A new study on the safety and efficacy of Symbyax (olanzapine/ fluoxetine combination or OFC) in kids with bipolar I depression is in press and will be published soon.
Since Symbyax is now available asa generic, it may be surprising to seethat this study is funded by the brand name manufacturer (Eli Lilly), however, the study was required by the USFood and Drug Administration (FDA) under the Pediatric Research Equity Act (PREA). PREA allows the FDA to require pediatric studies for certain drugs when the agency believes they may be useful for this age group. Regardless of the motivation, this is a welcome study, since pediatric bipolar depression remains an understudied area.
The study included 255 kids between 10 and 17 years old with a moderately severe depressive episode of bipolar illness. Two-thirds of the participants received OFC (flexible dosing of 6 mg/25 mg, 6 mg/50 mg, 12 mg/25 mg, or 12 mg
/50 mg/day olanzapine/fluoxetine with the most common dose being 12 mg/50 mg/day) and one-third received placebo for eight weeks in a double-blind, controlled fashion. The primary efficacy measure was the Children’s Depression Rating Scale-Revised (CDRS-R).
Kids on OFC did significantly better on the CDRS-R than those on placebo as early as the first week and maintained this difference throughout the eight weeks. And, although placebo response was high, response and remission were significantly higher in the OFC group than the placebo group (78% vs. 59% responded and 59% vs. 43% remitted).
In terms of side effects, there were no big surprises: OFC caused significantly more weight gain, increased appetite, sedation, somnolence, and tremor compared with placebo. Kids on OFC gained an average of 11 pounds over eight weeks compared to kids taking placebo who gained an average of one pound. In terms of weight, 52% of OFC kids gained ≥7% of baseline body weight (FDA’s definition of significant weight gain), compared to 4% of placebo kids. Elevated prolactin occurred significantly more in the OFC group and five of the girls taking OFC were symptomatic with menstrual changes and lactation. QT interval was prolonged more significantly in the OFC group as well, and this
was likely due more to the fluoxetine component than the olanzapine.
OFC is currently the only FDA- approved treatment for bipolar depression in kids. For adults, there are more options: Latuda and Seroquel XR are approved and Lamictal has some positive data to support its use. Of these three, you can eliminate Seroquel as a potential treatment for kids because two controlled trials found it no better than placebo. Latuda data in kids will likely be forthcoming (Detke HC et al, J Am Acad Child Adolesc Psychiatry 2015;ahead of print).
CCPR’s Take: OFC is an optionfor bipolar depression in kids, but its high side effect burden will likely causeit to gather dust on pharmacy shelves. However, the fact that a combination antidepressant/atypical antipsychotic has been shown effective for pediatric bipolar depression is good news. It gives us an excuse to try other such combinations off-label, using less weight-inducing antipsychotics, such as Abilify or Latuda.
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