Mental health

Antidepressant medicines in individuals with a depressive episode in bipolar disorder

Question 9: In individuals presenting with a depressive episode in bipolar disorder, are antidepressant medicines effective and safe?

Management of psychosis and bipolar disorders

  • Population: adults with bipolar depression
  • Interventions: antidepressants or adjunctive antidepressants
  • Comparison: placebo, or mood stabilizer and placebo
  • Outcomes:
    • symptoms severity
    • disability and functioning
    • adverse effects of treatment
    • quality of life
    • mortality
    • treatment adherence
    • users' and families' satisfaction with care.


Antidepressant medicines, always in combination with a mood stabilizer (lithium or valproate), may be considered in the treatment of moderate or severe depressive episodes of bipolar disorder. Selective serotonin reuptake inhibitors (SSRI; fluoxetine) should be preferred to tricyclic antidepressants (TCA).
Strength of recommendation: STANDARD

Antidepressant treatment should begin at a low dose and be increased gradually if necessary.
Individuals should be monitored carefully for early symptoms or signs of manic symptoms. Antidepressant medication should be stopped soon after remission of depressive symptoms, while mood stabilizer should be continued.
Strength of recommendation: STRONG

Evidence profile