Clinical Trials Support New Algorithm for Treating Pediatric Bipolar Mania: 4 Atypical Antipsychotics Are Proposed as First-Line Therapy, Based on Current Evidence

Five recent randomized controlled trials (RCTs) have demonstrated the efficacy of atypical antipsychotics for treating bipolar disorder in children and adolescents, but 4 of these 5 trials remain unpublished. The lag time between the completion of these trials and publication of their results--typically 4 to 5 years (1)--leaves psychiatrists without important evidence to explain to families and critics (2) why they might recommend using these powerful medications in children with mental illness. [ILLUSTRATION OMITTED] This article previews the preliminary results of these 5 RCTs of atypical antipsychotics, offers a treatment algorithm supported by this evidence, and discusses how to manage potentially serious risks when using antipsychotics to treat children and adolescents with bipolar disorder (BPD). Where do atypical antipsychotics fit in? Details of the 5 industry-sponsored RCTs of atypical antipsychotics in children and adolescents with bipolar I manic or mixed episodes are summarized in Table 1 (page 24). (3-7) Only the olanzapine study (4) has been published; data from the other 4 trials were presented at medical meetings in 2007 and 2008. Table 1 RCTs of atypical antipsychotics in patients age 10 to 17 with bipolar I disorder * Antipsychotic and source Bipolar I Trial Dosage (mg/d) episode (# of duration subjects) (days) Risperidone Manic, mixed 21 0.5 to 2.5 Pandina et al (3) (169) 3 to 6 AACAP 2007 Olanzapine Manic, mixed 21 10.4 [+ or -] 4.5 Tohen et al (4) (161) Quetiapine Manic 21 400 DelBello et al (5) (284) 600 AACAP 2007 Aripiprazole Manic, mixed 28 10 Wagner et al (6) (296) 30 ACNP 2007 Ziprasidone Manic, mixed 28 80 to 160 DelBello et al (7) (238) APA 2008 Antipsychotic and source Response rate or NNT Mean weight YMRS score change gain (kg) Risperidone 59% 3.3 1.9 Pandina et al (3) 63% 3.5 1.4 AACAP 2007 Olanzapine 49% 4.1 3.7 Tohen et al (4) [+ or -] 2.2 Quetiapine 64% 4.4 1.7 DelBello et al (5) 58% 4.2 1.7 AACAP 2007 Aripiprazole 45% 4.1 0.9 Wagner et al (6) 64% 2.4 0.54 ACNP 2007 Ziprasidone -13.83 with 3.7 None DelBello et al (7) ziprasidone, APA 2008 -8.61 with placebo * Each trial included a 6-month open extension phase; results are pending AACAP: American Academy of Child and Adolescent Psychiatry; ACNP: American College of Neuropsychopharmacology; APA: American Psychiatric Association; NNT: number needed to treat; RCT: randomized controlled trial; YMRS: Young Mania Rating Scale Change in Young Mania Rating Scale (YMRS) score was the primary outcome measure in these 5 trials, and each compound was more effective than placebo. The trials demonstrated statistically significant and clinically relevant differences between each antipsychotic and a placebo. The number needed to treat (NNT)--how many patients need to be treated for 1 to benefit in a controlled clinical trial--ranged from 2 to 4. For comparison, the NNT for statins in the prevention of coronary events is 12 to 22, (8) and the NNT in an analysis of trials of selective serotonin reuptake inhibitors for pediatric major depressive disorder was 9. (9) Thus, an NNT of [less than or equal to] 4 represents a clinically significant effect. …