Is there a 'weight neutral' second-generation antipsychotic for bipolar disorder?

Antipsychotic-induced weight gain (WG) and metabolic abnormalities are major concerns. This review was untaken to answer if there is a weight-neutral second-generation antipsychotic for bipolar disorder (BPD). Areas covered: English-language literature in MEDLINE was searched with the keywords of antipsychotic/second-generation antipsychotic or generic/brand name of second-generation antipsychotic, and BPD/mania/depression or bipolar maintenance, and safety/tolerability or WG/weight increase, and randomized, placebo-controlled trial. Difference between an antipsychotic monotherapy and placebo in absolute weight gain (AWG) and/or ≥ 7% (WG in three phases of BPD was compared based on the data from original publications. The number needed to treat to harm was used for the comparison of ≥ 7% WG. Among antipsychotics with short-term (mania and/or bipolar depression) and long-term (maintenance) studies, olanzapine, asenapine, quetiapine, risperidone had significant WG compared to placebo in both short-term and long-term trials. Aripiprazole did not cause significant WG compared to placebo in short-term studies, but caused significant WG in long-term studies. Paliperidone-ER-induced WG was significant in a mania study as measured with AWG, and ziprasidone caused significant WG in a mania study measured with ≥ 7% WG. Expert commentary: These data suggest that it is unlikely there is a weight-neutral second-generation antipsychotic in BPD.