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      Important clinical features of atypical antipsychotics in acute bipolar depression that inform routine clinical care: a review of pivotal studies with number needed to treat

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          Abstract

          English-language literature cited in MEDLINE from January, 1980 to October 30, 2014 was searched by using terms of antipsychotic, generic and brand names of atypical antipsychotics, “bipolar depression/bipolar disorder”, “placebo”, and “trial”. The parameters of response (≥50% improvement on MADRS, Montgomery-Asberg Depression Rating Scale total score), remission (either ≤12 or 8 on MADRS total score at endpoint), discontinuation due to adverse events (DAEs), somnolence, ≥7% weight gain, overall extrapyramidal side-effects (EPSs), and akathisia, were extracted from originally published primary outcome papers. The number needed to treat to benefit (NNT) for response and remission or harm (NNH) for DAEs or other side effects relative to placebo were estimated and presented with the estimate and 95% confidence interval. Olanzapine monotherapy, olanzapine-fluoxetine combination (OFC), quetiapine-IR monotherapy, quetiapine-XR monotherapy, lurasidone monotherapy, and lurasidone adjunctive therapy were superior to placebo with NNTs for responses of 11–12, 4, 7–8, 4, 4–5, and 7, and NNTs for remission of 11–12, 4, 5–11, 7, 6–7, and 6, respectively. There was no significant difference between OFC and lamotrigine, and between aripiprazole or ziprasidone and placebo in response and remission. Olanzapine monotherapy, quetiapine-IR, quetiapine-XR, aripiprazole, and ziprasidone 120–160 mg/day had significantly increased risk for DAEs with NNHs of 24, 8–14, 9, 12, and 10, respectively. For somnolence, quetiapine-XR had the smallest NNH of 4. For ≥7% weight gain, olanzapine monotherapy and OFC had the smallest NNHs with both of 5. For akathisia, aripiprazole had the smallest NNH of 5. These findings suggest that among the FDA-approved agents including OFC, quetiapine-IR and -XR, lurasidone monotherapy and adjunctive therapy to a mood stabilizer, the differences in the NNTs for response and remission are small, but the differences in NNHs for DAEs and common side-effects are large. Therefore, the selection of an FDA-approved atypical antipsychotic for bipolar depression should be based upon safety and tolerability.

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          Author and article information

          Contributors
          Keming.gao@uhhospitals.org
          Journal
          Neurosci Bull
          Neurosci Bull
          Neuroscience Bulletin
          Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (Shanghai )
          1673-7067
          1995-8218
          30 May 2015
          October 2015
          : 31
          : 5
          : 572-588
          Affiliations
          [1 ] GRID grid.443867.a, ISNI 0000000091494843, Department of Psychiatry, Case Western Reserve University School of Medicine and Mood Disorders Program, , University Hospitals Case Medical Center, ; Cleveland, Ohio USA
          [2 ] GRID grid.16821.3c, ISNI 0000000403688293, Division of Mood Disorders, Shanghai Mental Health Center, , Shanghai Jiao Tong University School of Medicine, ; Shanghai, 200030 China
          [3 ] GRID grid.452708.c, ISNI 0000000418030208, , Institute of Mental Health of Second Xiangya Hospital of Central South University, ; Changsha, 410011 China
          [4 ]Mood Disorders Program of Hongkou District Mental Health Center of Shanghai, Shanghai, 200083 China
          Article
          PMC5563672 PMC5563672 5563672 1534
          10.1007/s12264-014-1534-0
          5563672
          26024955
          d0be794e-6d70-4841-8227-f9d5c6562d38
          © Shanghai Institutes for Biological Sciences, CAS and Springer-Verlag Berlin Heidelberg 2015
          History
          : 4 June 2014
          : 4 March 2015
          Categories
          Review
          Custom metadata
          © Shanghai Institutes for Biological Sciences, CAS and Springer-Verlag Berlin Heidelberg 2015

          atypical antipsychotic,number needed to treat,efficacy,bipolar depression,tolerability,weight gain,somnolence,extrapyramidal side-effects,akathisia

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