Are Antidepressants Associated With New-Onset Suicidality in Bipolar Disorder? A Prospective Study of Participants in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD)

Objective: Depressive episodes are common in bipolar disorder, and the disorder is characterized by high suicide rates. Recent analyses indicate a possible association of antidepressant treatment and suicidality in children and adults with depressive or anxiety disorders. However, few data are available to inform the suicidality risk assessment of antidepressant use specifically in bipolar disorder.

Method: Of the first 2000 participants followed for 18 months in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), 425 experienced a prospectively observed, new-onset major depressive episode without initial suicidal ideation. Standardized ratings of suicidality and antidepressant exposure at index depressive episode and next evaluation were used to investigate the primary hypothesis that new-onset suicidality was associated with increased antidepressant exposure (antidepressant initiation or dose increase). Secondary analysis investigated correlates of new-onset suicidality and antidepressant exposure. Data were collected from November 8, 1999, to April 24, 2002.

Results: Twenty-four participants (5.6%) developed new-onset suicidality at follow-up, including 2 suicide attempts. There was no association of new-onset suicidality with increased antidepressant exposure or any change in antidepressant exposure, and no association with initiation of antidepressant treatment. New-onset suicidality was associated with neuroticism, prior attempt, and higher depressive or manic symptom ratings at index episode. Increased antidepressant exposure was negatively associated with higher manic symptom rating at index episode; control for this sole empirically identified confound did not alter the primary results.

Conclusions: Although careful monitoring for suicidality is always warranted in bipolar disorder, this cohort study provides no evidence that increased antidepressant exposure is associated with new-onset suicidality in this already high-risk population. Correlates of both suicidality and antidepressant exposure indicate directions for further research.