PSYCHIATRICNEWS alert[The Voice of the American Psychiatric Association and the Psychiatric Community]December 30, 2014A combination of the antipsychotic olanzapine and the antidepressant fluoxetine proved superior to placebo for acute treatment of bipolar I depression in patients aged 10-17 in a randomized control trial published online in the Journal of the American Academy of Child and Adolescent Psychiatry.
The double-blind study by researchers at Eli Lilly and Company randomized 170 young patients with bipolar I disorder experiencing an acute depressed episode to the olanzapine/fluoxetine combination [OFC] and 85 to placebo for up to eight weeks of treatment. The primary efficacy measure was mean change in the Children’s Depression Rating Scale-Revised [CDRS-R]…
Olanzapine/Fluoxetine Combination in Children and Adolescents With Bipolar I Depression: A Randomized, Double-Blind, Placebo-Controlled Trialby Holland C. Detke, Ph.D., Melissa P. DelBello, M.D., John Landry, M.Math, and Roland W. Usher, M.S.Journal of the American Academy of Child and Adolescent Psychiatry. published online 12/24/2014
Objective: To assess the efficacy and safety of olanzapine/fluoxetine combination [OFC] for the acute treatment of bipolar depression in children and adolescents.Method: Patients 10-17 years of age with bipolar I disorder [BP-I], depressed episode, baseline Children’s Depression Rating Scale-Revised [CDRS-R] total score ≥40, Young Mania Rating Scale [YMRS] total score ≤15, and YMRS-item 1 ≤2 were randomized to OFC [6/25-12/50 mg/day olanzapine/fluoxetine; n=170] or placebo [n=85] for up to 8 weeks of double-blind treatment. The primary efficacy measure was mean change in CDRS-R using mixed-model repeated measures methodology.Results: Baseline-to-week-8 least-squares mean change in CDRS-R total score was greater for OFC-treated patients than for placebo-treated patients [-28.4 vs. -23.4, p=.003; effect size=.46], with between-group differences statistically significant at week 1 [p=.02] and all subsequent visits [all p<.01]. Rates of and times to response and remission were statistically significantly greater for OFC- than placebo-treated patients. The most frequent treatment-emergent adverse events in the OFC group were weight gain, increased appetite, and somnolence. Mean weight gain at patient’s endpoint was significantly greater for OFC- than placebo-treated patients [4.4 kg vs. 0.5 kg, p<.001]. Treatment-emergent hyperlipidemia was very common among OFC-treated patients. Abnormal increases in hepatic analytes, prolactin, and corrected QT interval [QTc] were also common or very common but generally not clinically significant.Conclusion: OFC was superior to placebo and approved by the US Food and Drug Administration [FDA] for the acute treatment of bipolar I depression in patients 10-17 years of age. Benefits should be weighed versus the risk of adverse events, particularly weight gain and hyperlipidemia.
It’s not my intention to specifically challenge these results. But since the DSM-III, there has been a steady creep in diagnosing Bipolar Disorder from the classic Manic-Depressive Illness of Kraepelin’s days. And I see a remarkable number of people who announce that they’ve been "told they are Bipolar" and they simply don’t fit. Also, in reviewing the more papers on Pediatric Bipolar Disorder, my skepticism level hovers around DEFCON 1. Likewise, I see no reason for a COMBO medication. Taking two pills a day if they’re needed is no great burden. So my suspicions that the goals here are commercial rather than medical. But I don’t doubt that depressed adolescents feel better taking Zyprexa® or Symbiax®. I question whether it’s a good idea to prescribe it, particularly in the fixed dose COMBO pills. But the fact that it is a likely ghost-written, industry produced, COI-laden, commercially-driven RCT is not all that bothers me about this study.
This study does seem dubious. But I want to differ with you about the credibility of Bipolar Disorder in childhood/adolesence. I think that most researchers and clinicians in the area of Bipolar Disorder (who accept the concept of Bipolar/Manic-Depressive Ilness) will agree that a substantial percentage of people diagnosed as Bipolar have their initial episodes in adolescence, and a smaller percentage in pre-adolescence. For example, see this retrospective study: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3266753/
Biederman and others are controversial not because they claimed Bipolar Disorder can begin before adulthood, but because they advocated that it has a different symptomatology at those ages, thus expanding the population eligible for such a diagnosis.