Short Term Second-Generation Antidepressant Monotherapy in Acute Depressive Episodes of Bipolar II Disorder: A Systematic Review and Meta-Analysis

Jin Hong Park, Nicolas A. Nuñez, Manuel Gardea-Resendez, Danielle J. Gerberi, Scott Breitinger, Marin Veldic, Mark A. Frye, Balwinder Singh

Research output: Contribution to journalArticlepeer-review


Purpose: Bipolar II disorder (BD-II) has limited evidence-based treatment guidelines. The aim of this systematic review and meta-analysis was to estimate the efficacy and safety of second-generation antidepressant (SGAD) monotherapy in acute BD-II depression. Methods: A literature search was conducted from the database inception through March 2021. Only randomized controlled trials (RCTs) were included. Outcome measures included: response rates, treatment-emergent affective switch (TEAS) rates, discontinuation due to side-effects, and all-cause discontinuation. Risk ratio (RR) was calculated using the Mantel-Haenszel random effects model. Results: 3301 studies were screened, and 15 articles were selected for full-text review. Five studies met the inclusion criteria: Four double-blind RCTs (n = 533) and one open-label RCT (n = 83) were included. Two double-blind RCTs [n = 223, SGAD = 110 (venlafaxine = 65, sertraline = 45), lithium/control = 113] were included for meta-analysis. The response rate for SGAD monotherapy compared to lithium monotherapy were similar (RR = 1.44, 95% CI 0.78, 2.66). The TEAS rate for SGAD monotherapy was not significantly different from lithium monotherapy (p = 0.76). The discontinuation rate due to side-effects for SGAD monotherapy was significantly lower than lithium monotherapy with a RR = 0.32, 95% CI 0.11, 0.96, p = 0.04 but all-cause discontinuation rates were similar in both groups. Conclusions: Limited data suggests short-term efficacy of venlafaxine and sertraline monotherapy in patients with acute BD-II depression with good side effect tolerability and without significantly increased switch rate. There is an urgent need for RCTs investigating the role of SGAD monotherapy in short and long-term among patients with BD-II.

Original languageEnglish (US)
Pages (from-to)45-72
Number of pages28
JournalPsychopharmacology bulletin
Issue number2
StatePublished - May 31 2022


  • antidepressants
  • bipolar II disorder
  • bipolar depression
  • meta-analysis

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology (medical)


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