Gustavo H Vázquez1, Jessica N Holtzman2, Leonardo Tondo3, Ross J Baldessarini4. 1. International Consortium for Bipolar and Psychotic Disorder Research, McLean Hospital, Belmont, MA, United States; Department of Neuroscience, Palermo University, Buenos Aires, Argentina. Electronic address: gvazquez@palermo.edu. 2. Department of Neuroscience, Palermo University, Buenos Aires, Argentina; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, United States. 3. International Consortium for Bipolar and Psychotic Disorder Research, McLean Hospital, Belmont, MA, United States; Department of Psychiatry, Harvard Medical School, Boston, MA, United States; Lucio Bini Mood Disorder Centers, Cagliari & Rome, Italy; Lucio Bini Mood Disorder Center, Rome, Italy. 4. International Consortium for Bipolar and Psychotic Disorder Research, McLean Hospital, Belmont, MA, United States; Department of Psychiatry, Harvard Medical School, Boston, MA, United States.
Abstract
BACKGROUND: Depression in bipolar disorder is a major therapeutic challenge associated with disability and excess mortality. METHODS: We reviewed findings from randomized placebo-controlled trials concerning efficacy and adverse effects of treatments for acute bipolar depression, including anticonvulsants, antidepressants, lithium, and modern antipsychotics, to compare numbers-needed-to-treat (NNT) versus -to-harm (NNH). RESULTS: Included were data from 22 reports involving 33 drug-placebo pairs. Antidepressants (especially modern drugs) had the most favorable (highest) risk/benefit ratio (pooled NNH/NNT=18.1). Anticonvulsants were effective agents (pooled NNT=5.06), but carbamazepine and valproate were not as well tolerated (NNH<10) as lamotrigine, and they had an unfavorable pooled NNH/NNT (3.75). Some antipsychotics (lurasidone, olanzapine+fluoxetine, and quetiapine (NNT all < 10) were effective though aripiprazole and ziprasidone were not (NNT≥45); olanzapine alone was weakly effective (NNT=11.3), and all but lurasidone (NNH=20.2) were not well tolerated (NNH≤4.18). Lithium appeared to be poorly effective but well tolerated in only one trial. CONCLUSIONS: Some anticonvulsants and antipsychotics seemed effective for acute bipolar depression, but most antipsychotics were not well tolerated. Antidepressants were effective and well-tolerated; lithium remains inadequately tested. LIMITATIONS: There are remarkably few short-term treatment trials (2.75/12 treatments), and fewer long-term trials for bipolar depression, possibly arising from exaggerated concerns about inducing mania.
BACKGROUND:Depression in bipolar disorder is a major therapeutic challenge associated with disability and excess mortality. METHODS: We reviewed findings from randomized placebo-controlled trials concerning efficacy and adverse effects of treatments for acute bipolar depression, including anticonvulsants, antidepressants, lithium, and modern antipsychotics, to compare numbers-needed-to-treat (NNT) versus -to-harm (NNH). RESULTS: Included were data from 22 reports involving 33 drug-placebo pairs. Antidepressants (especially modern drugs) had the most favorable (highest) risk/benefit ratio (pooled NNH/NNT=18.1). Anticonvulsants were effective agents (pooled NNT=5.06), but carbamazepine and valproate were not as well tolerated (NNH<10) as lamotrigine, and they had an unfavorable pooled NNH/NNT (3.75). Some antipsychotics (lurasidone, olanzapine+fluoxetine, and quetiapine (NNT all < 10) were effective though aripiprazole and ziprasidone were not (NNT≥45); olanzapine alone was weakly effective (NNT=11.3), and all but lurasidone (NNH=20.2) were not well tolerated (NNH≤4.18). Lithium appeared to be poorly effective but well tolerated in only one trial. CONCLUSIONS: Some anticonvulsants and antipsychotics seemed effective for acute bipolar depression, but most antipsychotics were not well tolerated. Antidepressants were effective and well-tolerated; lithium remains inadequately tested. LIMITATIONS: There are remarkably few short-term treatment trials (2.75/12 treatments), and fewer long-term trials for bipolar depression, possibly arising from exaggerated concerns about inducing mania.
Authors: Konstantinos N Fountoulakis; Lakshmi Yatham; Heinz Grunze; Eduard Vieta; Allan Young; Pierre Blier; Siegfried Kasper; Hans Jurgen Moeller Journal: Int J Neuropsychopharmacol Date: 2017-02-01 Impact factor: 5.176
Authors: Jonathan B Savitz; T Kent Teague; Masaya Misaki; Matt Macaluso; Brent E Wurfel; Matt Meyer; Douglas Drevets; William Yates; Ondria Gleason; Wayne C Drevets; Sheldon H Preskorn Journal: Transl Psychiatry Date: 2018-01-24 Impact factor: 6.222