Bipolar disorder: Systematic review of approved psychiatric medications (2008-2024) and pipeline Phase-3 medications

This systematic review evaluates psychiatric medications for bipolar disorder (BP) approved by the U.S. FDA between 2008 and 2024, alongside investigational agents in advanced clinical development, in addition to medications with exploratory evidence. It categorizes these treatments by clinical relevance, mechanism of action, efficacy, dosing, adverse effects, and guideline and real-world use.

We conducted a systematic search of PubMed, FDALabel, and ClinicalTrials.gov databases for studies published between 2008 and 2024, using keywords including "bipolar" AND "psychopharm*" OR "medic*" OR "pharm*." Two reviewers independently assessed the resulting publications, resolving any discrepancies through consensus to finalize the studies for inclusion in this review. Key findings from the selected full-text articles were extracted to compile data for the review tables. We also utilized practice guidelines for BP from the US, Canada, the UK, and Australia/New Zealand.

BP medications were categorized into three tiers: (1) FDA-approved and guideline-endorsed, (2) FDA-approved, with emerging clinical use, and (3) Phase 3 agents. We described eight Tier 1 and eight Tier 2 medications that received FDA approval from 2008 to 2024, seven that are actively in pipeline Phase 3 clinical trials, and six more medications with exploratory evidence.

Advances in pharmacologic treatment for bipolar disorder over the past 16 years reflect a shift towards individualized, mechanism-based care. Our tiered framework offers clinicians and researchers a structured approach to evaluate treatment maturity and real-world applicability. Continued research and careful interpretation of the evolving pipeline and medications with exploratory evidence are essential to optimize long-term management.