clozapine and Disruptive--Impulse-Control--and-Conduct-Disorders

The risk of suicide for schizophrenia patients is 20 to 50 times higher than that for the general population. Long-term treatment with clozapine, an atypical antipsychotic, has been shown to reduce the rate of suicide by 80% to 85%. The goal of the present study was to examine whether clozapine's effect on the reduction of suicidal behavior in chronic schizophrenic patients could be due to a reduction in impulsive-aggressive behavior.. 44 patients with chronic DSM-IV schizophrenia were treated with clozapine or haloperidol decanoate in an open prospective 6-month trial. Changes in measures of suicidality, impulsiveness, aggression, depressed mood, and positive and negative symptoms were assessed at baseline and at 6 months.. The clozapine-treated group (N = 18) had a significantly greater reduction on all outcome measures compared with the haloperidol decanoate-treated group (N = 26). Only in the clozapine-treated group did the reduction in measures of suicidality correlate significantly with a reduction in impulsiveness and aggression. The reductions in suicidality and impulsive aggression were not significantly correlated with reductions in depressed mood or positive and negative symptom scores in either group.. These data suggest that the reduction in suicidality following long-term clozapine treatment may be related to a reduction in impulsiveness and aggression.

Topics: Adolescent; Adult; Aggression; Antipsychotic Agents; Chronic Disease; Clozapine; Diagnostic and Statistical Manual of Mental Disorders; Disruptive, Impulse Control, and Conduct Disorders; Drug Administration Schedule; Female; Haloperidol; Humans; Male; Middle Aged; Schizophrenia; Suicide, Attempted

To compare the efficacy of clozapine with typical antipsychotic drugs in controlling impulsivity and to explore the possible correlation of impulsivity with plasma 5-hydroxytryptamine (5-HT) levels, plasma 5-hydroxyindoleacetic acid (5-HIAA) levels and plasma 5-HT turnover.. Prospective, cross-sectional study open to medication and blinded to biochemical analyses.. Healthy control subjects (n = 24) and 46 inpatients and outpatients meeting the DSM-IV criteria for schizophrenia; 20 were being treated with clozapine and 26 were taking typical antipsychotic drugs.. All psychotropic drugs other than clozapine or typical antipsychotic drugs were discontinued for at least 5 days and subjects fasted overnight before they were assessed.. Coccaro Impulsivity Scale scores, plasma 5-HT levels, 5-HIAA levels and 5-HT turnover.. Patients treated with clozapine and those treated with typical antipsychotics had significantly higher impulsivity scores than the control group, and the mean impulsivity score of the typical antipsychotic group was significantly higher than that of patients treated with clozapine. The mean concentration of 5-HT of the typical antipsychotic group was significantly lower than that of the control group and patients treated with clozapine; however, mean plasma levels of 5-HIAA were significantly higher for the clozapine group than the other 2 groups. 5-HT turnover was significantly higher for the 2 drug-treatment groups than for the control group.. These results suggest that treatment with clozapine should be considered for patients with schizophrenia who are impulsive and aggressive.

Topics: Adult; Antipsychotic Agents; Clozapine; Cross-Sectional Studies; Disruptive, Impulse Control, and Conduct Disorders; Female; Humans; Male; Prospective Studies; Schizophrenia; Serotonin; Serotonin Antagonists

There are limited data in the literature regarding clozapine use in adolescents with diagnoses other than schizophrenia. This report describes the use of clozapine in adolescents with diagnoses of bipolar disorder, intermittent explosive disorder (IED), and posttraumatic stress disorder (PTSD).. A chart review of 39 adolescents treated with clozapine at two residential facilities was undertaken. Data extraction included demography, illness variables, medication information, and clinical outcomes. Categorical outcomes were analyzed using contingency statistics, and continuous variables were analyzed using a paired t test.. The cohort included 26 females and 13 males with a mean age of 14 years. Clozapine was titrated slowly, and the mean daily dose was 102 mg. The diagnoses included bipolar disorder (n = 7), IED (n = 9), and PTSD (n = 19). There were significant reductions in polypharmacy once the clozapine dosage was stabilized. Prior to clozapine treatment, nearly 70% of the subjects were receiving either mood-stabilizing or antidepressant agents in combination with the previous antipsychotic drug. Once the clozapine dosage was stabilized, only 24% of the subjects required concomitant mood stabilizers (p < 0.001), and only 21% of the subjects required concomitant antidepressants (p < 0.001). Anxiolytic medication use was also significantly reduced during clozapine treatment. Most patients were discharged to a less restrictive setting. Eight subjects discontinued clozapine due to agranulocytosis (n = 1), neutropenia (n = 2), excessive weight gain (n = 2), or not requiring it long term (n = 1), and data were unavailable in 2 subjects. Significant weight gain (5% or greater change from baseline) was noted in 20 subjects.. Clozapine, in relatively modest doses, appears to have clinical benefits for adolescent with bipolar disorder, IED, and PTSD. There is no labeled indication for clozapine use in these disorders. Clozapine is also associated with serious side effects in subsets of individuals. Therefore, a very careful evaluation of the risk-to-benefit ratio in each individual subject being considered for clozapine is highly recommended.

Topics: Adolescent; Bipolar Disorder; Chi-Square Distribution; Child; Clozapine; Disruptive, Impulse Control, and Conduct Disorders; Female; Humans; Male; Retrospective Studies; Stress Disorders, Post-Traumatic; Weight Gain