title: The off-label use of clozapine in adolescents with bipolar disorder, intermittent explosive disorder, or posttraumatic stress disorder.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Head Injury Clinic, Pittsburgh, Pennsylvania, USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Kant
authors.forename: Ranjit
authors.initials: R
authors.lastname: Chalansani
authors.forename: K N Roy
authors.initials: KN
authors.lastname: Chengappa
authors.forename: Mary F
authors.initials: MF
authors.lastname: Dieringer
mesh_terms: D000293:Adolescent; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000523:psychology; D016009:Chi-Square Distribution; D002648:Child; D003024:Clozapine / Q000009:adverse effects / Q000627:therapeutic use*; D007174:Disruptive, Impulse Control, and Conduct Disorders / Q000188:drug therapy* / Q000523:psychology; D005260:Female; D006801:Humans; D008297:Male; D012189:Retrospective Studies; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy* / Q000523:psychology; D015430:Weight Gain / Q000187:drug effects / Q000502:physiology
chemical_list: D003024:Clozapine