title: Comparative efficacy and acceptability of drug treatments for bipolar depression: a multiple-treatments meta-analysis.
abstract: OBJECTIVE
  Treatment of bipolar depression is complicated by variable response and risk of switch to mania. Guidance is informed by the strength of evidence rather than by comparative data.
  
  
  METHODS
  We performed a multiple-treatments meta-analysis of randomised, double-blind, controlled comparisons of 4-16 weeks in adults in bipolar depression. The primary efficacy outcome was effect size. The primary acceptability outcome was 'switch to mania'. Secondary outcomes were likelihood of response and withdrawals from trials.
  
  
  RESULTS
  Twenty-nine studies were included (8331 participants). Olanzapine + fluoxetine and olanzapine performed best on primary outcome measure being ranked highest for effect size. Switch to mania was least likely with ziprasidone and then quetiapine. Olanzapine + fluoxetine was also ranked the highest for response with lurasidone second, but olanzapine + fluoxetine and olanzapine had the optimal effect on response and withdrawal from treatment when the two parameters were considered together. Several treatments [monoamine oxidase inhibitors (MAOIs), ziprasidone, aripiprazole and risperidone] have limited or no therapeutic activity in bipolar depression.
  
  
  CONCLUSIONS
  Olanzapine + fluoxetine should be first-line treatment. Olanzapine, quetiapine, lurasidone, valproate and selective serotonin re-uptake inhibitors are also recommended. Tricyclic antidepressants and lithium are worthy of consideration but lamotrigine (high risk of switching, less robust efficacy) and MAOIs, ziprasidone, aripiprazole and risperidone (no evidence of efficacy) should not be used.
authors.affiliation: Pharmacy Department, Maudsley Hospital, Denmark Hill, London, UK; Institute of Pharmaceutical Science, King's College London, London, UK.
authors.forename: D M
authors.initials: DM
authors.lastname: Taylor
authors.forename: V
authors.initials: V
authors.lastname: Cornelius
authors.forename: L
authors.initials: L
authors.lastname: Smith
authors.forename: A H
authors.initials: AH
authors.lastname: Young
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D000068180:Aripiprazole; D001569:Benzodiazepines / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000523:psychology; D003863:Depression / Q000188:drug therapy* / Q000523:psychology; D003987:Dibenzothiazepines / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005473:Fluoxetine / Q000627:therapeutic use; D006801:Humans; D054833:Isoindoles / Q000627:therapeutic use; D000077213:Lamotrigine; D018020:Lithium Compounds / Q000627:therapeutic use; D000069056:Lurasidone Hydrochloride; D008996:Monoamine Oxidase Inhibitors / Q000627:therapeutic use; D000077152:Olanzapine; D010879:Piperazines / Q000627:therapeutic use; D000069348:Quetiapine Fumarate; D015363:Quinolones / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D018967:Risperidone / Q000627:therapeutic use; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D013844:Thiazoles / Q000627:therapeutic use; D016896:Treatment Outcome; D014227:Triazines / Q000627:therapeutic use; D014635:Valproic Acid / Q000627:therapeutic use
chemical_list: D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D000068180:Aripiprazole; D001569:Benzodiazepines; D003987:Dibenzothiazepines; D005473:Fluoxetine; D054833:Isoindoles; D000077213:Lamotrigine; D018020:Lithium Compounds; D000069056:Lurasidone Hydrochloride; D008996:Monoamine Oxidase Inhibitors; D000077152:Olanzapine; D010879:Piperazines; D000069348:Quetiapine Fumarate; D015363:Quinolones; D018967:Risperidone; D017367:Selective Serotonin Reuptake Inhibitors; D013844:Thiazoles; D014227:Triazines; D014635:Valproic Acid; C092292:ziprasidone
keywords: antidepressives; antipsychotics; bipolar disorder; depression