New Pharmacologic Approaches to the Treatment of Bipolar Depression.
Kamyar Keramatian, Trisha Chakrabarty, Anais DuBow, Gayatri Saraf, Lakshmi N. Yatham
Drugs July 1, 2023 DOI: 10.1007/s40265-023-01872-x (opens in new tab)
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Study at a glance
AI-extracted from the abstract| Characteristics | Review Randomized Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Population | Individuals with bipolar disorder |
| Interventions | Lumateperone Cariprazine Non-racemic amisulpride Ketamine Cycloserine Lurasidone Zuranolone Anti-inflammatories Mitochondrial modulators Cannabidiol Psilocybin |
| Topics | Depression |
| Keywords | Mental-health Psychiatric-treatment Bipolar-disorder Depression-therapy Medical-research |
| Citations | 19 |
| Key findings | New atypical antipsychotics lumateperone and cariprazine have demonstrated efficacy in large placebo-controlled trials for bipolar depression, while intravenous ketamine shows rapid effects in small studies, but many emerging agents require further validation. |
Abstract
Depression is the most commonly experienced mood state over the life span in individuals with bipolar disorder (BD) and is the primary driver of functional impairment and suicidality in BD. Despite this, there are few effective treatments for BD depression, with only a handful of atypical anti-psychotics and inconsistent evidence for traditional mood stabilizing agents. There have been few major 'breakthroughs' in the treatment of BD depression, and until recently, few agents that work via novel mechanisms of action to exert therapeutic effects. Here, we review treatments for BD depression which are emergent or on the horizon. Included are new atypical anti-psychotics, glutamate modulators (ketamine and cycloserine/lurasidone), neurosteroid modulators (zuranolone), anti-inflammatories and mitochondrial modulators, cannabidiol (CBD) and psilocybin. New atypical anti-psychotics lumateperone and cariprazine have demonstrated efficacy in large-scale, placebo-controlled, double-blind randomized controlled trials (RCT) in treatment of BD depression. Non-racemic amisulpride showed potential therapeutic benefit in one RCT which requires replication. Three small RCTs examined the efficacy of intravenous ketamine in BD depression and showed rapid antidepressant and anti-suicidal effects after a single infusion. Anti-inflammatory and mitochondrial modulators show inconsistent evidence for efficacy. There are currently no adequately powered RCTs of zuranolone, psilocybin or CBD in BD depression to support their use. While there are potentially efficacious, mechanistically novel agents on the horizon, they require further study and validation. Further investigation on how these agents may impact specific subgroups of patients will also advance the field.
Comparable studies
Other narrative reviews on depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Synaptic Dysfunction in Depression: Potential Therapeutic Targets | 2012 | Review | |
| Mindfulness-Based Cognitive Therapy for Depression: A New Approach to Preventing Relapse | 2003 | Review | |
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. General population | 2019 | Integrative review | |
| Sudarshan Kriya Yogic Breathing in the Treatment of Stress, Anxiety, and Depression: Part II—Clinical Applications and Guidelines | 2005 | Review |
Citations in the library
Cited by 3
- New Agents in the Treatment of Psychiatric Disorders: What Innovations and in What Areas of Psychopathology? Pharmaceuticals April 30, 2025
- Nonresponse to Ketamine in Treatment‐Resistant Bipolar Depression Neuropsychopharmacology Reports July 20, 2025
- Next-Generation Pharmacotherapy for Depressive Disorders: From Novel Compounds to Optimized Use of Available Drugs. Drug Design, Development and Therapy 2026
Cites 13
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
- A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression Archives of General Psychiatry August 1, 2010
and 8 more in the library