Antidepressants and Mood Switching in Bipolar Disorder

Nearly one in three bipolar patients switched to mania or hypomania on antidepressants

STUDY: Miola A et al, Journal of Affective Disorders 2026;408:121849

STUDY TYPE: Prospective observational cohort study

FUNDING: Aretaeus Foundation of Rome; Bruce J. Anderson Foundation; McLean Private Donors Psychiatric Research Fund

Background

This large prospective trial from Italy clarifies which clinical features predict antidepressant-induced switching in bipolar disorder.

The Study

• 1,629 adults with bipolar disorder (913 type I, 716 type II)
• Followed for an average of five years while treated with antidepressants
• The primary outcome = any new episode of mania or hypomania during antidepressant treatment

Mood switching occurred in 27.6% of patients overall, equal in men and women and slightly more often in bipolar II (31.4%) than bipolar I (24.5%). Most switches (65.5%) were into hypomania rather than full mania.

Five factors independently predicted switching in the multivariate model:

• DMI illness course (depressions that are followed by mania) (odds ratio 9.69)
• Older age (odds ratio 1.04 per year)
• More episodes per year (odds ratio 1.26)
• Family history of psychiatric illness (odds ratio 1.94)
• History of suicide attempts (odds ratio 1.57)

Antidepressant type (tricyclics versus SSRIs) did not significantly predict switching in this dataset, though the trend pointed to tricyclics, and other studies point that way as well.

Limitation: The study cannot prove causation, as it is difficult to distinguish antidepressant-induced switching from spontaneous mood shifts.