elevated risk of weight gain was observed with olanzapine-fluoxetine combination, risperidone, aripiprazole, and quetiapine compared with placebo. At present, there are insufficient data to confidently distinguish between different SGAs in the treatment of MDD. A recent meta-analysis found that adjunctive SGAs were significantly more effective than placebo, but differences in efficacy were not identified among the studied agents, nor were outcomes affected by trial duration or the method of establishing treatment resistance.. Both SGA monotherapy and adjunctive therapy showed greater efficacy in the treatment of MDD than placebo, but augmentation is more widely utilized in treatment-resistant depression. Clinicians should routinely monitor for cardiometabolic side-effects and extrapyramidal symptoms during SGA therapy.

Topics: Adult; Amisulpride; Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Depressive Disorder, Major; Dibenzothiazepines; Drug Therapy, Combination; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Sulpiride

Olanzapine/fluoxetine (Symbyax) is an oral, once-daily, fixed-dose combination of the atypical antipsychotic olanzapine and the selective serotonin reuptake inhibitor (SSRI) fluoxetine. It is indicated, in adult patients, for the acute treatment of depressive episodes associated with bipolar I disorder and treatment-resistant major depressive disorder. In adult patients with treatment-resistant depression (major depressive disorder in adults who do not respond to two separate trials of different antidepressants of adequate dose and duration in the current episode), olanzapine plus fluoxetine combination therapy was generally more effective than either drug as monotherapy based on an integrated analysis of clinical trials of 8-12 weeks' duration. More limited data also indicate that longer-term treatment for 76 weeks with olanzapine plus fluoxetine was efficacious in this patient group. Combination therapy was generally well tolerated, with a tolerability profile similar to that of olanzapine monotherapy, although fluoxetine monotherapy was generally better tolerated than olanzapine plus fluoxetine. The combination of olanzapine plus fluoxetine, as a fixed-dose formulation, offers a useful treatment option in this difficult-to-treat patient group.

Topics: Benzodiazepines; Clinical Trials as Topic; Databases, Factual; Depressive Disorder, Major; Fluoxetine; Humans; Olanzapine; Selective Serotonin Reuptake Inhibitors; Time Factors

To describe the efficacy and safety of adjunctive aripiprazole, olanzapine, and quetiapine for major depressive disorder.. Published registration study reports, supplemented by clinical trial synopses as disclosed by manufacturers and product labeling.. All available reports of studies were identified.. Descriptions of the principal results and calculation of number needed to treat (NNT) for response and remission and number needed to harm (NNH) for relevant dichotomous adverse outcomes were extracted. Likelihood to be helped or harmed (LHH) was subsequently calculated.. Three registration studies of adjunctive aripiprazole, 5 for olanzapine-fluoxetine combination, and 2 for quetiapine extended-release reveal NNT for response and remission to range from 7 to 14 and 7 to 13, respectively, for adjunctive antipsychotic versus antidepressant monotherapy, depending on the antipsychotic and/or dose. Adverse event profiles for the 3 different adjunctive antipsychotics are more diverse, with adjunctive aripiprazole more strongly associated with akathisia (NNH, 6), adjunctive olanzapine with weight gain (NNH, 3), and adjunctive quetiapine with somnolence (NNH, 5 for 300 mg/d and NNH, 6 for 150 mg/d).. Number needed to treat and NNH can be used to quantify efficacy and tolerability outcomes and help place various therapeutic options into clinical perspective. Likelihood to be helped or harmed can illustrate to the clinician and the patient the trade-offs between obtaining potential benefits versus harms. In the case of the adjunctive second-generation antipsychotics approved for treating major depressive disorder, these trade-offs vary greatly among the choices available and require careful, individualized, patient-centered clinical decision making.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Biostatistics; Clinical Trials as Topic; Depressive Disorder, Major; Dibenzothiazepines; Drug Combinations; Drug Therapy, Combination; Epidemiologic Measurements; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones

Major depressive disorder (MDD) is a common condition with a lifetime prevalence of 15% to 18%, which leads to considerable suffering and disability. Some antipsychotics have been reported to induce remission in major depression, when added to an antidepressant.. To evaluate the effects of second-generation antipsychotic (SGA) drugs (alone or augmentation) compared with placebo or antidepressants for people with MDD or dysthymia.. The Cochrane Depression, Anxiety and Neurosis Group's controlled trial registers (CCDANCTR-Studies and CCDANCTR-References) were searched up to 21 July 2010. The author team ran complementary searches on clinicaltrials.gov and contacted key authors and drug companies.. We included all randomised, double-blind trials comparing oral SGA treatment (alone or augmentation) with other forms of pharmaceutical treatment or placebo in people with MDD or dysthymia.. We extracted data independently. For dichotomous data we calculated the odds ratio (OR) and 95% confidence interval (CI) on an intention-to-treat basis, and for continuous data the mean difference (MD), based on a random-effects model. We presented each comparison separately; we did not perform a pooled data analysis.. We included 28 trials with 8487 participants on five SGAs: amisulpride, aripiprazole, olanzapine, quetiapine and risperidone.Three studies (1092 participants) provided data on aripiprazole augmentation in MDD. All efficacy data (response n = 1092, three RCTs, OR 0.48; 95% CI 0.37 to 0.63), (MADRS n = 1077, three RCTs, MD -3.04; 95% CI -4.09 to -2) indicated a benefit for aripiprazole but  more side effects (weight gain, EPS) .Seven trials (1754 participants) reported data on olanzapine. Compared to placebo fewer people discontinued treatment due to inefficacy; compared to antidepressants there were no efficacy differences, olanzapine augmentation showed symptom reduction (MADRS n = 808, five RCTs, MD -2.84; 95% CI -5.48 to -0.20), but also more weight or prolactin increase.Quetiapine data are based on seven trials (3414 participants). Compared to placebo, quetiapine monotherapy (response n = 1342, three RCTs, OR 0.52; 95% CI 0.41 to 0.66) and quetiapine augmentation (response n = 937, two RCTs, OR 0.68; 95% CI 0.52 to 0.90) showed symptom reduction, but quetiapine induced more sedation.Four trials (637 participants) presented data on risperidone augmentation, response data were better for risperidone (n = 371, two RCTs, OR 0.57; 95% CI 0.36 to 0.89) but augmentation showed more prolactin increase and weight gain.Five studies (1313 participants) presented data on amisulpride treatment for dysthymia. There were some beneficial effects compared to placebo or antidepressants but tolerability was worse.. Quetiapine was more effective than placebo treatment. Aripiprazole and quetiapine and partly also olanzapine and risperidone augmentation showed beneficial effects compared to placebo. Some evidence indicated beneficial effects of low-dose amisulpride for dysthymic people. Most SGAs showed worse tolerability.

Topics: Amisulpride; Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Depressive Disorder, Major; Dibenzothiazepines; Dysthymic Disorder; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risperidone; Sulpiride

There has been growing evidence supporting the use of atypical antipsychotic drugs as adjunctive treatments in patients with major depression who fail to respond adequately to antidepressants.. To review the efficacy and safety data for one such combination, fluoxetine (FLX) + olanzapine (OLZ) in treatment-resistant depression (TRD).. We reviewed published randomized, controlled acute-phase studies, as well as available long-term clinical studies.. In each acute-phase study (n = 5), FLX/OLZ group experienced rapid antidepressant effects and, in two of these studies, resulted in significantly greater improvement at study end point compared with antidepressant monotherapy. These effects were strongest when TRD was defined as having failed at least two antidepressant trials during the current depressive episode. FLX + OLZ was generally well tolerated; however, increases in body weight and prolactin levels with FLX + OLZ were greater than that of antidepressant monotherapy groups and were similar to OLZ monotherapy. However, changes in random total cholesterol were also greatest for FLX + OLZ and were greater in magnitude than that of OLZ or FLX monotherapy. Long-term effectiveness/safety data are sparse, and comparison trials and sequential treatment studies involving FLX + OLZ and other antidepressant-atypical antipsychotic combinations are lacking. Thus, the exact place of FLX + OLZ among other available options for TRD is difficult to determine.

Topics: Antidepressive Agents, Second-Generation; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Drug Therapy, Combination; Female; Fluoxetine; Humans; Male; Olanzapine; Randomized Controlled Trials as Topic; Treatment Outcome

Psychogenic tremor is a variant of psychogenic movement disorder. Psychogenic tremor often starts in an abrupt manner and affects voluntary motor function, rapidly reaching maximum impairment for the patient. Patients often present with comorbid psychiatric disorders, including depression, anxiety and personality disorders. Overall prognosis is poor, with 80 to 90 percent of patients symptomatic after one year. The authors present the case of a 33-year-old woman who experienced an acute episode of psychogenic tremor. They review the literature on psychiatric and neurologic manifestations of psychogenic tremor, consider diagnostic and treatment implications and discuss overall prognosis of recovery for patients afflicted with psychogenic tremor.

Topics: Adult; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Cognitive Behavioral Therapy; Depressive Disorder, Major; Drug Therapy, Combination; Duloxetine Hydrochloride; Female; Hospitalization; Humans; Olanzapine; Psychophysiologic Disorders; Thiophenes; Tremor

Atypical antipsychotics (AAPs) have been hypothesized to be beneficial in treatment-resistant depression (TRD). This paper will review a biochemical rationale and will summarize the data regarding the effectiveness of AAPs in TRD.. Studies were identified using searches of Pubmed/Medline, EMBase and the Cochrane databases by cross-referencing the term 'depression' with each of the six AAPs.. After initial positive, short case reports and clinical trials, larger studies failed to show the effectiveness of AAPs combined with antidepressants for TRD. More recently, larger scale clinical trials have supported the effectiveness of at least some of these medications. While AAPs have gained in popularity for TRD, there are nagging concerns regarding risks such as metabolic syndrome and tardive dyskinesia.. The existing research provides some support for the beneficial effects of AAPs when combined with SSRI's in TRD. These medications pose significant risks that must be considered in their use.

Topics: Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Depressive Disorder, Major; Dibenzothiazepines; Dopamine D2 Receptor Antagonists; Drug Resistance; Drug Therapy, Combination; Fluoxetine; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Serotonin 5-HT2 Receptor Antagonists; Thiazoles; Trazodone; Triazoles

Studies have found that a large percentage of depressed patients may have limited response and remission rates when treated with traditional antidepressants. Options for augmenting antidepressant treatment include buspirone, lithium, and triiodothyronine. There are also increasing data concerning the use of atypical antipsychotics as augmenting agents in the treatment of unipolar, nonpsychotic, treatment-resistant depression. Aripiprazole has recently received an indication from the U.S. Food and Drug Administration (FDA) for adjunctive treatment in unipolar, nonpsychotic depression, the first indication of its kind, after two double-blind trials; doses were slightly lower than those recommended for monotherapy in schizophrenia or bipolar disorder. Olanzapine and risperidone have several controlled clinical trials indicating the efficacy of both of these agents, generally at low doses. One trial of quetiapine suggested that it may not be effective in the treatment of unipolar, nonpsychotic depression. One open-label trial of ziprasidone indicated some efficacy. According to these results, aripiprazole, olanzapine, and risperidone are reasonable choices as augmentation agents, with only aripiprazole currently having an FDA indication for this use. Given the preliminary results, double-blind, placebo-controlled trials with quetiapine and ziprasidone are needed, as well as studies comparing atypical antipsychotic agents with traditional augmentation agents in the treatment of depression.

Topics: Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Clozapine; Depressive Disorder, Major; Dibenzothiazepines; Drug Synergism; Drug Therapy, Combination; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Risperidone; Thiazoles

Atypical antipsychotics are increasingly used for treatment of mental illnesses like schizophrenia and bipolar disorder, and considered to have fewer extrapyramidal effects than older antipsychotics.. We examined efficacy in randomised trials of bipolar disorder where the presenting episode was either depression, or manic/mixed, comparing atypical antipsychotic with placebo or active comparator, examined withdrawals for any cause, or due to lack of efficacy or adverse events, and combined all phases for adverse event analysis. Studies were found through systematic search (PubMed, EMBASE, Cochrane Library), and data combined for analysis where there was clinical homogeneity, with a special reference to trial duration.. In five trials (2,206 patients) participants presented with a depressive episode, and in 25 trials (6,174 patients) the presenting episode was manic or mixed. In 8-week studies presenting with depression, quetiapine and olanzapine produced significantly better rates of response and symptomatic remission than placebo, with NNTs of 5-6, but more adverse event withdrawals (NNH 12). With mania or mixed presentation atypical antipsychotics produced significantly better rates of response and symptomatic remission than placebo, with NNTs of about 5 up to six weeks, and 4 at 6-12 weeks, but more adverse event withdrawals (NNH of about 22) in studies of 6-12 weeks. In comparisons with established treatments, atypical antipsychotics had similar efficacy, but significantly fewer adverse event withdrawals (NNT to prevent one withdrawal about 10). In maintenance trials atypical antipsychotics had significantly fewer relapses to depression or mania than placebo or active comparator. In placebo-controlled trials, atypical antipsychotics were associated with higher rates of weight gain of >or=7% (mainly olanzapine trials), somnolence, and extrapyramidal symptoms. In active controlled trials, atypical antipsychotics were associated with lower rates of extrapyramidal symptoms, but higher rates of weight gain and somnolence.. Atypical antipsychotics are effective in treating both phases of bipolar disorder compared with placebo, and as effective as established drug therapies. Atypical antipsychotics produce fewer extrapyramidal symptoms, but weight gain is more common (with olanzapine). There is insufficient data confidently to distinguish between different atypical antipsychotics.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Bipolar Disorder; Depressive Disorder, Major; Dibenzothiazepines; Humans; Lamotrigine; Olanzapine; Prevalence; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Surveys and Questionnaires; Treatment Outcome; Triazines

Antidepressant medications have eased the suffering of millions of people. In addition to treating depression, antidepressant drugs also treat several anxiety disorders. Unfortunately, there are problematic limitations with antidepressant agents, including a delayed therapeutic response and insufficient efficacy. Emerging evidence shows that atypical antipsychotic agents can be used as augmentation therapy in patients with poor responses to antidepressants. Future drugs combining key features of antidepressant and atypical antipsychotic agents could offer new promise for patients suffering from obsessive-compulsive disorder, post-traumatic stress disorder, panic disorder, generalized anxiety disorder and depression.

Topics: Animals; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Depressive Disorder, Major; Dibenzothiazepines; Drug Design; Drug Synergism; Drug Therapy, Combination; Humans; Obsessive-Compulsive Disorder; Olanzapine; Quetiapine Fumarate; Receptors, Dopamine; Receptors, Histamine; Receptors, Serotonin; Risperidone; Stress Disorders, Post-Traumatic

Atypical antipsychotics are widely used in clinical practice for several psychiatric disorders. Between 1994 and 1999, 26 cases of manic and hypomanic syndromes were reported with olanzapine and risperidone and were described in a previous review article.. An updated MEDLINE search (1999-2003) using the terms atypical antipsychotics, amisulpride, aripiprazole, clozapine, flupenthixol, olanzapine, quetiapine, risperidone, sertindole, ziprasidone, zotepine, hypomania, and mania showed that 34 new cases of induced hypomanic or manic syndromes have been published, not only with olanzapine (N = 5) and risperidone (N = 6), but also with quetiapine (N = 5) and ziprasidone (N = 11) treatment. Six cases have been reported with flupenthixol and 1 with amisulpride, two antipsychotics considered as "partial" atypicals.. A critical analysis of these case reports revealed that the effects on mood were insufficiently documented in some of the reports but that for 20 of them, evidence is highly suggestive of a causative role of atypical antipsychotics in the induction of manic/hypomanic symptomatology.. This updated review continues and extends the results of the initial review and suggests that atypical antipsychotics have some intriguing effects on mood. Such effects have never been reported with conventional antipsychotics. The mechanisms involved in this phenomenon of mood switch remain to be elucidated.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder, Major; Female; Humans; Male; Middle Aged; Olanzapine; Practice Guidelines as Topic; Practice Patterns, Physicians'; Psychotic Disorders; Risperidone; Schizophrenia

Cumulative data indicate that atypical antipsychotics can serve as adjunctive as well as alternative agents in the treatment of drug-resistant mood disorders. Olanzapine and risperidone add-on treatment was found to be effective for major depression with psychotic features and good results were achieved with currently available atypical antipsychotics (clozapine, risperidone, olanzapine, quetiapine and ziprasidone) in reducing symptoms of acute mania, especially when added to mood stabilizers. The role of atypical antipsychotics in maintenance and prophylactic treatment is not yet clear. Although there are differences in the side effect profiles of the various atypical antipsychotics, their use is limited by adverse effects such as extrapyramidal symptoms, weight gain, somnolence and sexual dysfunction.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Clozapine; Depressive Disorder, Major; Dibenzothiazepines; Humans; Olanzapine; Piperazines; Pirenzepine; Quetiapine Fumarate; Risperidone; Thiazoles

The effect of antipsychotic medication on resting state functional connectivity in major depressive disorder (MDD) is currently unknown. To address this gap, we examined patients with MDD with psychotic features (MDDPsy) participating in the Study of the Pharmacotherapy of Psychotic Depression II. All participants were treated with sertraline plus olanzapine and were subsequently randomized to continue sertraline plus olanzapine or be switched to sertraline plus placebo. Participants completed an MRI at randomization and at study endpoint (study completion at Week 36, relapse, or early termination). The primary outcome was change in functional connectivity measured within and between specified networks and the rest of the brain. The secondary outcome was change in network topology measured by graph metrics. Eighty-eight participants completed a baseline scan; 73 completed a follow-up scan, of which 58 were usable for analyses. There was a significant treatment X time interaction for functional connectivity between the secondary visual network and rest of the brain (t = -3.684; p = 0.0004; pFDR = 0.0111). There was no significant treatment X time interaction for graph metrics. Overall, functional connectivity between the secondary visual network and the rest of the brain did not change in participants who stayed on olanzapine but decreased in those switched to placebo. There were no differences in changes in network topology measures when patients stayed on olanzapine or switched to placebo. This suggests that olanzapine may stabilize functional connectivity, particularly between the secondary visual network and the rest of the brain.

Topics: Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Drug Therapy, Combination; Humans; Magnetic Resonance Imaging; Olanzapine; Sertraline

Prescriptions for antipsychotic medications continue to increase across many brain disorders, including off-label use in children and elderly individuals. Concerning animal and uncontrolled human data suggest antipsychotics are associated with change in brain structure, but to our knowledge, there are no controlled human studies that have yet addressed this question.. To assess the effects of antipsychotics on brain structure in humans.. Prespecified secondary analysis of a double-blind, randomized, placebo-controlled trial over a 36-week period at 5 academic centers. All participants, aged 18 to 85 years, were recruited from the multicenter Study of the Pharmacotherapy of Psychotic Depression II (STOP-PD II). All participants had major depressive disorder with psychotic features (psychotic depression) and were prescribed olanzapine and sertraline for a period of 12 to 20 weeks, which included 8 weeks of remission of psychosis and remission/near remission of depression. Participants were then were randomized to continue receiving this regimen or to be switched to placebo and sertraline for a subsequent 36-week period. Data were analyzed between October 2018 and February 2019.. Those who consented to the imaging study completed a magnetic resonance imaging (MRI) scan at the time of randomization and a second MRI scan at the end of the 36-week period or at time of relapse.. The primary outcome measure was cortical thickness in gray matter and the secondary outcome measure was microstructural integrity of white matter.. Eighty-eight participants (age range, 18-85 years) completed a baseline scan; 75 completed a follow-up scan, of which 72 (32 men and 40 women) were useable for final analyses. There was a significant treatment-group by time interaction in cortical thickness (left, t = 3.3; P = .001; right, t = 3.6; P < .001) but not surface area. No significant interaction was found for fractional anisotropy, but one for mean diffusivity of the white matter skeleton was present (t = -2.6, P = .01). When the analysis was restricted to those who sustained remission, exposure to olanzapine compared with placebo was associated with significant decreases in cortical thickness in the left hemisphere (β [SE], 0.04 [0.009]; t34.4 = 4.7; P <.001), and the right hemisphere (β [SE], 0.03 [0.009]; t35.1 = 3.6; P <.001). Post hoc analyses showed that those who relapsed receiving placebo experienced decreases in cortical thickness compared with those who sustained remission.. In this secondary analysis of a randomized clinical trial, antipsychotic medication was shown to change brain structure. This information is important for prescribing in psychiatric conditions where alternatives are present. However, adverse effects of relapse on brain structure support antipsychotic treatment during active illness.. ClinicalTrials.gov Identifier: NCT01427608.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Cerebral Cortex; Depressive Disorder, Major; Diffusion Tensor Imaging; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Middle Aged; Olanzapine; Outcome Assessment, Health Care; Psychotic Disorders; Sertraline; White Matter; Young Adult

Psychotic depression is a severely disabling and potentially lethal disorder. Little is known about the efficacy and tolerability of continuing antipsychotic medication for patients with psychotic depression in remission.. To determine the clinical effects of continuing antipsychotic medication once an episode of psychotic depression has responded to combination treatment with an antidepressant and antipsychotic agent.. Thirty-six week randomized clinical trial conducted at 4 academic medical centers. Patients aged 18 years or older had an episode of psychotic depression acutely treated with sertraline plus olanzapine for up to 12 weeks and met criteria for remission of psychosis and remission or near-remission of depressive symptoms for 8 weeks before entering the clinical trial. The study was conducted from November 2011 to June 2017, and the final date of follow-up was June 13, 2017.. Participants were randomized either to continue olanzapine (n = 64) or switch from olanzapine to placebo (n = 62). All participants continued sertraline.. The primary outcome was risk of relapse. Main secondary outcomes were change in weight, waist circumference, lipids, serum glucose, and hemoglobin A1c (HbA1c).. Among 126 participants who were randomized (mean [SD] age, 55.3 years [14.9 years]; 78 women [61.9%]), 114 (90.5%) completed the trial. At the time of randomization, the median dosage of sertraline was 150 mg/d (interquartile range [IQR], 150-200 mg/d) and the median dosage of olanzapine was 15 mg/d (IQR, 10-20 mg/d). Thirteen participants (20.3%) randomized to olanzapine and 34 (54.8%) to placebo experienced a relapse (hazard ratio, 0.25; 95% CI, 0.13 to 0.48; P < .001). The effect of olanzapine on the daily rate of anthropometric and metabolic measures significantly differed from placebo for weight (0.13 lb; 95% CI, 0.11 to 0.15), waist circumference (0.009 inches; 95% CI, 0.004 to 0.014), and total cholesterol (0.29 mg/dL; 95% CI, 0.13 to 0.45) but was not significantly different for low-density lipoprotein cholesterol (0.04 mg/dL; 95% CI, -0.01 to 0.10), high-density lipoprotein cholesterol (-0.01 mg/dL; 95% CI, -0.03 to 0.01), triglyceride (-0.153 mg/dL; 95% CI, -0.306 to 0.004), glucose (-0.02 mg/dL; 95% CI, -0.12 to 0.08), or HbA1c levels (-0.0002 mg/dL; 95% CI, -0.0021 to 0.0016).. Among patients with psychotic depression in remission, continuing sertraline plus olanzapine compared with sertraline plus placebo reduced the risk of relapse over 36 weeks. This benefit needs to be balanced against potential adverse effects of olanzapine, including weight gain.. ClinicalTrials.gov Identifier: NCT01427608.

Topics: Adolescent; Adult; Affective Disorders, Psychotic; Aged; Antidepressive Agents; Antipsychotic Agents; Depressive Disorder, Major; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Olanzapine; Proportional Hazards Models; Secondary Prevention; Sertraline; Young Adult

Both venlafaxine and olanzapine have been previously found to have anxiolytic properties, however no study examined the effect of their combination on anxiety in anxious MDD. The aim of this study was to reveal if and when venlafaxine/olanzapine combination (VOC) can reduce the anxiety and depressive symptoms in patients with severe MDD at the level of patients with moderate-severe depression treated with venlafaxine monotherapy.. Fifty seven patients were included into the study. Symptoms of depression were objectively assessed by Montgomery-Asberg Depression Rating Scale and subjectively scored by BECK Depression scale, symptoms of anxiety were objectively assessed by Hamilton Anxiety scale and subjectively evluated by ZUNG Self-Rating Anxiety scale before treatment and after each following week untill the fourth week of treatment.. VOC eliminated the pre-treatment score differences in all the scales within the first week of treatment. At the third week, VOC group had significantly lower level of anxiety symptoms and the effect maintained through the fourth week of medication.. Our results indicate that VOC could replace another anxiolytic medication in managing the symptoms of anxiety in patients with severe anxious MDD already within the first week of treatment.

Topics: Adolescent; Adult; Aged; Anti-Anxiety Agents; Anxiety Disorders; Benzodiazepines; Depressive Disorder, Major; Drug Combinations; Female; Humans; Male; Middle Aged; Olanzapine; Severity of Illness Index; Venlafaxine Hydrochloride; Young Adult

To characterize cognitive function at baseline and investigate the relationship between change in cognition, depression, and psychosis after treatment among older adults with major depressive disorder with psychotic features.. This was a secondary analysis of a double-blind, randomized, controlled treatment trial at inpatient and outpatient settings at four academic health centers on "Young Old" (aged 60-71 years, N = 71) and "Older" (aged 72-86 years, N = 71) participants diagnosed with psychotic depression. Olanzapine plus sertraline or olanzapine plus placebo were given until week 12 or termination.. At baseline, Young Old and Older participants did not differ on measures of depression severity or global cognition, information processing speed, and executive function. Improvement in depressive and psychotic symptoms from baseline to treatment end was similar in both the Young Old and Older groups. However, improvement in depressive symptoms was significantly associated with improvement in global cognitive function in Young Old participants but not in Older participants.. Cognitive dysfunction was not a detriment to improvement in symptoms of psychotic major depression in our geriatric patients. Young Old and Older patients improved to a similar degree on measures of depression and delusions from baseline to treatment end. However, improvement in cognition over the course of treatment was more prominent in the Young Old group than in the Older group.

Topics: Aged; Aged, 80 and over; Aging; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Cognition; Depressive Disorder, Major; Double-Blind Method; Drug Therapy, Combination; Humans; Late Onset Disorders; Middle Aged; Olanzapine; Psychotic Disorders; Sertraline; Treatment Outcome

Although depressive symptoms are a frequently occurring phenomenon in schizophrenia, effective treatments remain an area of clinical need.. To assess the benefit of short-term treatment with the atypical antipsychotic asenapine versus placebo on depressive symptoms in patients with acute schizophrenia in an exacerbated state.. Data were pooled from intent-to-treat (ITT) populations of three 6-week, randomized controlled studies with fixed doses of asenapine (ASE; n=427), olanzapine (OLA; n=82), risperidone (RIS; n=54), haloperidol (HAL; n=97), or placebo (PLA; n=254). Change from baseline Calgary Depression Scale for Schizophrenia (CDSS) total score and individual item scores were assessed at Day 21 and Day 42 in the total patient population (n=914), and in patients presenting with a CDSS total score of .6 at baseline (n=248). Mixed model repeated measures (MMRM) analyses were performed on patient data.. The observed change from baseline in CDSS total score was significantly larger with ASE.compared to PLA.at both Day 21 (p<0.05) and Day 42 (p<0.01) for the total patient population group, and at Day 21 (p<0.05) in patients with baseline CDSS total score .6. For both populations, there was a significant change from baseline in the CDSS depression item score with ASE.compared to PLA.at Day 21 (p<0.01, all patient population; p<0.05, patients with baseline CDSS .6), and at Day 42 (p<0.01) in the all patient population. Statistically significant changes from baseline, in favor of ASE versus PLA, were also observed in other individual CDSS item scores including hopelessness (p<0.05, Day 21, patients with baseline CDSS .6), self-depreciation (p<0.05, Day 42, all patient population), guilty ideas of reference (p<0.01, Day 42, all patient population), pathological guilt (p<0.01, Day 21, all patient population; p<0.05, Day 21 and Day 42, patients with baseline CDSS score .6), and observed depression (p<0.05, Day 21, all patient population).. ASE significantly improved a range of depressive symptoms in people with an acute exacerbation of schizophrenia, as measured by the CDSS. ASE may represent a beneficial treatment option for the management of depressive symptoms in patients with schizophrenia.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Dibenzocycloheptenes; Double-Blind Method; Female; Haloperidol; Heterocyclic Compounds, 4 or More Rings; Humans; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome; Young Adult

The comparative antidepressant effects of clozapine and other atypical antipsychotics for schizophrenia remain elusive, leading us to examine this question using the data from the Clinical Antipsychotic Trials of Intervention Effectiveness phase 2E.. Ninety-nine patients who discontinued treatment with olanzapine, quetiapine, risperidone, or ziprasidone because of inadequate efficacy were randomly assigned to open-label treatment with clozapine (n=49) or double-blind treatment with another atypical antipsychotic not previously received in the trial (olanzapine [n=19], quetiapine [n=15], or risperidone [n=16]). The primary outcome was the Calgary Depression Scale for Schizophrenia (CDSS) total score. Antidepressant effects of clozapine and the other atypical antipsychotics were compared in patients with chronic schizophrenia and those with a major depressive episode (MDE) at baseline (i.e. ≥6 on the CDSS), using mixed models.. No differences in the baseline CDSS total scores were found between the treatment groups regardless of presence of an MDE. Clozapine was more effective than quetiapine in antidepressant effects for chronic schizophrenia (p<.01 for the whole sample and p=.01 for those with an MDE), and comparable to olanzapine and risperidone.. The present findings suggest that clozapine demonstrates superior antidepressant effects to quetiapine and comparable effects to olanzapine and risperidone in chronic schizophrenia regardless of presence of MDE. Given the indication of clozapine for treatment-resistant schizophrenia (TRS) and the negative impacts of depressive symptoms on clinical outcomes in schizophrenia, further research is warranted to investigate antidepressant effects of clozapine in TRS with an MDE.

Topics: Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Chronic Disease; Clozapine; Depressive Disorder, Major; Double-Blind Method; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Thiazoles; Treatment Outcome

Clinical evidence and expert opinion support using a combination of an antipsychotic and an antidepressant when treating major depression with psychotic features. We characterized the impact of sertraline co-administration on olanzapine clearance in psychotic depression using population pharmacokinetic methods.. The Study of Pharmacotherapy for Psychotic Depression (STOP-PD) randomized 259 participants to olanzapine plus placebo or olanzapine plus sertraline. Olanzapine was started at 2.5-5 mg/day and sertraline at 25-50 mg/day. Doses were increased to a maximum of 20 mg/day for olanzapine and 200 mg/day for sertraline. Up to four olanzapine concentration samples were collected during the 12-week trial and 12-week continuation phase. We used NONMEM (Version VII) for population pharmacokinetic analysis, assessing effects of the covariates sex, African American origin, smoking, age, and sertraline co-administration.. Population pharmacokinetic analysis comprised 336 samples from 175 individuals. The structural model published by Bigos et al. was sufficient to describe the olanzapine data adequately: a one-compartment model with first-order absorption and elimination, using an additive residual error structure with the absorption rate constant fixed to 0.5. Sertraline co-administration significantly increased olanzapine apparent clearance (p < 0.005) by 25-35 % depending on the patient characteristics included. Male sex was associated with a significantly increased clearance. Age and race did not have a significant impact on clearance.. Contrary to expectations from the knowledge of cytochrome P450 interactions, sertraline increased olanzapine apparent clearance. Plausible explanations include patients treated with sertraline having poorer adherence to olanzapine, or the impact of sertraline inhibition of transporters resulting in increased intracellular concentrations and thus access to metabolizing enzymes.

Topics: Adult; Aged; Benzodiazepines; Depressive Disorder, Major; Drug Interactions; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Models, Biological; Olanzapine; Psychotic Disorders; Sertraline; Sex Factors

To examine whether cerebrovascular risk, executive function, and processing speed are associated with acute treatment outcome of psychotic depression in older adults.. The authors analyzed data from 142 persons aged 60 years or older with major depression with psychotic features who participated in a 12-week randomized controlled trial (RCT) comparing olanzapine plus sertraline with olanzapine plus placebo. The independent variables were baseline cerebrovascular risk (Framingham Stroke Risk Score), baseline executive function (Stroop interference score and the initiation/perseveration subscale of the Mattis Dementia Rating Scale), and baseline processing speed (color and word reading components of the Stroop). The outcome variable was change in severity of depression, measured by the 17-item Hamilton Depression Rating Scale total score, during the course of the RCT.. Greater baseline cerebrovascular risk was significantly associated with less improvement in depression severity over time, after controlling for pertinent covariates. Neither executive function nor processing speed predicted outcome.. This study suggests an association of cerebrovascular risk, but not executive function or processing speed, with treatment outcome of major depression with psychotic features in older adults.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Cerebrovascular Disorders; Cognition; Cognition Disorders; Depressive Disorder, Major; Double-Blind Method; Executive Function; Humans; Mental Processes; Middle Aged; Neuropsychological Tests; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Reaction Time; Risk; Sertraline; Severity of Illness Index; Stroop Test; Treatment Outcome; Young Adult

Observational studies report that selective serotonin reuptake inhibitor (SSRI) antidepressants are associated with an increased risk of falls in the elderly, but these studies may overestimate drug-specific risk because of confounding. A randomized controlled trial (RCT) is the optimal way to assess the causal relationship between use of an SSRI and falls. We therefore analyzed data from a RCT of the treatment of psychotic depression, to examine whether combined olanzapine and sertraline interacted with older age to increase the risk of falling compared with olanzapine plus placebo.. Double-blind placebo-controlled RCT.. Four academic medical centers.. Two hundred fifty-nine patients with major depressive disorder with psychotic features (N = 117 aged 18-59 years and N = 142 aged 60 years or older).. Twelve weeks of randomized double-blind treatment with olanzapine plus sertraline or olanzapine plus placebo.. Proportion of participants who fell at least once.. Older participants were significantly more likely than younger participants to fall. Among older participants, the odds ratio of falling with olanzapine plus sertraline versus olanzapine plus placebo was 1.56 (95% confidence interval: 0.63-3.83). There was not a statistically significant treatment effect or treatment × age interaction with respect to the proportion of participants falling. These negative results may have been due to low statistical power.. Evaluating the association between SSRIs and falls in a RCT is limited by the large sample size that is required. An alternative approach is to examine the effect of an SSRI on measures of postural stability and gait that are valid markers of risk of falling.

Topics: Accidental Falls; Adolescent; Adult; Aged; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Olanzapine; Sertraline; Young Adult

There is no established psychometric instrument dedicated to the measurement of severity in psychotic depression (PD). The aim of this study was to investigate whether a new composite rating scale, the Psychotic Depression Assessment Scale (PDAS), covering both the psychotic and the depressive domains of PD, could detect differences in effect between two psychopharmacological treatment regimens.. We reanalyzed the data from the Study of Pharmacotherapy of Psychotic Depression (STOP-PD), which compared the effect of Olanzapine+Sertraline (n=129) versus Olanzapine+Placebo (n=130). The response to the two regimens was compared using both a mixed effects model and effect size statistics on the total scores of three rating scales: the 17-item Hamilton Depression Rating Scale (HAM-D17), its 6-item melancholia subscale (HAM-D6), and the 11-item PDAS consisting of the HAM-D6 plus five items from the Brief Psychiatric Rating Scale covering psychotic symptoms.. According to both statistical approaches, the PDAS, the HAM-D17 and the HAM-D6 were all able to detect significant differences in treatment effect between Olanzapine+Sertraline and Olanzapine+Placebo (Olanzapine+Sertraline being superior). Notably, 45% of the trial participants were at least "probable psychotic" at their last assessment in the trial.. The STOP-PD was not designed specifically to answer the research questions of the present study.. The Psychotic Depression Assessment Scale (PDAS) is a sensitive measure of treatment response in PD. The fact that 45% of the patients still experienced psychotic symptoms at their last trial assessment emphasizes the need to include items pertaining to psychotic symptoms in rating scales for PD.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Drug Therapy, Combination; Female; Humans; Hypoglycemic Agents; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Sertraline; Treatment Outcome

There are conflicting results on the impact of anxiety on depression outcomes. The impact of anxiety has not been studied in major depression with psychotic features ("psychotic depression").. We assessed the impact of specific anxiety symptoms and disorders on the outcomes of psychotic depression.. We analyzed data from the Study of Pharmacotherapy for Psychotic Depression that randomized 259 younger and older participants to either olanzapine plus placebo or olanzapine plus sertraline. We assessed the impact of specific anxiety symptoms from the Brief Psychiatric Rating Scale ("tension", "anxiety" and "somatic concerns" and a composite anxiety score) and diagnoses (panic disorder and GAD) on psychotic depression outcomes using linear or logistic regression. Age, gender, education and benzodiazepine use (at baseline and end) were included as covariates.. Anxiety symptoms at baseline and anxiety disorder diagnoses differentially impacted outcomes. On adjusted linear regression there was an association between improvement in depressive symptoms and both baseline "tension" (coefficient=0.784; 95% CI: 0.169-1.400; p=0.013) and the composite anxiety score (regression coefficient = 0.348; 95% CI: 0.064-0.632; p=0.017). There was an interaction between "tension" and treatment group, with better responses in those randomized to combination treatment if they had high baseline anxiety scores (coefficient=1.309; 95% CI: 0.105-2.514; p=0.033). In contrast, panic disorder was associated with worse clinical outcomes (coefficient=-3.858; 95% CI: -7.281 to -0.434; p=0.027) regardless of treatment.. Our results suggest that analysis of the impact of anxiety on depression outcome needs to differentiate psychic and somatic symptoms.

Topics: Antidepressive Agents; Antipsychotic Agents; Anxiety; Anxiety Disorders; Benzodiazepines; Depressive Disorder, Major; Female; Humans; Logistic Models; Male; Middle Aged; Olanzapine; Psychotic Disorders; Selective Serotonin Reuptake Inhibitors; Sertraline; Treatment Outcome

Disturbance in sleep quality is a symptom of Major Depressive Disorder (MDD) and Bipolar Disorder (BD) and thus improving quality of sleep is an important aspect of successful treatment. Here, a prospective, double-blind, randomized, placebo-controlled study examined the effect of olanzapine (an atypical antipsychotic) augmentation therapy on sleep architecture, specifically slow wave sleep (SWS), in the treatment of depression. The effect of olanzapine augmentation therapy on other features of sleep (e.g., sleep continuity) and depression (e.g., illness severity and cognitive function) were also determined.. Patients currently experiencing a major depressive episode and who were on a stable medication were included. Sleep architecture was measured by overnight ambulatory polysomnography. Illness severity was determined using the Montgomery-Asberg Depression Rating Scale (MADRS). Cognitive function was examined using Cambridge Neuropsychological Test Automated Battery (CANTAB): Spatial Working Memory (SWM), Spatial Span (SSP), and Reaction Time (RTI) tasks. Polysomnographs, clinical measures and cognitive tests were administered at baseline, after 2-4 days of treatment and after 28-31 days of treatment. Twenty-five patients participated in the study (N = 10, N = 15 for placebo and olanzapine treated groups respectively).. The primary objective of the study was to assess the objective (polysomnographic) changes in sleep quality, defined as changes in SWS, following olanzapine treatment for depression. Latency to but not duration of SWS was found to significantly differ between olanzapine- and placebo-treated participants (Hedge's g: 0.97, 0.13 respectively). A significant improvement in olanzapine-treated participants over placebo-treated participants was observed in secondary outcome measures, including sleep efficiency, total sleep time, and sleep latency. Secondary objectives assessed the subjective changes in sleep quality parameters and correlated them with measures of illness severity and changes in cognition. MADRS scores were significantly improved in olanzapine-treated participants over time but not more than placebo treatment. There was no significant difference between olanzapine- and placebo-treated participants in SWM, SSP or RTI tasks.. Olanzapine augmentation treatment generally did not improve SWS but did improve sleep continuity and depression. Olanzapine may be one of few medications that improve sleep continuity, thus directly targeting symptoms of depression.. ClinicalTrials.gov, NCT00520507.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cognition; Depressive Disorder, Major; Double-Blind Method; Female; Humans; Male; Middle Aged; Olanzapine; Prospective Studies; Sleep; Surveys and Questionnaires

Tardive dyskinesia (TD) is a debilitating adverse effect associated with antipsychotic treatment. Older age and the presence of mood disorder have been identified as risk factors for the development of TD. Thus, we assessed the incidence of TD in younger and older patients with major depressive disorder with psychotic features who participated in a 12-week clinical trial comparing olanzapine plus sertraline versus olanzapine plus placebo. All subjects (n = 259) were assessed with the Abnormal Involuntary Movement Scale at baseline and after 4, 8, and 12 weeks of treatment (or at termination). We used 7 different published criteria to estimate the prevalence of TD at baseline and the incidence over the duration of the trial. We compared the incidence of TD in subjects 60 years or older and those younger than 60 years. The overall prevalence and incidence of TD varied almost 10-fold, depending on the criteria (prevalence range, 1.2%-8.9%; incidence range, 0.0%-5.9%). Tardive dyskinesia was observed as a clinical adverse event in only 1 subject (0.4%). Whereas older subjects had a higher prevalence of TD at baseline, the incidence in younger and older subjects did not differ significantly. The incidence of TD was relatively low in both younger and older patients with major depressive disorder with psychotic features treated acutely with olanzapine. However, the estimate of the risk of TD varies widely, depending on the criteria used to define TD.

Topics: Age Factors; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Double-Blind Method; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Humans; Incidence; Middle Aged; Olanzapine; Prevalence; Psychotic Disorders; Risk Factors; Sertraline; Time Factors

Gender differences exist in psychiatric disorders; however, gender has not been well studied in psychotic depression. This analysis of the largest clinical trial in psychotic depression examined the effects of age and gender on clinical characteristics and predictors of treatment outcome and treatment-associated changes in body mass index (BMI) and metabolic measures.. Secondary analyses were performed on data from 259 subjects with major depressive disorder with psychotic features (DSM-IV-TR) aged 18-93 years in the double-blind randomized controlled trial of olanzapine plus sertraline versus olanzapine plus placebo for psychotic depression (Study of Pharmacotherapy of Psychotic Depression). Sociodemographic factors, clinical characteristics, treatment outcome, and treatment-associated changes in BMI and metabolic measures were analyzed by gender and age. Subjects were enrolled from December 2002 to June 2007.. Female gender was associated with divorced (χ(2)(1) = 5.3, P = .03) or widowed (χ(2)(1) = 8.1, P ≤ .01) marital status. Comorbid anxiety disorders were more common in women than in men (χ(2)(1) = 4.9, P = .03). Hallucinations (χ(2)(1) = 7.8, P = .005) and delusions with disorganization (t(257) = -2.10, P = .04) were significantly associated with female gender, as were higher cholesterol measures (χ(2)(1) = 7.15, P = .008). There were no significant interactions between treatment and gender in terms of change in BMI. Gender was not associated with treatment response.. This study is the first analysis of gender and age as predictors of treatment outcome and treatment-associated changes in BMI and metabolic adverse effects in psychotic depression. Gender differences exist in patients with psychotic depression, most notably with regard to the presence of hallucinations. Female gender was associated with metabolic measures. Future studies with larger sample sizes may detect small gender differences in treatment outcome and treatment-associated changes in BMI and metabolic measures in psychotic depression.. ClinicalTrials.gov identifier: NCT00056472.

Topics: Adult; Age Factors; Aged; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Body Weight; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Drug Monitoring; Drug Therapy, Combination; Female; Hallucinations; Humans; Male; Metabolism; Middle Aged; Olanzapine; Outcome Assessment, Health Care; Psychiatric Status Rating Scales; Sertraline; Sex Factors; Socioeconomic Factors; Treatment Outcome

Having failed to respond to an adequate antidepressant treatment course predicts poorer treatment outcomes in patients with major depression. However, little is known about the impact of prior treatment on the outcome of major depression with psychotic features (MDpsy). We examined the effect of prior treatment history on the outcome of pharmacotherapy of MDpsy in patients who participated in the STOPD-PD study, a randomized, double-blind, clinical trial comparing a combination of olanzapine plus sertraline vs. olanzapine plus placebo. The strength of treatment courses received prior to randomization was classified using a validated method. A hierarchy of outcomes was hypothesized based on treatments received prior to randomization and randomized treatment. A high remission rate was observed in subjects with a history of no prior treatment or inadequate treatment who were treated with a combination of olanzapine and sertraline. A low remission rate was observed in subjects who had previously failed to respond to an antidepressant alone and who were treated with olanzapine monotherapy. A low remission rate was also observed in subjects who had previously failed to respond to a combination of an antipsychotic and an antidepressant. Similar to patients with major depression, these results emphasize the impact of prior pharmacotherapy on treatment outcomes in patients with MDpsy.

Topics: Adult; Affective Disorders, Psychotic; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Resistance; Drug Therapy, Combination; Female; Humans; Male; Olanzapine; Retreatment; Sertraline

The aim of the present 12-week, open-label study was to investigate the effect of olanzapine augmentation in outpatients with depression with melancholic features who demonstrated partial response to standard antidepressants but who were reluctant to change antidepressants. The subjects consisted of 22 outpatients meeting the DSM-IV-TR criteria for major depression. Olanzapine was initially added at 2.5 mg/day and the dose was adjusted according to the clinical condition. Data were analyzed using an intention-to-treat methodology. A paired t-test was used to compare total Montgomery Asberg Depression Rating Scale (MADRS) scores before treatment, at baseline (prior to olanzapine), and 4, 8, and 12 weeks after starting olanzapine. Of 22 enrolled patients, 20 completed the trial. The mean (±SD) MADRS score was 17.1 ± 1.0 at baseline and decreased significantly to 8.1 ± 3.2 at 4 weeks after the administration of olanzapine. This significant reduction continued until 12 weeks, when the mean MADRS score was 4.9 ± 2.9, indicating full remission. These results suggest that olanzapine augmentation may be useful for patients with depression in partial remission. A controlled, double-blind trial, however, is needed to confirm these preliminary findings.

Topics: Adult; Aged; Aged, 80 and over; Antidepressive Agents; Benzodiazepines; Depressive Disorder, Major; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Olanzapine; Outpatients; Remission Induction; Selective Serotonin Reuptake Inhibitors

To evaluate the efficacy and safety of armodafinil, the longer-lasting isomer of modafinil, when used adjunctively in patients with bipolar depression.. In this 8-week, multicenter, randomized, double-blind, placebo-controlled study conducted between June 2007 and December 2008, patients who were experiencing a major depressive episode associated with bipolar I disorder (according to DSM-IV-TR criteria) despite treatment with lithium, olanzapine, or valproic acid were randomly assigned to adjunctive armodafinil 150 mg/d (n = 128) or placebo (n = 129) administered once daily in the morning. The primary outcome measure was change from baseline in the total 30-item Inventory of Depressive Symptomatology, Clinician-Rated (IDS-C₃₀) score. Secondary outcomes included changes from baseline in scores on the Montgomery-Åsberg Depression Rating Scale, among other psychological symptom scales. Statistical analyses were performed using analysis of covariance (ANCOVA), with study drug and concurrent mood stabilizer treatment for bipolar disorder as factors and the corresponding baseline value as a covariate. A prespecified sensitivity analysis was done using analysis of variance (ANOVA) if a statistically significant treatment-by-baseline interaction was found. Tolerability was also assessed.. A significant baseline-by-treatment interaction in the total IDS-C₃₀ score (P = .08) was found. Patients administered adjunctive armodafinil showed greater improvement in depressive symptoms as seen in the greater mean ± SD change on the total IDS-C₃₀ score (-15.8 ± 11.57) compared with the placebo group (-12.8 ± 12.54) (ANOVA: P = .044; ANCOVA: P = .074). No differences between treatment groups were observed in secondary outcomes. Adverse events reported more frequently in patients receiving adjunctive armodafinil were headache, diarrhea, and insomnia. Armodafinil was not associated with an increased incidence and/or severity of suicidality, depression, or mania or with changes in metabolic profile measurements.. In this proof-of-concept study, adjunctive armodafinil 150 mg/d appeared to improve depressive symptoms according to some, but not all, measures and was generally well tolerated in patients with bipolar depression.. clinicaltrials.gov Identifier: NCT00481195.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Antimanic Agents; Benzhydryl Compounds; Benzodiazepines; Bipolar Disorder; Depressive Disorder, Major; Double-Blind Method; Drug Resistance; Drug Therapy, Combination; Female; Humans; Lithium Compounds; Male; Middle Aged; Modafinil; Olanzapine; Valproic Acid

The extent of weight changes in depressed patients who use atypical antipsychotics (AAP) as augmentation could not be easily predicted due to weight related symptoms of depression and the interaction with antidepressants which have weight reducing effects.. Patients were treated with either antidepressants augmented with AAP for more than 2 weeks (AAP group, n = 100) or only with antidepressants (non-AAP group, n = 172) during the admission between 2002 and 2006, and the differences in weight were analyzed.. Mean weight gains of AAP group were significantly higher than those of non-AAP group (2.98 +/- 1.87 kg vs. 1.70 +/- 1.85 kg, p = 0.001). When stratified by antidepressants, the significant difference between the two groups was shown among the subjects who had taken serotonin reuptake inhibitors (SSRIs), but not mirtazapine and venlafaxine (3.42 +/- 2.01 kg vs. 1.48 +/- 1.79 kg, p < 0.001). Comparing among different combinations in AAP group showed that subjects treated with SSRIs and olanzapine had the greatest weight gain (4.21 +/- 1.90 kg), significantly higher than that of the other subgroups (p < 0.001).. Our findings suggest that AAP used in patients with depression could severely aggravate preexisting weight-related problems of antidepressants use and the possibility that the combined use with specific antidepressants could have a unique effect on weight by drug-drug interactions.

Topics: Adult; Aged; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Cyclohexanols; Depressive Disorder, Major; Drug Interactions; Drug Therapy, Combination; Female; Humans; Male; Mianserin; Middle Aged; Mirtazapine; Olanzapine; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride; Weight Gain

Evidence for the efficacy of combination pharmacotherapy has been limited and without positive trials in geriatric patients with major depression (MD) with psychotic features.. To compare remission rates of MD with psychotic features in those treated with a combination of atypical antipsychotic medication plus a serotonin reuptake inhibitor with those treated with antipsychotic monotherapy; and to compare response by age.. Twelve-week, double-blind, randomized, controlled trial.. Clinical services of 4 academic sites. Patients Two hundred fifty-nine subjects with MD with psychotic features randomized by age (<60 or > or =60 years) (mean [standard deviation (SD)], 41.3 [10.8] years in 117 younger adults vs 71.7 [7.8] years in 142 geriatric participants). Intervention Target doses of 15 to 20 mg of olanzapine per day plus masked sertraline or placebo at 150 to 200 mg per day. Main Outcome Measure Remission rates of MD with psychotic features.. Treatment with olanzapine/sertraline was associated with higher remission rates during the trial than olanzapine/placebo (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.12-1.47; P < .001); 41.9% of subjects who underwent combination therapy were in remission at their last assessment compared with 23.9% of subjects treated with monotherapy (chi(2)(1) = 9.53, P = .002). Combination therapy was comparably superior in both younger (OR, 1.25; 95% CI, 1.05-1.50; P = .02) and older (OR, 1.34; 95% CI, 1.09-1.66; P = .01) adults. Overall, tolerability was comparable across age groups. Both age groups had significant increases in cholesterol and triglyceride concentrations, but statistically significant increases in glucose occurred only in younger adults. Younger adults gained significantly more weight than older subjects (mean [SD], 6.5 [6.6] kg vs 3.3 [4.9] kg, P = .001).. Combination pharmacotherapy is efficacious for the treatment of MD with psychotic features. Future research must determine the benefits vs risks of continuing atypical antipsychotic medications beyond 12 weeks.. clinicaltrials.gov Identifier: NCT00056472.

Topics: Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Double-Blind Method; Drug Therapy, Combination; Humans; Olanzapine; Placebos; Psychotic Disorders; Selective Serotonin Reuptake Inhibitors; Sertraline; Treatment Outcome

Two parallel, 8-week double-blind studies compared olanzapine/fluoxetine combination, olanzapine, and fluoxetine in outpatients with treatment-resistant depression (TRD).. Treatment-resistant depression was defined as a documented history of current-episode antidepressant failure plus a prospective failure on fluoxetine. Following an 8-week fluoxetine lead-in, 605 nonresponders with DSM-IV major depressive disorder were randomly assigned to olanzapine/fluoxetine combination, olanzapine, or fluoxetine. The primary outcome measure was baseline-to-endpoint mean change on the Montgomery-Asberg Depression Rating Scale (MADRS). The study was conducted from April 2002 to May 2005.. After 8 weeks of double-blind treatment, Study 1 revealed no statistically significant therapy differences in MADRS mean change (olanzapine/fluoxetine combination: -11.0, fluoxetine: -9.4, olanzapine: -10.5). In Study 2, olanzapine/fluoxetine combination demonstrated significantly greater MADRS improvement (-14.5) than fluoxetine (-8.6, p < .001) and olanzapine (-7.0, p < .001). Pooled study results revealed significant differences for olanzapine/ fluoxetine combination (-12.7) versus fluoxetine (-9.0, p < .001) and olanzapine (-8.8, p < .001). Pooled remission rates were 27% for olanzapine/ fluoxetine combination, 17% for fluoxetine, and 15% for olanzapine. Adverse events were consistent with previous studies. Cholesterol mean change (mg/dL) was +15.1 for olanzapine/ fluoxetine combination, +0.8 for fluoxetine, and +2.7 for olanzapine. Mean weight change (kg) was +4.9 for olanzapine/fluoxetine combination, +0.4 for fluoxetine, and +5.5 for olanzapine. Nonfasting glucose mean change (mg/dL) was +11.4 for olanzapine/fluoxetine combination, +4.9 for fluoxetine, and +9.9 for olanzapine.. Patients with TRD (defined as treatment failure on 2 antidepressants) taking olanzapine/fluoxetine combination demonstrated significantly greater improvement in depressive symptoms than patients taking olanzapine or fluoxetine in 1 of 2 studies and in the pooled analysis. When considered within the context of all available evidence, olanzapine/fluoxetine combination is an efficacious therapy for patients with TRD.. ClinicalTrials.gov identifier: NCT00035321.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Double-Blind Method; Drug Resistance; Drug Therapy, Combination; Female; Fluoxetine; Humans; Male; Middle Aged; Olanzapine; Selective Serotonin Reuptake Inhibitors; Treatment Failure

The Treatment of Early Onset Schizophrenia Spectrum Disorders Study is a publicly funded clinical trial designed to compare the therapeutic benefits, safety, and tolerability of risperidone, olanzapine, and molindone in youths with early-onset schizophrenia spectrum disorders. The rationale, design, and methods of the Treatment of Early Onset Schizophrenia Spectrum Disorders Study are described.. Using a randomized, double-blind, parallel-group design at four sites, youths with EOSS (ages 8-19 years) were assigned to an 8-week acute trial of risperidone (0.5-6.0 mg/day), olanzapine (2.5-20 mg/day), or molindone (10-140 mg/day). Responders continued double-blind treatment for 44 weeks. The primary outcome measure was responder status at 8 weeks, defined by a 20% reduction in baseline Positive and Negative Symptom Scale scores plus ratings of significant improvement on the Clinical Global Impressions. Secondary outcome measures included assessments of psychopathology, functional impairment, quality of life, and medication safety. An intent-to-treat analytic plan was used.. From February 2002 to May 2006, 476 youths were screened, 173 were further evaluated, and 119 were randomized. Several significant study modifications were required to address safety, the use of adjunctive medications, and the termination of the olanzapine treatment arm due to weight gain.. The Treatment of Early Onset Schizophrenia Spectrum Disorders Study will inform clinical practice regarding the use of antipsychotic medications for youths with early-onset schizophrenia spectrum disorders. Important safety concerns emerged during the study, including higher than anticipated rates of suicidality and problems tapering thymoleptic agents before randomization.

Topics: Adolescent; Adult; Age of Onset; Antipsychotic Agents; Benzodiazepines; Child; Comorbidity; Depressive Disorder, Major; Double-Blind Method; Female; Humans; Male; Molindone; Olanzapine; Risperidone; Schizophrenia; Time Factors

In this pilot study we assessed the efficacy of olanzapine as monotherapy in the treatment of major depressive disorder, without psychosis. We also demonstrated the in vivo 5-HT2A receptor occupancy of olanzapine using positron emission tomography. An open-label prospective 6-week study design with 14 patients who met the inclusion and exclusion criteria for the study were enrolled from the general community of the St. Louis metropolitan area. All patients met DSM-IV criteria for major depressive disorder without psychosis, had a Hamilton Depression Rating Scale (HAMD17) score >18 and were between the ages of 18 and 65. The primary measure of efficacy was the change in HAMD 17 total score from baseline to endpoint. The data were collected between 1998 and 2004. There was a significant reduction in the HAMD17 scores from baseline to endpoint. Half the patients (n=6) showed > or =50% reduction in their HAMD17 scores. This study points to the potential of olanzapine as a therapeutic agent for the treatment of major depressive disorder without psychosis.

Topics: Antidepressive Agents; Benzodiazepines; Brain; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Drug Administration Schedule; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Olanzapine; Pilot Projects; Positron-Emission Tomography; Prospective Studies; Receptor, Serotonin, 5-HT2A; Severity of Illness Index

Based on preliminary evidence of its usefulness in treatment-resistant depression (TRD), an olanzapine/fluoxetine combination (OFC) was examined in comparison with olanzapine, fluoxetine, and venlafaxine in a TRD population. In this 12-week double-blind study, 483 subjects with unipolar, nonpsychotic TRD, with historic failure on a selective serotonin reuptake inhibitor (SSRI) and prospective failure on open-label venlafaxine, were randomized to an OFC or to an olanzapine, fluoxetine, or venlafaxine monotherapy group. Venlafaxine was continued randomly in the double-blind acute phase to explore the benefits of continuation versus switching therapy. The Montgomery-Asberg Depression Rating Scale (MADRS) total change score at end point was the primary outcome measure. The OFC group had significantly greater improvement in depressive symptoms by week 1 of treatment (MADRS mean change =-7.2, baseline =29.6), in comparison to olanzapine (-4.8, P=.03), fluoxetine (-4.7, P=.03), or venlafaxine (-3.7, P=.002) groups and maintained its statistical separation from all three monotherapy groups through week 6. At end point, the OFC group was significantly different only from the olanzapine group (-14.1 vs. -7.7, P<.001). Analysis of a subgroup of subjects who had an SSRI failure in their current depressive episode (n=334) revealed statistical separation from both olanzapine and fluoxetine (but not venlafaxine) at end point: OFC (-14.6) versus olanzapine (-9.4, P<.001) versus fluoxetine (-10.7, P=.006) versus venlafaxine (-14.7, P=.98). The OFC had a safety profile comparable to its component monotherapies (i.e., olanzapine and fluoxetine), showed a rapid onset of antidepressant effect, and was effective in this TRD sample. At the study end point, OFC, fluoxetine, venlafaxine, and low-dose OFC all appeared to be similarly effective.

Topics: Benzodiazepines; Brief Psychiatric Rating Scale; Cyclohexanols; Depressive Disorder, Major; Double-Blind Method; Drug Administration Schedule; Drug Resistance; Drug Therapy, Combination; Female; Fluoxetine; Humans; Male; Mass Screening; Middle Aged; Olanzapine; Prospective Studies; Remission Induction; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index; Treatment Refusal; Venlafaxine Hydrochloride

We report here a study examining the relationships between insight and psychopathology, cognitive performance, brain volume and co-morbid depression in 251 patients experiencing a first episode of psychosis, who were then randomly assigned to 2 years of double-blind treatment with either olanzapine or haloperidol.. Repeated measures of insight were obtained at baseline and 12, 24, 52 and 104 weeks by the Insight and Treatment Attitudes Questionnaire (ITAQ).. Older age, female gender and white ethnicity were associated with more insight. Higher total, positive, negative and general psychopathology scores on the Positive and Negative Syndromes Scale (PANSS) were associated with less insight. Higher depression scores were associated with more insight. Better neurocognitive function and large brain volumes were associated with more insight. More insight throughout the study was associated with longer time to medication non-adherence. However, baseline insight was not significantly related to the probability of discontinuing the study before 2 years. Insight improved significantly over the course of the study, but the improvement in insight was not significantly different between the two antipsychotic treatment groups.. Multiple factors contribute to insight. Patients experiencing a first episode of psychosis who have little insight are at increased risk of discontinuing their medication.

Topics: Adolescent; Adult; Antipsychotic Agents; Attitude to Health; Benzodiazepines; Brain; Cognition Disorders; Depressive Disorder, Major; Double-Blind Method; Female; Haloperidol; Humans; Male; Neuropsychological Tests; Olanzapine; Psychotic Disorders; Surveys and Questionnaires; Treatment Refusal

Although delusions are the hallmark of major depression with psychotic features, a scale to measure the intensity of beliefs across multiple delusional domains in this condition has been unavailable. The development and assessment of the Delusional Assessment Scale (DAS) are described.. Scale items were selected initially based on previous studies of delusional ideation in schizophrenia. A three-point item to assess mood congruence was added. A 15-item scale was assessed in 92 subjects participating in the four-site collaborative study of the pharmacotherapy of major depression with psychotic features. Maximum likelihood method was used to determine scale factors. The internal consistency of these factors was determined. Comparisons between scale scores and ratings from the Brief Psychiatric Rating Scale (BPRS) (Overall and Gorham 1962) were used to assess convergent and discriminant validity.. The data were fit by a five-factors model (impact, conviction, disorganization, bizarreness, and extension). Inter-rater reliability of the five factors ranged from .77 for conviction and .74 for impact to .37 for disorganization. Internal consistency for each of the five factors was > or =.72. Scores on specific domains were significantly correlated with the BPRS unusual thought content item and positive symptom subscale scores.. The DAS is a reliable measure of 5 delusional domains.

Topics: Adult; Affect; Antipsychotic Agents; Benzodiazepines; Delusions; Depressive Disorder, Major; Double-Blind Method; Female; Humans; Male; Observer Variation; Olanzapine; Principal Component Analysis; Psychiatric Status Rating Scales; Reproducibility of Results; Selective Serotonin Reuptake Inhibitors; Sertraline

To assess whether pharmacokinetic drug interactions occur when sertraline is added to antipsychotic medications.. Forty-eight patients with remitted DSM-IV schizophrenia and comorbid major depression were randomized to placebo for 6 weeks or sertraline 50 mg for 4 weeks followed by sertraline 50 mg to 100 mg for 2 weeks for nonresponders. Treatment with the patients' usual antipsychotic continued. Weekly clinical outcome assessments occurred for 6 weeks, and serum samples for drug monitoring were collected at Weeks 1, 5, and 6. Serum concentrations of sertraline and antipsychotics were measured with standard assays.. In both placebo- and sertraline-treated groups, most patients displayed minor fluctuations in antipsychotic serum levels over 6 weeks. There was no clinical evidence of drug interactions in the sertraline-treated group.. Clinically significant adverse effects did not occur despite variable antipsychotic serum levels with or without sertraline. Concern about pharmacokinetic interactions should not deter the use of sertraline for depression in individuals with schizophrenia.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Comorbidity; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Drug Monitoring; Humans; Middle Aged; Olanzapine; Psychotic Disorders; Risperidone; Schizophrenia; Selective Serotonin Reuptake Inhibitors; Sertraline

The authors' goal was to determine if prescription of antidepressant medication plus olanzapine initiates a more rapid response than prescription of antidepressant alone.. Twenty patients with major depression were studied. For 2 weeks the patients were blindly assigned to receive antidepressant plus olanzapine or antidepressant plus placebo. After 2 weeks, olanzapine augmentation was initiated for patients who did not improve with placebo augmentation. Response to medication was measured primarily by Hamilton Depression Rating Scale score. Other measures were the CORE, Clinical Global Impression, Beck Depression Inventory, and Daily Rating Schedule.. Hamilton depression scores improved nonsignificantly in response to olanzapine combination therapy, but that trend was not evident on any secondary measure. Four patients who did not improve while receiving antidepressant and placebo showed rapid remission following late olanzapine augmentation.. Failure to demonstrate any benefit from initial combination therapy may reflect an underpowered rather than a negative study. The distinct impact of late olanzapine augmentation suggests that pretreatment with an antidepressant may be required to facilitate a rapid antidepressant response to combined treatment.

Topics: Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Olanzapine; Personality Inventory; Pilot Projects; Placebos; Psychiatric Status Rating Scales; Severity of Illness Index; Time Factors; Treatment Outcome

Olanzapine is the most commonly prescribed atypical antipsychotic medication in Australia. Research reports an average weight gain of between 4.5 and 7 kg in the 3 months following its commencement. Trying to minimize this weight gain in a population with an already high prevalence of obesity, mortality and morbidity is of clinical and social importance. This randomized controlled trial investigated the impact of individual nutrition education provided by a dietitian on weight gain in the 3 and 6 months following the commencement of olanzapine.. Fifty-one individuals (29 females, 22 males) who had started on olanzapine in the previous 3 months (mean length of 27 days +/- 20) were recruited through Peninsula Health Psychiatric Services and were randomly assigned to either the intervention (n = 29) or the control group (n = 22). Individuals in the intervention group received six 1 hour nutrition education sessions over a 3-month period. Weight, waist circumference, body mass index (BMI) and qualitative measures of exercise levels, quality of life, health and body image were collected at baseline at 3 and 6 months.. After 3 months, the control group had gained significantly more weight than the treatment group (6.0 kg vs 2.0 kg, p < or = 0.002). Weight gain of more than 7% of initial weight occurred in 64% of the control group compared to 13% of the treatment group. The control group's BMI increased significantly more than the treatment group's (2 kg/m(2)vs 0.7 kg/m(2), p < or = 0.03). The treatment group reported significantly greater improvements in moderate exercise levels, quality of life, health and body image compared to the controls. At 6 months, the control group continued to show significantly more weight gain since baseline than the treatment group (9.9 kg vs 2.0 kg, p < or = 0.013) and consequently had significantly greater increases in BMI (3.2 kg/m(2)vs 0.8 kg/m(2), p < or = 0.017).. Individual nutritional intervention provided by a dietitian is highly successful at preventing olanzapine-induced weight gain.

Topics: Adult; Benzodiazepines; Bipolar Disorder; Body Image; Body Mass Index; Depressive Disorder, Major; Exercise; Female; Health Status; Humans; Male; Nutritional Physiological Phenomena; Obesity; Olanzapine; Quality of Life; Schizophrenia; Weight Gain

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 8-week, double-blind, multicenter study was undertaken to replicate, in a larger sample of patients with treatment-resistant major depressive disorder (MDD; DSM-IV criteria), the results of a pilot study of the olanzapine/fluoxetine combination.. The study was begun in August 1999. The primary entry criterion was a history of failure to respond to a selective serotonin reuptake inhibitor (SSRI). Patients (N = 500) who subsequently failed to respond to nortriptyline during an open-label lead-in phase were randomly assigned to 1 of 4 treatment groups: olanzapine (6-12 mg/day) plus fluoxetine (25-50 mg/day) combination, olanzapine (6-12 mg/day), fluoxetine (25-50 mg/day), or nortriptyline (25-175 mg/day). The primary outcome measure was baseline-to-endpoint mean change in score on the Montgomery-Asberg Depression Rating Scale (MADRS).. At the 8-week study endpoint, MADRS total scores decreased by a mean 8.7 points from baseline (28.5) with the olanzapine/fluoxetine combination, 7.0 points from baseline (28.4) with olanzapine (p = .08), 8.5 points from baseline (28.4) with fluoxetine (p = .84), and 7.5 points from baseline (28.8) with nortriptyline (p = .30), with no significant differences among the therapies. The olanzapine/fluoxetine combination was associated with significantly (p < or = .05) greater improvement (decrease) in MADRS scores than olanzapine at weeks 2, 4, 6, and 7; than fluoxetine at weeks 2 through 5; and than nortriptyline at weeks 1 through 4. A post hoc analysis of a subgroup of patients who had an SSRI treatment failure during their current MDD episode (N = 314) revealed that the olanzapine/fluoxetine combination group had a significantly (p = .005) greater decrease in MADRS scores than the olanzapine group at endpoint. Safety data for the olanzapine/fluoxetine combination were similar to those for its component monotherapies.. The olanzapine/fluoxetine combination did not differ significantly from the other therapies at endpoint, although it demonstrated a more rapid response that was sustained until the end of treatment. The results raised several methodological questions, and recommendations are made regarding the criteria for study entry and randomization.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Drug Combinations; Drug Resistance; Drug Therapy, Combination; Female; Fluoxetine; Humans; Male; Nortriptyline; Olanzapine; Pilot Projects; Placebos; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

Patients with major depressive disorder (MDD) treated with olanzapine in combination with fluoxetine (OFC) demonstrate robust improvement in their depressive symptoms. Treatment with olanzapine may impact a patient's weight; thus, long-term weight gain and potential predictors (e.g., age and gender) and correlates (e.g., cholesterol and glucose levels) of weight gain were investigated in OFC-treated patients with MDD.. Outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnostic criteria for MDD were included (N = 549) in the current analyses of this 76-week, open-label study (February 2000 to July 2002). Maximum, endpoint, and potentially clinically significant (PCS; > or = 7% increase from baseline) weight gain; time to PCS weight gain; and predictors and correlates of weight change were assessed. Patients were treated once daily with oral olanzapine (6, 12, or 18 mg) plus fluoxetine (25, 50, or 75 mg) capsules. Statistical significance for all tests was based upon p < or = .05.. Mean baseline-to-endpoint weight change was 5.6 +/- 6.6 kg (12.3 +/- 14.6 lb). Weight gain plateaued by 52 weeks. Fifty-six percent of patients met criteria for PCS weight gain by 76 weeks, and the median time to PCS weight gain was 16 weeks. Low baseline body mass index (BMI), female gender, younger age, and increased fluoxetine dose were predictors of weight gain; olanzapine dose was not. Patients with early (< or = 6 weeks) rapid PCS weight gain were 4.6 times more likely to gain substantial (> or = 15%) weight long-term (weeks 7-76). Changes to endpoint in total cholesterol and systolic blood pressure values were positively correlated with weight change.. Long-term (76 weeks) OFC treatment may lead to a large percentage (56%) of patients meeting criteria for PCS weight gain (> or = 7%). The risk of weight gain may be significantly increased for OFC-treated patients who have a low BMI or who are female, younger, or taking high-dose fluoxetine. It is important that prescribers balance the risk of weight gain with the benefit of treatment for individual patients with depression.

Topics: Adult; Ambulatory Care; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Depressive Disorder, Major; Diabetes Mellitus; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluoxetine; Follow-Up Studies; Humans; Male; Obesity; Olanzapine; Regression Analysis; Risk Factors; Selective Serotonin Reuptake Inhibitors; Time Factors; Treatment Outcome; Weight Gain

The purpose of the present paper was to investigate the effects of the dopamine agonist amantadine in those patients with weight gain induced by olanzapine. An open trial was conducted in those patients who gained >3 kg in weight induced by olanzapine use. All subjects were evaluated by weight, body mass index (BMI), the Brief Psychiatric Rating Scale (BPRS), and the Extrapyramidal Symptom Rating Scale (ESRS) before and after the use of amantadine in addition to olanzapine. Twenty-five of 30 enrolled patients completed the present study. Mean bodyweight and BMI was increased by 6.44 +/- 4.42 kg and 5.04 +/- 3.47 kg/m2 significantly with olanzapine alone (P < 0.001). When amantadine and olanzapine were used together, the average weight and BMI decreased by 1.07 +/- 3.19 kg and 0.84 +/- 2.5 kg/m2, but did not have statistical significance. The average values of BPRS showed a significant decrease (P < 0.001). No significant changes were present in ESRS. Amantadine did not have an effect on weight gain induced by olanzapine. Randomized placebo-controlled prospective studies are needed.

Topics: Adult; Amantadine; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Body Mass Index; Body Weight; Brief Psychiatric Rating Scale; Depressive Disorder, Major; Dopamine Agonists; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Neurologic Examination; Olanzapine; Psychotic Disorders; Schizophrenia; Treatment Outcome

The purpose of this study was to compare the efficacy and safety of olanzapine (OLZ) monotherapy and an olanzapine/fluoxetine combination (OFC) with placebo (PLA) for unipolar major depression with psychotic features. Under a single protocol, two 8-week, double-blind trials were conducted at 27 sites. Patients (n = 124 trial 1, n = 125 trial 2) were randomized to 1 of 3 treatment groups: OLZ (5 to 20 mg/d), PLA, or OFC (olanzapine 5 to 20 mg/d + fluoxetine 20 to 80 mg/d). The primary outcome measure was the 24-item Hamilton Depression Rating Scale total score. For trial 1, endpoint improvement for the OLZ group (-14.9) was not significantly different from the PLA or OFC groups. The OFC group had significantly greater endpoint improvement (-20.9) than the PLA group (-10.4, P = 0.001); this significant difference was present within 7 days of therapy and maintained at every subsequent visit. The OFC group also had significantly higher response rate (63.6%) than the PLA (28.0%, P = 0.004) or OLZ (34.9%, P = 0.027) groups. For trial 2, there were no significant differences among treatment groups on the 24-item Hamilton Depression Rating Scale total scores or response rates. The combination exhibited a comparable safety profile with OLZ monotherapy and no significant increases in extrapyramidal symptoms compared with placebo. Patients with major depression with psychotic features treated with OLZ monotherapy did not demonstrate significant depressive symptom improvement compared with placebo in either trial; however, an olanzapine/fluoxetine combination was associated with significant improvement compared with placebo in one trial and was well tolerated.

Topics: Adult; Analysis of Variance; Benzodiazepines; Chi-Square Distribution; Depressive Disorder, Major; Double-Blind Method; Drug Therapy, Combination; Female; Fluoxetine; Humans; Male; Middle Aged; Olanzapine; Psychotic Disorders

The first double-blind placebo-controlled clinical trial of an atypical neuroleptic medication is being conducted in symptomatic treatment-seeking patients meeting new diagnostic criteria for a putative prodromal syndrome. This identifies them as being at high risk for developing psychosis in the near future. The study aims include prevention of psychosis onset and disability, as well as palliation of ongoing symptomatology. The purpose of this report is to describe the study's "prodromally symptomatic" sample at baseline, i.e., at intake immediately prior to randomization and prior to receiving study medication. Sixty treatment-seeking patients meeting prodromal inclusion criteria were recruited across four sites: New Haven, CT (n=39), Toronto, Ontario (n=9), Calgary, Alberta (n=6), and Chapel Hill, NC (n=6). The sample was young (median age 16), largely male (65%), and came from families with high titers of serious mental illness (44%). Most patients (93%) met criteria for the Attenuated Positive Symptom (APS) prodromal syndrome and presented with significant but nonpsychotic suspiciousness, perceptual aberrations, unusual thought content, and conceptual disorganization. They presented with minimal to mild affective symptoms and substance use/abuse, but they were quite functionally compromised (mean Global Assessment of Functioning (GAF) score=42). The prodromal sample was compared with other clinical-trial samples of adolescent depression, adolescent mania, and first episode schizophrenia. Prodromal patients proved not to be depressed or manic. They were less severely ill than untreated first episode schizophrenia but more severely ill than treated first episode schizophrenia. While not psychotically disabled, these patients nevertheless present with a clinical syndrome. Subsequent reports will detail the effects of drug versus placebo on prodromal symptoms, neuropsychological profile, and the rate of conversion to psychosis.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Comorbidity; Depressive Disorder, Major; Double-Blind Method; Female; Humans; Male; Mood Disorders; Olanzapine; Pirenzepine; Psychomotor Disorders; Psychotic Disorders; Risk Factors; Schizophrenia; Schizophrenic Psychology; Sleep Wake Disorders; Speech Disorders

Although atypical antipsychotic agents are commonly used in the treatment of psychotic depression, there are no published prospective studies on their use in this condition. The aim of this study was to assess, by interim analyses, the efficacy of the atypical antipsychotic agent olanzapine in combination with the selective serotonin reuptake inhibitor antidepressant agent fluoxetine.. We enrolled 27 patients (17 women [63.0%] and 10 men [37.0%]; mean +/- SD age: 41.2 +/- 14.7 years) with DSM-IV-defined major depressive disorder with psychotic features into an open trial of olanzapine, 5 to 20 mg/day, plus fluoxetine, 20 to 80 mg/day. Patients were assessed at each visit with the 17-item Hamilton Rating Scale for Depression and both the psychotic and mood modules of the Structured Clinical Interview for DSM-IV Axis I Disorders, Patient Edition. We are reporting the results of the first 6 weeks of treatment.. Twenty-two (81.5%) of the 27 enrolled patients completed the 6-week open trial, and 5 (18.5%) dropped out, with only 2 (7.4%) dropping out due to side effects. Of the 27 patients, 74.1% (N = 20) met criteria for melancholic features, 14.8% (N = 4) had delusions alone, 18.5% (N = 5) had hallucinations alone, and 66.7% (N = 18) reported both delusions and hallucinations. In addition, the overall rates of response for the intent-to-treat group were as follows: depression response rate, 66.7% (N = 18); psychosis response rate, 59.3% (N = 16); psychotic depression response rate, 55.6% (N = 15); and psychotic depression remission rate, 40.7% (N = 11).. The combination of olanzapine and fluoxetine appears to be a promising, safe, and effective treatment for psychotic depression. Double-blind studies are needed to confirm this impression.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Female; Fluoxetine; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders

Compared to major depression without psychosis, psychotic depression often responds poorly to treatment with tricyclic antidepressants alone. Atypical antipsychotics, which appear to possess thymoleptic properties, may represent a new treatment alternative for patients with psychotic mood disorders. This open-label, pilot study evaluated the efficacy of olanzapine monotherapy in patients with psychotic depression. Seven inpatients who met DSM-IV criteria for a major depressive episode (unipolar) with psychotic features participated in a 10-week open-label trial of olanzapine 10-20 mg/day. The Hamilton Rating Scale for Depression (HRSD), the Scale for the Assessment of Positive Symptoms (SAPS), and the Clinical Global Impression Scale (CGI) were performed at each visit to evaluate clinical response. Four out of the 5 study completers responded during the trial. Overall, there was a statistically significant change between baseline and final visit on the SAPS, HRSD, and the CGI Scale (p < .001). The results of this pilot study suggest that olanzapine may be an effective treatment for some patients with unipolar psychotic depression. However, these observations require replication in randomized, controlled trials.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Female; Humans; Male; Olanzapine; Pilot Projects; Pirenzepine; Psychiatric Status Rating Scales; Psychotic Disorders; Treatment Outcome

Topics: Adult; Adult Survivors of Child Abuse; Antidepressive Agents; Antipsychotic Agents; Depressive Disorder, Major; Desvenlafaxine Succinate; Eye Movement Desensitization Reprocessing; Female; Humans; Olanzapine; Paranoid Disorders; Psychotic Disorders; Stress Disorders, Post-Traumatic

Neuroleptic malignant syndrome (NMS) is a life-threatening neurological emergency that is primarily characterized by altered consciousness, hyperpyrexia, muscular rigidity, and autonomic instability. Here, we describe a unique case of NMS. A 54-year-old woman with major depressive disorder (MDD) was admitted to our hospital to relieve painful emotions; her laboratory tests and physical examinations were unremarkable. Her medication regime was as follows: day 1, quetiapine (200 mg), clonazepam (2 mg), and zopiclone (7.5 mg); day 2, olanzapine (5 mg) and sertraline (100 mg); day 3, olanzapine (15 mg), sertraline (100 mg), zopiclone (7.5 mg), and clonazepam (2 mg); day 4, olanzapine (15 mg) and haloperidol (5 mg); and day 5, sertraline (50 mg) and olanzapine (5 mg). The patient then developed NMS, and a series of tests showed further abnormalities. Unusually, her cardiac troponin I (TNI) was abnormally elevated as her NMS symptoms worsened, but gradually decreased after she was transferred to the cardiology department for treatment. The increased TNI was suspected to be related to the NMS. Here, we provide several potential explanations for the relationship between TNI and NMS. Based on the present case, it may be important to measure and monitor TNI concentrations in NMS patients.

Topics: Antipsychotic Agents; Depressive Disorder, Major; Female; Humans; Middle Aged; Neuroleptic Malignant Syndrome; Olanzapine; Troponin I

Topics: Depression; Depressive Disorder, Major; Humans; Olanzapine; Psychotic Disorders; Recurrence

Antipsychotic drug use among children and adolescents is increasing, and there is growing concern about off-label use and adverse effects. The present study aims to investigate the incidence, psychiatric co-morbidity and pharmacological treatment of severe mental disorder in Norwegian children and adolescents.. We obtained data on mental disorders from the Norwegian Patient Registry on 0-18 year olds who during 2009-2011 were diagnosed for the first time with schizophrenia-like disorder (International Classification of Diseases, 10th revision codes F20-F29), bipolar disorder (F30-F31), or severe depressive episode with psychotic symptoms (F32.3 or F33.3). Data on filled prescriptions for psychotropic drugs were obtained from the Norwegian Prescription Database.. A total of 884 children and adolescents (25.1 per 100 000 person years) were first time diagnosed with schizophrenia-like disorder (12.6 per 100 000 person years), bipolar disorder (9.2 per 100 000 person years), or severe depressive episode with psychotic symptoms (3.3 per 100 000 person years) during 2009-2011. The most common co-morbid mental disorders were depressive (38.1%) and anxiety disorders (31.2%). Antipsychotic drugs were prescribed to 62.4% of the patients, 72.0% of the schizophrenia-like disorder patients, 51.7% of the bipolar disorder patients, and 55.4% of the patients with psychotic depression. The most commonly prescribed drugs were quetiapine (29.5%), aripiprazole (19.6%), olanzapine (17.3%), and risperidone (16.6%).. When a severe mental disorder was diagnosed in children and adolescents, the patient was usually also prescribed antipsychotic medication. Clinicians must be aware of the high prevalence of depressive and anxiety disorders among early psychosis patients.

Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Child; Child, Preschool; Comorbidity; Depressive Disorder, Major; Female; Humans; Incidence; Infant; Male; Mental Disorders; Norway; Olanzapine; Prevalence; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia

We conducted a 12-week double-blind study of stabilization pharmacotherapy in patients with remitted psychotic depression (PD).. Seventy-one persons aged 18 years or older who had achieved remission of PD when randomized to either olanzapine plus sertraline or olanzapine plus placebo were continued on the double-blind treatment associated with remission. Symptoms of depression and psychosis, and weight, were measured once every 4 weeks. Cholesterol, triglycerides, and glucose were measured at stabilization phase baseline and Week 12/termination.. The effect of treatment did not significantly change with time for depression, weight, or metabolic measures in the stabilization phase. Eight of the 71 participants (11.3%; 95% CI: 5.8, 20.7) experienced a relapse of major depression, psychosis, or both. Treatment groups did not differ in the frequency of relapse. In the entire study group, the adjusted estimate for change in weight was an increase of 1.66 kg (95% CI: 0.83, 2.48) and the adjusted estimate for change in total cholesterol was a decrease of 14.8 mg/dL (95% CI: 3.5, 26.1) during the 12-week stabilization phase; the remaining metabolic measures did not significantly change.. Continuation of acute treatment was associated with stability of remission.

Topics: Adult; Aged; Antidepressive Agents; Antipsychotic Agents; Blood Glucose; Body Weight; Cholesterol; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Olanzapine; Placebos; Psychotic Disorders; Remission Induction; Sertraline; Triglycerides

Electroconvulsive Therapy (ECT) of a 15-year-old female patient suffering from a severe delusional depression: a case report Abstract.. Electroconvulsive Therapy (ECT) is a modern therapy of severe psychiatric disorders. However, ECT is rarely used in treating children and adolescents with psychiatric disorders. This case report refers about a 15-year-old female patient suffering from severe depressive episodes with psychotic symptoms treated with ECT.. After unsuccessful combined behavioral therapy and medication, the patient received a total of 11 ECT treatments with right unilateral electrode placement. The severity of depressive symptoms was assessed by self (BDI-II) and external (HDRS21) scores before, during and after treatment.. A rapid decline of depressive symptoms was observed.. ECT provides a safe and effective method for the treatment of severe depressive disorders in childhood and adolescence and should be included earlier than usual into the standard therapeutic concepts.. Zusammenfassung. Fragestellung: Die Elektrokonvulsionstherapie (EKT) ist ein modernes Therapieverfahren für schwere psychiatrische Erkrankungen. Die EKT findet jedoch nur selten Anwendung bei Kindern und Jugendlichen. Dieser Fallbericht handelt von der Anwendung der EKT bei einer 15-jährigen Patientin mit einer schweren depressiven Episode mit psychotischen Symptomen. Methodik: Nach erfolgloser kombinierter verhaltenstherapeutischer und medikamentöser Behandlung erhielt die Patientin insgesamt 11 EKT-Behandlungen mit rechts unilateraler Elektrodenplatzierung. Vor, während und nach dem Behandlungszeitraum wurde mittels Eigen- (BDI-II) und Fremdurteil (HDRS21) das Ausmaß der Depressivität bestimmt. Ergebnisse: Klinisch konnte ein schneller und deutlicher Rückgang der depressiven Symptomatik festgestellt werden. Schlussfolgerungen: Der Einsatz einer EKT sollte im Rahmen eines Gesamtbehandlungskonzepts für schwere psychiatrische Störungen bei Kindern und Jugendlichen frühzeitig erwogen werden.

Topics: Adolescent; Combined Modality Therapy; Depressive Disorder, Major; Electroconvulsive Therapy; Female; Follow-Up Studies; Humans; Olanzapine; Patient Admission; Schizophrenia, Paranoid; Suicide, Attempted

Antipsychotics produce electroencephalogram (EEG) modifications and increase the risk of epileptic seizure. These modifications remain sparsely studied specifically for atypical antipsychotics. In this context, our study focuses on EEG modifications associated with atypical strict antipsychotic monotherapies.. Electroencephalogram recordings of 84 psychiatric patients treated with atypical antipsychotics in strict monotherapy (clozapine, n = 22; aripiprazole, n = 22; olanzapine, n = 17; risperidone, n = 9; quetiapine, n = 8; risperidone long-acting injection, n = 4; and paliperidone long-acting injection, n = 2) were analyzed. The modifications were ranked according to both slowing and excitability scores.. Electroencephalogram modifications (in 51 subjects, 60.71%) were graded according to 4 stages combining general slowing and sharp slow waves and/or epileptiform activities. The presence of sharp or epileptiform activities was significantly greater for clozapine (90.9%) compared with other second-generation antipsychotics (aripiprazole, 50%; olanzapine, 58.8%; quetiapine, 37.5%; risperidone, 44.4%). Age, duration of disease progression, and diagnosis were not associated as risk factors. Electroencephalogram modifications were associated with lower doses for treatment with quetiapine but not for specific antipsychotics. Electroencephalogram modifications and severe excitability were associated with higher chlorpromazine equivalent doses.. Atypical antipsychotics (clozapine, aripiprazole, quetiapine, olanzapine, and risperidone) induce EEG modifications, and these are significantly greater for clozapine and appear dependent on chlorpromazine equivalent dose. No encephalopathy was observed in these antipsychotic monotherapies, whatever dose.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Cerebral Cortex; Clozapine; Depressive Disorder, Major; Electroencephalography; Female; Humans; Male; Mental Disorders; Middle Aged; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Young Adult

Electroconvulsive therapy (ECT) is rarely, if ever, considered for the treatment of severe anorexia nervosa (AN) or other eating disorders comorbid with an affective illness. Mood disorders are common in these patients, and psychotropic medications, although frequently used, have limited evidence of benefit in AN or copresenting depressive symptoms. Even when the illness is life threatening, ECT as a treatment may be overlooked. We present a case of an adolescent girl with severe AN and comorbid major depressive disorder with suicidality. This patient failed multiple medication trials but went on to experience complete remission from both the symptoms of her AN and major depressive disorder after undergoing a course of bilateral ECT. Electroconvulsive therapy may prove to be a fast and effective treatment strategy for mood disorders and suicidality in the setting of comorbid AN in adolescents.

Topics: Adolescent; Anorexia Nervosa; Benzodiazepines; Citalopram; Depressive Disorder, Major; Electroconvulsive Therapy; Female; Humans; Male; Olanzapine; Selective Serotonin Reuptake Inhibitors; Suicide; Treatment Outcome

Topics: Adult; Advance Care Planning; Aged; Antiemetics; Baclofen; Benzodiazepines; Constipation; Depressive Disorder, Major; Dyspnea; Female; Hiccup; Humans; Male; Methylphenidate; Middle Aged; Morphinans; Morphine; Nausea; Olanzapine; Palliative Medicine; Polyethylene Glycols; Prochlorperazine; Pruritus; Sertraline; Terminal Care; Walkers

Major depressive disorder (MDD) is a debilitating psychiatric illness with a high cost burden. This analysis evaluates the cost-effectiveness of adjunctive brexpiprazole versus comparator branded adjunctive treatment for MDD and background antidepressant therapy (ADT) alone from a US payer perspective.. An economic model was developed to assess the cost-effectiveness of brexpiprazole versus comparator adjunctive treatment and ADT alone on total direct medical costs using a 6-week cycle time frame for a total of 48 weeks, with treatment response and remission as primary outcomes. The model consisted of 3 parts, 1 to represent the acute treatment phase and 2 to represent the maintenance stage.. In the base-case analysis, brexpiprazole as reference treatment resulted in cost per additional responder ranging from $19,442-$48,745 and cost per additional remitter ranging from $27,196-$71,839 versus comparator treatments over 48 weeks. Sensitivity analyses showed treatment with brexpiprazole was more costly, but more clinically effective in all probabilistic simulations.. This representation of disease natural history over 48 weeks may not account for all possible health states. Resource utilization on treatment was estimated using the resource use data from previous trials, and may overestimate medical costs compared to the real-world setting. Treatment comparators were limited to branded therapies, and head-to-head studies were not available to obtain data inputs.. Compared to other branded adjunctive therapies, brexpiprazole increases response and remission at 6 weeks; medical care cost savings were observed with the use of brexpiprazole. These findings may assist clinicians and formulary decision makers when selecting treatment for MDD.

Topics: Adolescent; Adult; Aged; Akathisia, Drug-Induced; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Cost-Benefit Analysis; Depressive Disorder, Major; Disorders of Excessive Somnolence; Drug Costs; Drug Therapy, Combination; Fatigue; Female; Health Care Costs; Humans; Male; Middle Aged; Models, Economic; Olanzapine; Patient Selection; Quetiapine Fumarate; Quinolones; Serotonin Agents; Thiophenes; Weight Gain; Young Adult

A recently published analysis of population-based claims data from Ontario, Canada reported higher risks of acute kidney injury (AKI) and related outcomes among older adults who were new users of atypical antipsychotics (AAPs) compared with unexposed patients. In light of these findings, the objective of the current study was to further investigate the risks of AKI and related outcomes among older adults receiving AAPs.. A replication of the previously published analysis was performed using the US Truven MarketScan Medicare Supplemental database (MDCR) among patients aged 65 years and older. Compared with non-users of AAPs, the study compared the risk of AKI and related outcomes with users of AAPs (quetiapine, risperidone, olanzapine, aripiprazole, or paliperidone) using a 1-to-1 propensity score matched analysis. In addition, we performed adapted analyses that: (1) included all covariates used to fit propensity score models in outcome models; and (2) required patients to have a diagnosis of schizophrenia, bipolar disorder, or major depression and a healthcare visit within 90 days prior to the index date.. AKI effect estimates [as odds ratios (ORs) with 95% confidence intervals (CIs)] were significantly elevated in our MDCR replication analyses (OR 1.45, 95% CI 1.32-1.60); however, in adapted analyses, associations were not significant (OR 0.91, 95% CI 0.78-1.07)). In analyses of AKI and related outcomes, results were mostly consistent between the previously published and the MDCR replication analyses. The primary change that attenuated associations in adapted analyses was the requirement for patients to have a mental health condition and a healthcare visit prior to the index date.. The MDCR analysis yielded similar results when the methodology of the previously published analysis was replicated, but, in adapted analyses, we did not find significantly higher risks of AKI and related outcomes. The contrast of results between our replication and adapted analyses may be due to the analytic approach used to compare patients (and potential confounding by indication). Further research is warranted to evaluate these associations, while also examining methods to account for differences in older adults who do and do not use these medications.

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder, Major; Female; Humans; Male; Olanzapine; Quetiapine Fumarate; Risperidone; Schizophrenia

The Psychotic Depression Assessment Scale (PDAS) is a rating scale dedicated to the measurement of severity in psychotic depression (PD). The aim of this study was to establish the PDAS cut-off for remission of PD as well as PDAS score-ranges for mild, moderate, and severe PD. The secondary aim was to test how remission, as defined by the PDAS, would perform as outcome measure when applied to the data from a large randomized controlled trial (RCT) in PD.. The study was based on data from the Study of Pharmacotherapy in Psychotic Depression (STOP-PD). The cut-off for remission on the PDAS and the severity-ranges for mild, moderate, and severe PD were defined using the Clinical Global Impression - Severity scale (CGI-S) as reference by means of pair-wise receiver operating characteristic (ROC) analyses. Subsequently, it was tested whether remission on the PDAS could separate the effects of Olanzapine+Sertraline vs. Olanzapine+Placebo through an intention-to-treat, mixed-effects logistic regression of the data from STOP-PD.. According to the ROC analyses, the ideal cut-off for remission of PD was a PDAS total score <8, while the severity-ranges for mild, moderate and severe PD were 8-15, 16-23, and >23 respectively. When applying the PDAS total score <8 (remission) as outcome on the STOP-PD data, treatment with Olanzapine+Sertraline performed significantly better than Olanzapine+Placebo (p<0.001).. The STOP-PD was not designed specifically to answer the research questions of the present study.. According to this study, a total score <8 on the PDAS corresponds to remission of PD.

Topics: Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Drug Therapy, Combination; Female; Humans; Olanzapine; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic; Remission Induction; ROC Curve; Sertraline; Severity of Illness Index

Topics: Abortion Applicants; Adult; Benzodiazepines; Depressive Disorder, Major; Drug Dosage Calculations; Female; Humans; Olanzapine; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Psychiatric Status Rating Scales; Psychological Techniques; Selective Serotonin Reuptake Inhibitors; Treatment Outcome; Venlafaxine Hydrochloride

We recently reported an unexpected interaction between olanzapine and sertraline in a population being treated for psychotic depression. Contrary to knowledge of cytochrome p450 interactions sertraline increased apparent clearance of olanzapine by 30%. Here we examined the pharmacokinetics of sertraline in the same population. Existing studies suggest that sertraline apparent clearance is significantly increased in male subjects and suggested an age/sex interaction.. We studied subjects undergoing combination of sertraline/olanzapine treatment for psychotic depression in the Study of the Pharmacotherapy of Psychotic Depression. Nonlinear mixed effect modelling software was used to examine the sertraline pharmacokinetics, evaluating age, sex, race, and olanzapine exposure as covariates.. Eighty-seven subjects (median age 62 years, 28 male subjects, 11 African-Americans) provided 138 samples for sertraline concentration. Olanzapine exposure had a 14.8-fold range. A one compartment model with combined residual error described the sertraline concentration data adequately. Half-life and sex effect on sertraline apparent clearance (males averaging 50% higher (p < 0.005); 96.6 l/h vs 64.8 in female subjects) were similar to previous reports. No other covariate (age, race or olanzapine exposure) had a significant impact on apparent clearance, and no age/sex interaction emerged.. Sertraline pharmacokinetics were similar to historical descriptions in populations not taking antipsychotics. Unlike our unexpected finding that sertraline increases olanzapine apparent clearance, olanzapine exposure had no impact on sertraline pharmacokinetics. Copyright © 2016 John Wiley & Sons, Ltd.

Topics: Adult; Age Factors; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Drug Interactions; Drug Therapy, Combination; Female; Half-Life; Humans; Male; Middle Aged; Models, Biological; Nonlinear Dynamics; Olanzapine; Psychotic Disorders; Selective Serotonin Reuptake Inhibitors; Sertraline; Sex Factors

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

A woman in her 60s with a history of hepatitis C with cirrhosis and major depressive disorder with psychotic features was admitted to the inpatient psychiatric unit for suicidal ideation. She was initially treated with a combination of sertraline and paliperidone. The paliperidone was subsequently changed to risperidone and ultimately to olanzapine. She developed worsening mental status and was then treated for catatonia with benzodiazepines. Over 2 days, her mental status continued to worsen and she developed fever and tachycardia. She was transferred to the ICU and endotracheally intubated for inability to protect her airway. She was started on lactulose via orogastric tube but showed no improvement in her mental status after 2 days despite having two or three bowel movements per day.

Topics: Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Diagnosis, Differential; Female; Humans; Intensive Care Units; Middle Aged; Neuroleptic Malignant Syndrome; Olanzapine

Depression is the predominant psychosocial and suicide burden in bipolar disorder, yet there is a paucity of evidence-based treatments for bipolar depression.. This post hoc subgroup analysis of data pooled from two 3-week, randomized, placebo- and olanzapine-controlled trials (December 2004-April 2006, N = 489 and November 2004-April 2006, N = 488) examined a subgroup of patients meeting criteria for moderate-to-severe mixed major depressive episodes, defined using DSM-IV-TR criteria for mixed episodes (mania and major depression simultaneously) with a baseline Montgomery-Asberg Depression Rating Scale (MADRS) total score ≥ 20.. Decreases in MADRS scores (least squares mean [SE]), the a priori primary outcome, were significantly greater in the asenapine group than in the placebo group from baseline to day 7 (-11.02 [1.82] vs -4.78 [1.89]; P = .0195), day 21 (-14.03 [2.01] vs -7.43 [2.09]; P = .0264), and endpoint (-10.71 [1.76] vs -5.19 [1.98]; P = .039). Decreases in MADRS scores with asenapine were significantly greater than with olanzapine from baseline to day 7 (-6.26 [1.47]; P = .0436). Decreases in Young Mania Rating Scale mean total score were greater with asenapine than with placebo or olanzapine at all time points assessed. A significantly greater reduction from baseline to day 21 in the Short Form-36 mental component summary score was observed with asenapine, but not olanzapine, compared with placebo (16.57 vs 5.97; P = .0093). Asenapine was generally well tolerated.. These data provide support for the potential efficacy of asenapine in mixed major depressive episodes; however, these data cannot be linearly extrapolated to nonmixed major depression.

Topics: Adult; Aged; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder, Major; Dibenzocycloheptenes; Double-Blind Method; Female; Heterocyclic Compounds, 4 or More Rings; Humans; Male; Middle Aged; Multicenter Studies as Topic; Olanzapine; Randomized Controlled Trials as Topic; Retrospective Studies; Treatment Outcome; Young Adult

This study aims to investigate the effects of low-dose olanzapine on preventing occurrence and controlling the severity of nausea and vomiting related to duloxetine in treating major depressive disorder.. Two hundred sixty-eight subjects with major depressive disorder were divided into control and trial groups. The control group had 165 subjects and was treated with duloxetine only, whereas the trial group had 103 subjects and received duloxetine combined with low-dose olanzapine. After the treatment for 2 weeks, both groups were evaluated for occurrence and severity of adverse effects on digestive tract using the Treatment Emergent Symptom Scale.. The trial group, scored at 13, showed significantly less occurrence and severity of nausea and vomiting than the control group, scored at 38 (P < 0.05). The occurrence of nausea and vomiting in the trial group is significantly lower compared with that in the control group, and the occurrence decreases as the dose of olanzapine increases (P < 0.05). The antiemetic effect of olanzapine is valid to all subjects who received it.. Duloxetine combined with low-dose olanzapine can effectively reduce the occurrence and severity of duloxetine-related nausea and vomiting. With the increase of olanzapine dose, the antiemetic effect becomes stronger. Olanzapine is a safe and efficient drug for the prevention of duloxetine-related nausea and vomiting.

Topics: Adolescent; Adult; Antidepressive Agents; Antiemetics; Benzodiazepines; Depressive Disorder, Major; Drug Administration Schedule; Drug Therapy, Combination; Duloxetine Hydrochloride; Female; Humans; Male; Middle Aged; Nausea; Olanzapine; Thiophenes; Treatment Outcome; Vomiting; Young Adult

Use of electroconvulsive therapy (ECT) has been infrequently described in patients with systemic lupus erythematosus and is most commonly used in patients with catatonia. In this report, we describe the use of ECT in a young adolescent girl who had bipolar affective disorder associated with systemic lupus erythematosus and was treated with ECT for the depressive episode. The patient achieved remission with a course of 6 ECT treatments.

Topics: Adolescent; Alkylating Agents; Anti-Inflammatory Agents; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cyclohexanols; Cyclophosphamide; Depressive Disorder, Major; Electroconvulsive Therapy; Female; Humans; Lupus Erythematosus, Systemic; Olanzapine; Prednisolone; Venlafaxine Hydrochloride

To evaluate the effectiveness and safety of maintenance electroconvulsive therapy (mECT) in elderly patients with treatment-resistant Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition major depressive episode.. Seven elderly patients with treatment-resistant major depressive episode were treated with a complete ECT cycle. Thereafter, they received one monthly ECT session as maintenance for 1 year. Response to treatment was defined as at least a 50% drop from baseline on the Hamilton Depression Rating Scale (HamD) and remission as not meeting criteria for major depression, a HamD score of 7 or less, and Clinical Global Impressions-Severity of Illness score of 1. We compared their response with the response of 7 elderly patients with treatment-resistant major depression who were treated with a full cycle of ECT but did not receive mECT (non-mECT). We compared the 2 groups for the number of relapses or recurrences of major depressive episodes after remission was achieved; a relapse or a recurrence occurred when HamD scores were 14 or higher, or when Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision major depressive episode criteria were met, or when Clinical Global Impressions-Severity of Illness score was 3 or higher and increased by at least 2 points from response/remission.. The mECT group (4 women and 3 men; mean age, 73 years) had significantly less mean relapses/recurrences (0 vs 1.57) and hospitalizations (0 vs 1) and received less drug treatment than the nonMECT group (similar for age and sex composition) during the 12-month follow-up period. All patients with mECT improved during treatment and did not relapse.. Maintenance ECT protected elderly patients from recurrent depressive episodes from relapsing/recurring more than standard ECT.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Electroconvulsive Therapy; Female; Hospitalization; Humans; Male; Olanzapine; Psychiatric Status Rating Scales; Secondary Prevention; Severity of Illness Index; Treatment Outcome

Depression is a disorder held responsible for high morbidity in the overall population. Causes of depression vary, but lifestyle and stress can greatly contribute to its morbidity. Consumption of antidepressants is showing a trend in the economically developed countries. Apart from antidepressants, the treatment of depression can consist of other psychopharmaca. Depending on the severity of a disorder, that is - of psychotic symptoms, antipsychotics can be introduced in the treatment. Among those atypical antipsychotics have an advantage. This paper will illustrate a course of treatment of a female patient, diagnosed with psychotic depression and treated with antipsychotics (i.e. olanzapine, ziprasidone), to which she developed side effects. To each of the antypsychotics the patient developed side effechts, causing in prolonged treatment and affected its course.

Topics: Affective Disorders, Psychotic; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Dose-Response Relationship, Drug; Drug Eruptions; Drug Substitution; Drug Therapy, Combination; Female; Humans; Middle Aged; Olanzapine; Piperazines; Pruritus; Sulpiride; Thiazoles; Weight Gain

The following case report describes an act of genital self mutilation. An employed, unmarried male suffering from schizophrenia paranoid type, autocastrated his genitalia during a period of illness when his psychotic symptoms were absent. Sufficient attention may not have been paid to his depressive symptomatology which may be primary as a core feature or secondary, in what can be called post-psychotic depression. The vulnerability of committing such an act increases when the person appears to be symptom-free and regaining insight. After a review of the available literature, it is considered that this case best fits the description for Klingsor Syndrome.

Topics: Adult; Antipsychotic Agents; Awareness; Benzodiazepines; Depressive Disorder, Major; Humans; Male; Olanzapine; Orchiectomy; Penis; Psychiatric Status Rating Scales; Schizophrenia, Paranoid; Scrotum; Self Mutilation; Syndrome

We report about a woman of 60 years who received psychiatric inpatient treatment for an affective disorder with psychotic symptoms on several occasions. As time elapsed symptoms of dementia became more and more obvious. Despite a comprehensive workup with neuroimaging methods (SPECT, PET) the correct diagnosis of Huntington's Chorea was not attained until the characteristic movements appeared. Up till then pathologic movements had hardly occurred and there were no known cases of Huntington's Chorea in the family. This case is remarkable as the patient was not only treated with different antidepressants and antipsychotics but with a course of ECT too. Beyond this it shows the enormous stress this illness imposes on patients and their caregivers.

Topics: Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Brain; Combined Modality Therapy; Dementia; Depressive Disorder, Major; Diagnosis, Differential; Disease Progression; Electroconvulsive Therapy; Female; Humans; Huntington Disease; Middle Aged; Olanzapine; Positron-Emission Tomography; Psychotic Disorders; Suicidal Ideation; Tomography, Emission-Computed, Single-Photon; Treatment Failure

Olanzapine augmentation of fluoxetine, a selective serotonin reuptake inhibitor, is an effective augmentation therapy for treatment-resistant depression (TRD). However, studies of olanzapine augmentation of other antidepressants are few. We investigated the efficacy and safety of olanzapine augmentation of milnacipran, a serotonin-norepinephrine reuptake inhibitor, for TRD.. This study covered patients with stage 2 TRD, defined by Thase and Rush. Olanzapine was added to milnacipran, and its dosage was adjusted according to each patient. Previous treatments were continued, but no new treatments were allowed. Response was measured using Hamilton Depression Rating Scale (HAMD) and Clinical Global Impression at weeks 0, 1, 2, 3, 4, and 8.. Eleven patients aged 53.2 ± 24.0 years received olanzapine at 5.0 ± 1.9 mg/day with milnacipran. HAMD and Clinical Global Impression scores improved significantly from baseline to endpoint. This improvement occurred in week 1. At endpoint, seven of 11 (64%) were responders on HAMD (≥ 50% reduction). Four patients (36%) discontinued the trial because of no efficacy. No severe adverse effect occurred.. Olanzapine augmentation of milnacipran for stage 2 TRD might be effective and well tolerated. However, our study is open label and uncontrolled. Therefore, a double-blind controlled trial is necessary to confirm our results.

Topics: Adolescent; Adult; Aged; Benzodiazepines; Cyclopropanes; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Drug Synergism; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Milnacipran; Olanzapine; Young Adult

To compare health care utilization and expenditures in patients with depression whose initial antidepressant (AD) treatment was augmented with a second-generation antipsychotic.. Claims data from January 1, 2001, through June 30, 2009, were used to select patients aged 18 to 64 years with depression treated with ADs augmented with aripiprazole, olanzapine, or quetiapine. Patients were required to have 6 months of continuous eligibility before the first AD prescription and 6 months after the second-generation antipsychotic augmentation (index) date. Utilization and expenditures were assessed for 6 months after the index date. Multivariate regression was used to estimate adjusted expenditures and risks for hospitalizations and emergency department visits.. A total of 483 patients treated with aripiprazole, 978 with olanzapine, and 2471 with quetiapine were selected. Mean adjusted expenditures for aripiprazole were significantly lower than those for olanzapine for each service category (all-cause, all-cause medical care, mental health-related, and mental health-related medical care) and were significantly lower than those for quetiapine for each category with the exception of mental health-related. The adjusted risks for hospitalization and emergency department visits were significantly higher for quetiapine than for aripiprazole.. Compared with patients treated with ADs and aripiprazole, those treated with ADs and olanzapine or quetiapine had greater utilization and higher expenditures.

Topics: Adolescent; Adult; Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Data Interpretation, Statistical; Databases, Factual; Depressive Disorder, Major; Dibenzothiazepines; Drug Costs; Drug Therapy, Combination; Drug Utilization Review; Female; Health Expenditures; Humans; Insurance Claim Review; Male; Middle Aged; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Young Adult

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Depressive Disorder, Major; Dibenzothiazepines; Drug Approval; Drug Therapy, Combination; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risperidone; United States; United States Food and Drug Administration

To identify the factors associated with newly prescribed, first-line, second-generation antipsychotics (SgAs) associated with weight gain-olanzapine, risperidone, and quetiapine.. Retrospective medical record review.. Outpatient and inpatient psychiatry services at a tertiary care, academic medical center.. Three hundred forty consecutive adults who had major depressive disorder with psychotic features, bipolar I, bipolar II, bipolar not otherwise specified, or schizoaffective disorder over two time periods (August 30-October 30, 2009, and April 1-May 31, 2010).. Clinical and sociodemographic variables associated with newly prescribed olanzapine, risperidone, and quetiapine were identified by using univariate and multivariate logistic regression. Several clinical factors were individually associated with initiation of these SgAs: mania (odds ratio [OR] 3.6, 95% confidence interval [CI] 1.2-10.8, p=0.02), psychosis (OR 3.3, 95% CI 1.5-6.9, p=0.002), and inpatient treatment (OR 3.8, 95% CI 1.8-7.9, p=0.0005). Prevalent use of lithium (OR 0.3, 95% CI 0.1-0.9, p=0.03) and being married (OR 0.3, 95% CI 0.1-0.8, p=0.02) were inversely associated with new use of an SgA. Mania, psychosis, married status, and lithium use remained independently associated on multivariate analysis. Factors related to metabolic or vascular risk were not associated with SgA initiation.. Psychiatric clinicians were influenced heavily by clinical features related to mental status and acuity when determining whether to prescribe SgAs. However, factors related to vascular risk were not associated. Future observational studies should consider current clinical status as an important factor in determining propensity to receive antipsychotics or other short-term treatments for bipolar and related disorders.

Topics: Academic Medical Centers; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder, Major; Dibenzothiazepines; Female; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Olanzapine; Practice Patterns, Physicians'; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risperidone; Weight Gain

Mefloquine (Lariam) is the drug of choice as malaria prophylaxis for travel to chloroquine-resistant areas. Severe neuropsychiatric side effects are rare. We report two clinical cases of mood disorders: mania and a major depressive episode with psychotic characteristics in two patients with mefloquine antimalarial prophylaxis. FIRST CLINICAL CASE: A 31-year-old man had taken mefloquine at a rate of 250mg/week as malaria prophylaxis for his mission in Democratic Republic of Congo. He developed mania with psychotic symptoms after taking five tablets of 250mg of mefloquine. He exhibited an elevated mood and also developed delusions of grandeur, reference and persecution, with auditory hallucinations. The physical examination and the blood laboratory tests were normal. The patient was treated with an atypical neuroleptic (olanzapine 20mg/d) leading to a complete resolution of symptomatology at the end of 3 weeks. SECOND CLINICAL CASE: A 27-year-old man presented a major depressive episode with psychotic symptoms after 1 week on his return from a stay in Democratic Republic of Congo, where he had taken mefloquine during 6 months as malaria prophylaxis (250mg/week). His physical examination and investigations (full blood test, serology and MRN) were normal. The patient was treated with clomipramine (150mg/d) and olanzapine (20mg/d). The outcome was favorable after 4 weeks.. Mefloquine is widely accepted as a safe and effective treatment and a prophylactic agent for chlorquine-resistant malaria. Common neuropsychiatric adverse effects of mefloquine can occur in up to 40% of patients, such as dizziness, sleep disturbances, anorexia, ataxia, and fatigue. Other more serious adverse reactions are rare. They are represented primarily by panic attacks, convulsions, acute psychosis, paranoid delusions, suicidal ideation, disorders of mood: major depressive episode and the manic excitation. The incidence of such neuropsychiatric effects is 1/10,000 to 1/15,000 during the prophylactic treatment. The causal mechanism for the side effects is not known. Several risk factors increasing the neurotoxicity of mefloquine can be identified, the patient with personal or family history of psychiatric disorders are more frequently concerned. Alcohol and the association with other drugs (like quinine) are two other risk factors.. It is relevant for medical practitioners to be aware of the severe neuropsychiatric side effects of mefloquine as malaria prophylaxis. It requires investigation of the risk factors such as personal or family history of psychiatric disorders.

Topics: Adult; Antimalarials; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clomipramine; Depressive Disorder, Major; Drug Therapy, Combination; Humans; Malaria; Male; Mefloquine; Olanzapine; Psychoses, Substance-Induced

Topics: Antipsychotic Agents; Benzodiazepines; Catatonia; Child; Depressive Disorder, Major; Female; Follow-Up Studies; Humans; Olanzapine; Remission Induction

To evaluate the efficacy of olanzapine/fluoxetine combination (OFC) versus olanzapine or fluoxetine monotherapy across all clinical trials of treatment-resistant depression sponsored by Eli Lilly and Company.. Efficacy and safety data from 1146 patients with a history of nonresponse during the current depressive episode who subsequently exhibited nonresponse during a 6- to 8-week antidepressant open-label lead-in phase and were randomly assigned to OFC (N = 462), fluoxetine (N = 342), or olanzapine (N = 342) for double-blind treatment were analyzed. All patients had a diagnosis of major depressive disorder as defined by DSM-III or DSM-IV criteria. The dates in which the trials were conducted ranged from May 1997 to July 2005.. After 8 weeks, OFC patients demonstrated significantly greater Montgomery-Asberg Depression Rating Scale improvement (mean change = -13.0) than fluoxetine (-8.6, p < .001) or olanzapine (-8.2, p < .001) patients, via a mixed-effects model repeated-measures analysis. Remission rates were 25.5% for OFC, 17.3% (p = .006) for fluoxetine, and 14.0% (p < .001) for olanzapine. Adverse events in >or= 10% of OFC patients were weight gain, increased appetite, dry mouth, somnolence, fatigue, headache, and peripheral edema. Random glucose mean change (mg/dL) was +7.92 for the OFC group, +1.62 for the fluoxetine group (p = .020), and +9.91 for the olanzapine group (p = .485). Random cholesterol mean change (mg/dL) was +12.4 for OFC, +2.3 for fluoxetine (p < .001), and +3.1 for olanzapine (p < .001); incidence of treatment-emergent increase from normal to high cholesterol (baseline < 200 mg/dL and >or= 240 subsequently) was significantly higher for the OFC group (10.2%) than for the fluoxetine group (3.1%, p = .017) but not the olanzapine group (8.0%, p = .569). Mean weight change (kg) was +4.42 for OFC, -0.15 for fluoxetine (p < .001), and +4.63 for olanzapine (p = .381), with 40.4% of OFC patients gaining >or= 7% body weight (vs. olanzapine: 42.9%, p = .515; fluoxetine: 2.3%, p < .001).. Results of this analysis showed that OFC-treated patients experienced significantly improved depressive symptoms compared with olanzapine- or fluoxetine-treated patients following failure of 2 or more antidepressants within the current depressive episode. Safety results for OFC were generally consistent with those for its component monotherapies. The total cholesterol increase associated with OFC was more pronounced than with olanzapine alone.

Topics: Adult; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Benzodiazepines; Cyclohexanols; Depressive Disorder, Major; Double-Blind Method; Drug Resistance; Drug Therapy, Combination; Female; Fluoxetine; Humans; Male; Middle Aged; Nortriptyline; Olanzapine; Personality Inventory; Psychometrics; Randomized Controlled Trials as Topic; Treatment Outcome; Venlafaxine Hydrochloride

Topics: Anti-Inflammatory Agents; Antidepressive Agents, Tricyclic; Antipsychotic Agents; Ataxia; Benzodiazepines; Depressive Disorder, Major; Doxepin; Female; Humans; Middle Aged; Olanzapine; Opioid-Related Disorders; Prednisone; Psychotic Disorders; Treatment Outcome; Vasculitis, Central Nervous System

Mixed depression (ie, co-occurrence of syndromal depression and subsyndromal mania/hypomania) is a common variant of bipolar depression. However, its treatment is much understudied. The aim of the study was to assess the efficacy of the antipsychotic and mood-stabilizing agent olanzapine and the efficacy of the combination of an antidepressant (fluoxetine) and olanzapine (olanzapine/fluoxetine combination; OFC) for the treatment of bipolar I mixed depression.. We carried out a post hoc analysis of an 8-week, double-blind trial of adult bipolar I depression treated with placebo (n = 355), olanzapine (5-20 mg/d; n = 351), or OFC (olanzapine/fluoxetine doses: 6/25, 6/50, 12/50 mg/d; n = 82). Studying mixed depression was not a previous goal of the double-blind trial. Subjects in the trial were diagnosed according to DSM-IV and were randomly assigned to treatment during the period June 2000 to December 2001. Mixed depression was defined as the co-occurrence of a major depressive episode and > or = 2 manic/hypomanic symptoms (ie, > or = 2 Young Mania Rating Scale [YMRS] items scoring > or = 2). Response was defined as a > or = 50% reduction in Montgomery-Asberg Depression Rating Scale score and < 2 concurrent manic/hypomanic symptoms. Switching to mania/hypomania was defined as a YMRS score > or = 15.. Frequency of mixed depression was 45.1% in the OFC arm, 49.3% in the olanzapine arm, and 46.8% in the placebo arm (P = .705). The most frequent manic/ hypomanic symptoms of mixed depression were irritability, reduced need for sleep, talkativeness, and racing thoughts. Response rates in patients with nonmixed depression versus patients with mixed depression were the following: in the OFC arm, 48.9% versus 43.2% (OR = 1.24; 95% CI, 0.51-2.98); in the olanzapine arm, 39.9% versus 26.6% (OR = 1.84; 95% CI, 1.17-2.90); in the placebo arm, 27.5% versus 16.3% (OR = 1.94; 95% CI, 1.15-3.28). Response rates in the samples of patients with mixed depression were the following: OFC versus olanzapine, OR = 2.00 (95% CI, 0.96-4.19); OFC versus placebo, OR = 3.91 (95% CI, 1.80-8.49); olanzapine versus placebo, OR = 1.95 (95% CI, 1.14-3.34). It was found that no baseline manic/hypomanic symptom of mixed depression predicted treatment response. A higher number of baseline concurrent manic/hypomanic symptoms predicted a lower response rate in the olanzapine and placebo arms, but not in the OFC arm. The rates of switching were the following: in the OFC arm, 8.5%; in the olanzapine arm, 6.8%; and in the placebo arm, 7.9% (P = .808). The rates of dropouts in patients with mixed depression versus patients with nonmixed depression were not significantly different within any of the treatment arms. The rates of dropouts in the samples of patients with mixed depression were the following: in the OFC arm, 29.7%; in the olanzapine arm, 53.8%; and in the placebo arm, 59.6% (olanzapine vs OFC: OR = 2.66; 95% CI, 1.23-5.75; placebo vs OFC: OR = 3.48; 95% CI, 1.61-7.54; placebo vs olanzapine: OR = 1.30; 95% CI, 0.84-2.01).. Olanzapine/fluoxetine combination may be an effective treatment for bipolar I mixed depression. Statistically, the efficacy of OFC was not significantly different from that of olanzapine, but inspection of the 95% CI showed a trend in favor of a possible superiority of OFC. Supporting the study findings are the similar efficacy of OFC in bipolar mixed depression independent of the number of concurrent manic/hypomanic symptoms, a lower dropout rate, and a similarly low switching rate compared to olanzapine. Contrary to other current limited evidence, an antidepressant (fluoxetine) showed efficacy and did not worsen bipolar mixed depression if combined with a mood-stabilizing agent (olanzapine).

Topics: Adult; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Comorbidity; Depressive Disorder, Major; Drug Therapy, Combination; Female; Fluoxetine; Humans; Male; Olanzapine; Placebos; Randomized Controlled Trials as Topic; Risperidone; Treatment Outcome

We report the case of two young subjects who developed an obsessive-compulsive disorder (OCD) during a heavy use of ecstasy. After several months of discontinuation of the drug, major depression with psychotic features developed in one subject and a psychotic disorder in the other individual. No mental disorder preceded the use of ecstasy in any subject.. A familial and personality vulnerability for mental disorder was revealed in one subject, but not in the other, and all physical, laboratory and cerebral NMR evaluations showed normal results in both patients. Remission of OCD and depressive episode or psychotic disorder was achieved after treatment with a serotoninergic medication associated with an antipsychotic.. The heavy long-term use of ecstasy may induce an alteration in the brain balance between serotonin and dopamine, which might constitute a pathophysiological mechanism underlying the onset of obsessive-compulsive, depressive and psychotic symptoms. The heavy use of ecstasy probably interacted with a vulnerability to psychiatric disorder in one subject, whereas we cannot exclude that an "ecstasy disorder" ex novo affected the other individual.

Topics: Adolescent; Amphetamine-Related Disorders; Antidepressive Agents, Tricyclic; Antipsychotic Agents; Benzodiazepines; Borderline Personality Disorder; Brain; Clomipramine; Comorbidity; Depressive Disorder, Major; Dopamine; Female; Genetic Predisposition to Disease; Hallucinogens; Humans; Male; N-Methyl-3,4-methylenedioxyamphetamine; Obsessive-Compulsive Disorder; Olanzapine; Psychoses, Substance-Induced; Risk Factors; Risperidone; Serotonin; Substance Withdrawal Syndrome; Young Adult

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Drug Overdose; Female; Humans; Olanzapine; Risk Factors; Suicide, Attempted

Hyperprolactinemia is a frequent side-effect in the use of atypical antipsychotics. The propensity to induce hyperprolactinemia is highly substance dependent and hyperprolactinemia is not always associated with clinical side-effects. We report a case in which hyperprolactinemia and amenorrhea under the treatment with olanzapine gets normalized after the addition of aripiprazole.

Topics: Adult; Amenorrhea; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Drug Interactions; Drug Therapy, Combination; Female; Humans; Hyperprolactinemia; Olanzapine; Piperazines; Quinolones

Several studies have shown that olanzapine is effective in weight restoration and maintenance for patients with anorexia nervosa (AN). However, major depression is a very common comorbid psychiatric disorder associated with AN. Additional antidepressant therapy may be required for treating anorexic patients with major depression. The authors present a case of AN associated with major depression, who responded well to the combination treatment of olanzapine and mirtazapine. A 27-year-old Taiwanese woman was admitted because of severe weight loss, poor nutrition, amenorrhea, major depression, and starvation complications including hematological dyscrasis, electrolytes and endocrine imbalance, and sinus bradycardia. In additional to nutritional and medical treatments, the patient was given olanzapine 10 mg/day and mirtazapine 30 mg/day. She took the combined medications for six months. Meanwhile she received cognitive behavior therapy and family therapy. With these treatments, the patient's depression was in remission, her body weight was increased from 24 to 38 kg, and her body mass index was increased from 9.8 to 15.5. Our case suggests that the combined treatment of olanzapine and mirtazapine can be used in the treatment of AN associated with major depression.

Topics: Adult; Anorexia Nervosa; Antidepressive Agents, Tricyclic; Antiemetics; Benzodiazepines; Depressive Disorder, Major; Drug Therapy, Combination; Female; Humans; Mianserin; Mirtazapine; Olanzapine

Massive elevations of serum creatine kinase (CK) can occur in a significant number of patients treated with neuroleptics in the absence of neuroleptic malignant syndrome (NMS). We report two cases of CK-elevations associated with quetiapine treatment, which disappeared after drug discontinuation. To our knowledge, case number one is the first case of quetiapine-induced CK elevation in a neuroleptic-naïve patient. We thus suggest CK assessment when myalgia occurs with neuroleptic treatment.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Clozapine; Creatine Kinase; Depressive Disorder, Major; Dibenzothiazepines; Humans; Male; Mianserin; Mirtazapine; Olanzapine; Pain; Psychotic Disorders; Quetiapine Fumarate

Over two thirds of people suffering from depression complain of pain with or without reporting psychological symptoms. Physical symptoms are more prevalent among the women, the elderly, the poor, and in children population. Successful treatment of depression in children complicated by pain symptoms constitutes a great clinical challenge. Duloxetine has already emerged as a safe and effective treatment option for adult depressed patients with painful physical symptoms. However, no data exist in literature which suggests use of duloxetine in childhood and adolescent population for the same clinical indication. We report a case documenting successful use of duloxetine in a depressed girl child who also had severe pain and dissociative symptoms.

Topics: Antidepressive Agents; Benzodiazepines; Child; Depressive Disorder, Major; Dissociative Disorders; Duloxetine Hydrochloride; Female; Humans; Olanzapine; Pain; Thiophenes

A 38-year-old woman with medication-resistant major depression and posttraumatic stress disorder was treated with electroconvulsive therapy (ECT) concurrent with a duloxetine-olanzapine combination. The treatment resulted in complete resolution of major depression without any complications. This case report suggests that treatment with the combination of duloxetine and olanzapine concurrently with ECT was found safe and uncomplicated. The literature on the combined use of antidepressants and ECT is briefly reviewed.

Topics: Adult; Benzodiazepines; Combined Modality Therapy; Depressive Disorder, Major; Duloxetine Hydrochloride; Electroconvulsive Therapy; Female; Humans; Olanzapine; Selective Serotonin Reuptake Inhibitors; Stress Disorders, Post-Traumatic; Thiophenes

The atypical antipsychotic drug olanzapine has been employed as an augmentation treatment in depressed patients unresponsive to treatment with selective serotonin reuptake inhibitors (SSRIs). In healthy subjects, acute olanzapine administration increases sleep continuity and enhances slow wave sleep (SWS). The aim of the present study was to determine if the addition of olanzapine to SSRI treatment in depressed patients produced similar effects on sleep.. We measured the effect of open-label olanzapine addition (2.5 mg/day initially) on the polysomnograms of 12 patients referred from primary care sources who met DSM-IV criteria for major depressive disorder and who had had an unsatisfactory response to therapeutic doses of an SSRI. Patients were first enrolled in November 2001; final assessment occurred in November 2003. Sleep polysomnogram recordings were made on 3 occasions: before olanzapine addition, on the first night of olanzapine treatment, and after 3 weeks of olanzapine treatment.. After the first night of olanzapine treatment and during the third week, subjects showed improvements in sleep efficiency (p < .001), subjective sleep quality (p < .05), and SWS (p < .01). Scores on the Hamilton Rating Scale for Depression fell significantly (p = .001), with the majority of the decrease being apparent after the first week of treatment.. Olanzapine improves sleep continuity and increases SWS in patients receiving SSRI treatment. These effects are apparent after the first dose of olanzapine and are maintained for the next 3 weeks. The ability of olanzapine to increase SWS is probably attributable to 5-HT(2A/2C) receptor blockade, which has been identified as a relevant mechanism in the therapeutic effect of olanzapine in SSRI-resistant depressed patients.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Dose-Response Relationship, Drug; Drug Resistance; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Olanzapine; Polysomnography; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Sleep; Sleep Stages; Treatment Outcome

Topics: Adult; Alcoholism; Antipsychotic Agents; Benzodiazepines; Citalopram; Delusions; Depressive Disorder, Major; Diagnosis, Differential; Drug Therapy, Combination; Hospitalization; Humans; Male; Marijuana Abuse; Olanzapine; Patient Readmission; Psychotic Disorders; Spouses

Atypical antipsychotics, including olanzapine, were originally expected to reduce the risk of haematological toxicity and to be safe alternatives to clozapine. We report a case of patient who developed leucopenia and neutropenia during treatment with olanzapine.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Humans; Leukopenia; Male; Neutropenia; Olanzapine

Topics: Antidepressive Agents, Second-Generation; Antipsychotic Agents; Benzodiazepines; Cyclohexanols; Depressive Disorder, Major; Drug Interactions; Drug Therapy, Combination; Humans; Olanzapine; Venlafaxine Hydrochloride

Topics: Affective Disorders, Psychotic; Aged; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Citalopram; Delusions; Depersonalization; Depressive Disorder, Major; Drug Therapy, Combination; Duloxetine Hydrochloride; Female; Humans; Long-Term Care; Olanzapine; Risperidone; Syndrome; Thiophenes

Topics: Antidepressive Agents; Antipsychotic Agents; Azabicyclo Compounds; Benzodiazepines; Clonazepam; Cyclohexanols; Depressive Disorder, Major; Drug Therapy, Combination; Humans; Hypnotics and Sedatives; Love; Olanzapine; Piperazines; Psychotic Disorders; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride; Wit and Humor as Topic

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Dibenzothiazepines; Female; Fluvoxamine; Humans; Olanzapine; Quetiapine Fumarate; Weight Gain

The emergence or exacerbation of obsessive-compulsive (OC) symptoms during treatment with atypical antipsychotics, mostly clozapine, has been documented by numerous case reports (reviewed by Lykouras et al., 2003). In six recent reports involving nine cases, (Jonkers and de Haan, 2002; Lykouras et al., 2003) olanzapine was found either to cause de novo emergence or to exacerbate OC symptoms. In six of these cases olanzapine caused exacerbation and in three cases caused de novo emergence of OC symptoms.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder, Major; Double-Blind Method; Female; Humans; Obsessive-Compulsive Disorder; Olanzapine; Schizophrenia

Topics: Benzodiazepines; Citalopram; Combined Modality Therapy; Delusions; Depressive Disorder, Major; Electroconvulsive Therapy; Female; Humans; Middle Aged; Olanzapine; Syndrome

Antipsychotic medications are increasingly used in adolescents for a variety of psychiatric difficulties, including psychosis, bipolar disorder, and aggression. Weight gain is a significant side effect of neuroleptics, which may limit adolescents' compliance with these medications. This report presents a case of significant weight loss while on olanzapine, with a body mass index (BMI) falling from 25 to 19.5 during 8 months of treatment. Possible mechanisms for this effect are discussed.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Child; Child Abuse, Sexual; Depressive Disorder, Major; Humans; Male; Obsessive-Compulsive Disorder; Olanzapine; Weight Loss

Topics: Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Drug Resistance; Female; Humans; Middle Aged; Olanzapine; Panic Disorder; Pirenzepine; Psychiatric Status Rating Scales

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Chronic Disease; Depressive Disorder, Major; Dose-Response Relationship, Drug; Drug Resistance; Drug Therapy, Combination; Fluoxetine; Humans; Male; Olanzapine; Pirenzepine

Elevations in prolactin plasma concentration occur with antipsychotics due to their dopamine D2 receptor antagonism. Hyperprolactinemia may be associated with both acute (galactorrhea, amenorrhea, decreased libido etc.) and chronic (predisposition to osteoporosis and cardiovascular disease) treatment emergent effects in both men and women associated with apparently impaired compliance. The aim of our study was to investigate these supposed effects regarding clinically relevant endocrinologic symptoms under routine treatment conditions with newer, atypical antipsychotics. Our findings confirm that amisulpride frequently leads to a remarkable elevation of prolactin plasma concentration, same--in minor degree--for risperidone. Under treatment with quetiapine and olanzapine just temporary elevated prolactin levels were registered. However, no correlation between prolactin levels and dosage could be found. In females treated with amisulpride acute hormonal side effects were seen in a clinically relevant manner. Features of illness itself, stress factors, concomitant medication or other patient's conditions are supposed to be relevant factors for acute endocrine symptomatology.

Topics: Adult; Amisulpride; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Dibenzothiazepines; Female; Humans; Hyperprolactinemia; Male; Middle Aged; Olanzapine; Pirenzepine; Product Surveillance, Postmarketing; Prolactin; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Sulpiride

Individuals with treatment-resistant depression (TRD) utilize more health care services and are significantly more costly. Drug treatments for TRD may include concomitant administration of multiple antidepressants or augmentation with mood stabilizers or antipsychotic agents. An augmentation strategy currently under investigation is the use of an olanzapine plus fluoxetine combination (OFC) therapy. The objectives for this pilot study were to use claims data to: (1) describe the extent of current use of OFC in patients with depressive disorders, and (2) compare health care utilization patterns and medical costs of patients receiving fluoxetine therapy before and after the initiation of olanzapine treatment. Data source consisted of medical, pharmaceutical, and disability claims from a Fortune 100 manufacturer from 1996 to 1998 (N>100,000). The sample included individuals with medical or disability claims for major depressive disorders treated with OFC (nOFC=36). Resource utilization and costs were compared for fluoxetine patients before and after the initiation of olanzapine treatment. Eleven percent of patients on combination therapy received olanzapine and fluoxetine. For patients on fluoxetine, there was a statistically significant reduction in health care utilization, and overall medical costs (20%), following initiation of olanzapine therapy. Overall, it appears the addition of olanzapine to ongoing fluoxetine therapy is effective in reducing outpatient, office, and inpatient utilization, as well as medical costs of patients treated for depression. Further research is needed to investigate combination therapy more fully.

Topics: Adolescent; Adult; Aged; Benzodiazepines; Cost-Benefit Analysis; Depressive Disorder, Major; Drug Therapy, Combination; Female; Fluoxetine; Humans; Male; Mental Health Services; Middle Aged; Olanzapine; Pilot Projects; Selective Serotonin Reuptake Inhibitors; United States

Tardive dyskinesia is a severe complication of neuroleptic treatment. It may develop weeks, even years after starting a neuroleptic treatment and the symptoms may be irreversible. Neuroleptic compounds are not only used in cases of schizophrenia, but also in cases of severe depression with delusional symptoms. We want to present the case of a 67 year old female patient who developed haloperidol induced dyskinesea and stress unto the successful treatment of this complication with olanzapine in combination with paroxetine. Under this regime not only the improvement of the depression, but also of the tardive dyskinesea was impressive.

Topics: Affective Disorders, Psychotic; Aged; Benzodiazepines; Depressive Disorder, Major; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Haloperidol; Humans; Neurologic Examination; Olanzapine; Paroxetine; Patient Admission; Pirenzepine

Topics: Benzodiazepines; Depressive Disorder, Major; Double-Blind Method; Drug Therapy, Combination; Fluoxetine; Humans; Metabolic Clearance Rate; Olanzapine; Pirenzepine; Randomized Controlled Trials as Topic; Treatment Outcome

Topics: Antidepressive Agents, Tricyclic; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Drug Interactions; Drug Therapy, Combination; Humans; Male; Mianserin; Middle Aged; Mirtazapine; Olanzapine; Pirenzepine; Schizophrenia; Schizotypal Personality Disorder; Serotonin Syndrome; Tramadol

Behavioral/psychological symptoms of dementia (BPSD) affect caregiver burden and transition from home to hospital or long-term care. The authors examined change in BPSD for dementia patients (from hospital admission to discharge) who were prescribed haloperidol (n= 289), olanzapine (n=209), or risperidone (n=500). Olanzapine was associated with significantly greater overall improvement in BPSD (based on the Psychogeriatric Dependency Rating Scale total score) than risperidone or haloperidol. Olanzapine was significantly superior on measures of active-, verbal-, and passive-aggression and delusions/hallucinations to risperidone or haloperidol, and, on manipulative behavior and noisiness, to risperidone. Results support the effectiveness of olanzapine in improving several BPSD in hospitalized dementia patients.

Topics: Aged; Aged, 80 and over; Aggression; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Female; Hallucinations; Hospitalization; Humans; Male; Mental Disorders; Middle Aged; Olanzapine; Pirenzepine; Severity of Illness Index; Treatment Outcome

Converging evidence indicates that, in controlled drug trials, individuals receiving novel antipsychotic medications have fewer adverse effects than those receiving conventional antipsychotic medications. This in turn may lead to greater patient treatment satisfaction. This study examines patient satisfaction and burden of adverse effects in a county-wide epidemiologic study of first admission psychotic persons with psychosis who were receiving novel antipsychotic drugs (n = 42). Comparisons were made within this group, and between 25 of these persons and 25 others with the same diagnosis and sex, from the same epidemiologic study, who were receiving a comparable regimen of conventional antipsychotic drugs. Patients receiving novel antipsychotics were significantly more satisfied and were significantly less burdened by adverse effects than those receiving conventional antipsychotics. Among the group receiving novel antipsychotics, dosage was not related to satisfaction or burden of adverse effects. For those treated with risperidone (n = 27), there was a difference, approaching statistical significance, for greater satisfaction and less adverse effect burden among those persons with dosages less than 5 mg daily as compared to higher dosages.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Depressive Disorder, Major; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Neurologic Examination; Olanzapine; Patient Satisfaction; Pirenzepine; Risperidone; Schizophrenia; Schizophrenic Psychology

Four days after swallowing lithium and amitriptyline tablets with suicidal intent, a 48-year-old man was admitted. He was known to be suffering from recurrent depression which had led to 7 previous hospital admissions. At psychiatric assessment he appeared to be depressed with reduced ability of affective changes and impaired formal reasoning. He exhibited delusions of guilt and reference. His sleep was impaired and appetite diminished.. Serum lithium level was 1.98 mmol/l (therapeutic range 0.8-1.0 mmol/l). An ECG demonstrated sinus tachycardia, the EEG showed theta waves with mild general changes.. He was diagnosed as suffering from severe depressive syndrome with psychotic symptoms. He was given both antidepressive and neuroleptic drugs: mirtazapine 30 mg daily (p.d.) and halperidol 10 mg p.d.. When both the depressive and psychotic symptoms were treatment-resistant, even after a change from mirtazapine to venlafaxine (300 mg p.d.), the drug regimen was changed to sertraline, 150 mg p.d., and olanzapine, 20 mg p.d.. While this brought about improvement, his condition deteriorated when olanzapine was withdrawn. But all symptoms completely disappeared when olanzapine was again given. Spontaneous remission in the future thus seems unlikely to occur.. This case illustrates that the atypical antipsychotic drug olanzapine has some advantages over such typical antipsychotic drug olanzapine has some advantages over such typical antipsychotic medication as butyrophenone. The underlying mechanism for this greater efficacy is probably the difference in receptor-binding capacity between these drugs, the former inhibiting some serotonin receptors so that it is synergistic with antidepressives that inhibit serotonin transport.

Topics: Antidepressive Agents, Second-Generation; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Drug Therapy, Combination; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Sertraline; Treatment Outcome

Mood-stabilizing agents are ideally conceptualized as possessing antimanic and antidepressant properties. While research on olanzapine's antimanic effects is growing, data on its possible antidepressant properties are limited. We sought to determine if olanzapine is effective in the add-on treatment of major affective disorders, particularly depressive symptoms, in a naturalistic setting.. All charts of patients meeting DSM-IV criteria for bipolar disorder or unipolar major depressive disorder treated with olanzapine in a private psychiatric practice were reviewed and clinical response was assessed retrospectively using the Clinical Global Impression Scale for Improvement (CGI-I).. Olanzapine was moderately effective in 6/10 (60%) patients. Side-effects were present in 8/10 (80%), most commonly weight gain.. Olanzapine appears to be moderately effective in open add-on treatment in patients with mainly depressive symptoms. Accumulating evidence suggests that olanzapine, and atypical antipsychotics in general, possess mild to moderate adjunctive antidepressant properties.

Topics: Adult; Aged; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder, Major; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Retrospective Studies; Treatment Outcome

Topics: Anti-Infective Agents; Antipsychotic Agents; Benzodiazepines; Ciprofloxacin; Cytochrome P-450 CYP1A2; Cytochrome P-450 CYP1A2 Inhibitors; Depressive Disorder, Major; Drug Interactions; Drug Therapy, Combination; Enzyme Inhibitors; Enzyme Repression; Female; Humans; Middle Aged; Olanzapine; Pirenzepine

Olanzapine has emerged as an atypical antipsychotic with few side effects and potentially superior efficacy in the treatment of schizophrenia. To our knowledge there have been few published reports of olanzapine in the treatment of mood disorders. We report on the adjunctive use of this medication in three subjects with mania and two with depression. Response occurred rapidly and patients tolerated the medication. Olanzapine offers promise in the treatment of mood disorders.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Delusions; Depressive Disorder, Major; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Middle Aged; Olanzapine; Pirenzepine; Recurrence