Controlled, dose-response study of sertindole and haloperidol in the treatment of schizophrenia

Objective: This multicenter, double-blind, placebo-controlled study evaluated the efficacy and safety of three doses of sertindole (12, 20, and 24 mg/day) and haloperidol (4, 8, and 16 mg/day) in the treatment of psychotic symptoms for 497 hospitalized patients with schizophrenia. Method: The patients were randomly assigned to one of the medication groups and received treatment for 8 weeks. Changes in Positive and Negative Syndrome Scale, Scale for the Assessment of Negative Symptoms, Brief Psychiatric Rating Scale, and Clinical Global Impression scores were used as evaluations of treatment efficacy. Three rating scales were used to assess extrapyramidal symptoms as well as the occurrence of adverse events and the use of medications related to extrapyramidal symptoms. Results: Both sertindole and haloperidol were comparably effective in the treatment of psychosis, and all dose levels were significantly more effective than placebo. For the treatment of negative symptoms, only sertindole, 20 mg/day, was significantly more effective than placebo. For all extrapyramidal symptom measures, sertindole was clinically and statistically indistinguishable from placebo, and rates of extrapyramidal symptoms were not dose related. All dose levels of haloperidol produced significantly more extrapyramidal symptoms than placebo or sertindole. Adverse events associated with sertindole treatment were mild in severity. Conclusions: Sertindole is a new antipsychotic agent effective for the treatment of both the Positive and negative symptoms of schizophrenia, with motor side effects that are indistinguishable from those associated with placebo

Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT)

Background: Approximately 50% of patients with schizophrenia or schizoaffective disorder attempt suicide, and approximately 10% die of suicide. Study results suggest that clozapine therapy significantly reduces suicidal behavior in these patients. Methods: A multicenter, randomized, international, 2-year study comparing the risk for suicidal behavior in patients treated with clozapine vs olanzapine was conducted in 980 patients with schizophrenia or schizoaffective disorder, 26.8% of whom were refractory to previous treatment, who were considered at high risk for suicide because of previous suicide attempts or current suicidal ideation. To equalize clinical contact across treatments, all patients were seen weekly for 6 months and then biweekly for 18 months. Subsequent to randomization, unmasked clinicians at each site could make any interventions necessary to prevent the occurrence of suicide attempts. Suicidal behavior was assessed at each visit. Primary end points included suicide attempts (including those that led to death), hospitalizations to prevent suicide, and a rating of "much worsening of suicidality" from baseline. Masked raters, including an independent suicide monitoring board, determined when end point criteria were achieved. Results: Suicidal behavior was significantly less in patients treated with clozapine vs olanzapine (hazard ratio, 0.76; 95% confidence interval, 0.58-0.97; P = .03). Fewer clozapine-treated patients attempted suicide (34 vs 55; P = .03), required hospitalizations (82 vs 107; P = .05) or rescue interventions (118 vs 155; P = .01) to prevent suicide, or required concomitant treatment with antidepressants (221 vs 258; P = .01) or anxiolytics or soporifics (301 vs 331; P = .03). Overall, few of these high-risk patients died of suicide during the study (5 clozapine vs 3 olanzapine-treated patients; P = .73). Conclusions: Clozapine therapy demonstrated superiority to olanzapine therapy in preventing suicide attempts in patients with schizophrenia and schizoaffective disorder at high risk for suicide. Use of clozapine in this population should lead to a significant reduction in suicidal behavior