title: Efficacy and tolerability of treatments for bipolar depression.
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.
  
  
  CONCLUSIONS
  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.affiliation: 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.
authors.forename: Gustavo H
authors.initials: GH
authors.lastname: Vázquez
authors.affiliation: Department of Neuroscience, Palermo University, Buenos Aires, Argentina; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, United States.
authors.forename: Jessica N
authors.initials: JN
authors.lastname: Holtzman
authors.affiliation: 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.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Tondo
authors.affiliation: International Consortium for Bipolar and Psychotic Disorder Research, McLean Hospital, Belmont, MA, United States; Department of Psychiatry, Harvard Medical School, Boston, MA, United States.
authors.forename: Ross J
authors.initials: RJ
authors.lastname: Baldessarini
mesh_terms: D000927:Anticonvulsants / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000009:adverse effects / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005473:Fluoxetine / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D000069056:Lurasidone Hydrochloride / Q000009:adverse effects / Q000627:therapeutic use*; D000069348:Quetiapine Fumarate / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic
chemical_list: D000927:Anticonvulsants; D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D004338:Drug Combinations; C492572:olanzapine-fluoxetine combination; D005473:Fluoxetine; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; D000069056:Lurasidone Hydrochloride
keywords: Bipolar depression; Number-needed-to-harm (NNH); Number-needed-to-treat (NNT); Treatments