Emerging role of sertindole in the management of schizophrenia.

The atypical antipsychotic sertindole is a phenylindole-derived compound that has affinity for and functions as an antagonist at a number of receptor systems, including dopamine D2 receptors, 5-HT(2A) and 5-HT(2C) receptors, and α-1-noradrenergic receptors. Although previous data suggested that sertindole was well tolerated and had good efficacy against both positive and negative symptom clusters, reports of QT prolongation with sertindole prompted its voluntary removal from the market in 1998. After further safety analyses, it recently regained approval and was reintroduced to the European market for the treatment of schizophrenia, where its role in therapy among available atypicals remains unclear. This article evaluates the preclinical and clinical data regarding sertindole's effectiveness and concludes that sertindole continues to demonstrate a number of strengths, including effective management of both positive and negative symptoms, well-tolerated side effects (including little or no sedation, weight gain, and extrapyramidal side effects), and a superior procognitive profile that is unique among atypical antipsychotics. However, minor concerns regarding its sexual side effects and the major consideration of QT prolongation suggest that additional comparative effectiveness studies are needed to determine the superiority of sertindole vs other atypical antipsychotics recently introduced.

Hospital use of antipsychotic drugs: polytherapy.

OBJECTIVE: Growing acceptance of new psychotropic drugs encouraged a survey of current use of antipsychotic drugs alone and in combinations, with comparisons with previous findings. METHOD: Records from a random sample of McLean Hospital (Belmont, Mass) inpatients treated with an antipsychotic from March to May 2004 were reviewed for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, discharge diagnosis; all current psychotropic drug treatments; initial, peak, and final chlorpromazine-equivalent milligram-per-day dose of antipsychotics (APD); initial, peak, and final lithium-equivalent dose (milligram per day) of mood stabilizers (MS); weight change; clinical status at admission and discharge; and days of hospitalization. RESULTS: In the 305 inpatients sampled (n = 184 women, 60.3%), Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, clinical conditions ranked as follows: major affective (n = 161, 52.8%), psychotic (n = 99, 32.5%), and other disorders (n = 45, 14.8%). Modern drugs comprised 92% of antipsychotic prescriptions, and quetiapine (usually at low doses) was most frequently prescribed. "Polytherapy" (simultaneous treatment with > or =2 psychotropic agents) at discharge was identified in 80% of antipsychotic-treated patients. Use of at least 2 antipsychotics (in 23% of cases) was associated with a 2.8-fold increase in total dose vs monotherapy (651 +/- 403 vs 232 +/- 205 mg/d). Total antipsychotic doses also were higher with mood stabilizer (most often divalproex) or sedative (usually high-potency benzodiazepine) cotreatment, use of older neuroleptics, psychotic-disorder diagnoses, and substance use comorbidity. Polytherapy was not associated with superior clinical improvement or shorter hospitalization but was associated with higher body weight. CONCLUSIONS: Polytherapy involving antipsychotic drugs continues to increase despite limited empirical evidence for greater effectiveness or of safety of such combinations.

An observational study of the effectiveness and safety of intramuscular olanzapine in the treatment of acute agitation in patients with bipolar mania or schizophrenia/schizoaffective disorder.

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

Use of combinations of antipsychotics: McLean Hospital inpatients, 2002.

BACKGROUND: The empirical use of combinations of antipsychotic agents appears to be increasing with little research support for the relative efficacy, safety or cost-effectiveness of this practice. Such treatment was evaluated in hospitalized psychiatric patients. METHODS: Samples of consecutive inpatients treated with > or = 2 ('polytherapy') vs 1 antipsychotic ('monotherapy') were matched on age, sex, diagnosis and admission clinical ratings, and these groups were compared on total daily chlorpromazine-equivalent doses, days in hospital, and changes in clinical ratings between admission and discharge. RESULTS: The study sample included 69 polytherapy and 115 well-matched monotherapy subjects. Despite matching for initial CGI and GAF ratings, polytherapy was associated with high PANSS subscale scores of positive symptoms among affective psychosis, and relatively greater PANSS subscale ratings of excitement-agitation among patients diagnosed with schizophrenia. Estimated clinical improvement during hospitalization was similar among poly- and monotherapy patients, but total daily CPZ-eq doses at discharge averaged twice-greater with polytherapy, and hospitalization lasted 1.5 times longer. CONCLUSIONS: Antipsychotic polytherapy as well as the types of agents combined may reflect clinician responses to particular symptom patterns. The value of specific combinations of antipsychotic agents and their comparison with monotherapies requires specific, prospective, randomized and well-controlled trials that consider matching on clinical characteristics and truly comparable doses across regimens.

Aripiprazole: initial clinical experience with 142 hospitalized psychiatric patients.

BACKGROUND: Aripiprazole is the first dopamine D2 receptor partial-agonist approved for treatment of schizophrenia. Its apparently benign adverse-effect profile encourages broader use in other disorders, especially to limit weight gain associated with other antipsychotic or antimanic agents. We considered the first 6 months of experience with aripiprazole in psychiatric inpatients with a range of disorders. METHODS: We analyzed data obtained from medical records of patients treated with aripiprazole who were hospitalized at McLean Hospital (for 19 +/- 18 days) between December 2002 and June 2003 to evaluate dosing, tolerability, and clinical effects of this new agent in patients diagnosed with DSM-IV psychotic, major affective, or other disorders. RESULTS: Out of a sample of 2766 adult inpatients (65.5% women), 142 were given aripiprazole (mean final daily dose, 16.1 +/- 6.2 mg, 0.20 +/- 0.09 mg/kg body weight) for major affective disorders (52%), primary psychotic disorders (40%), and dementia (8%). CGI ratings improved by 20% on average. Adverse effects were infrequent (15.5%), were three times more likely among women, and most often involved moderate behavioral activation or nausea, with no new episodes of mania. Of the patients who were given aripiprazole, 83% continued it at discharge. Many patients were obese when they were admitted, and obesity was associated with relatively low mg/kg doses of aripiprazole. CONCLUSIONS: Aripiprazole was used in a range of disorders and was generally well tolerated. Adverse effects may reflect its unique dopamine partial-agonist activity. Since aripiprazole is likely to be considered for obese patients, body weight should be considered in establishing adequate doses. Controlled trials of this antipsychotic agent in disorders other than schizophrenia are needed.