Ketamine for Bipolar Depression: A Systematic Review

Abstract

Background Ketamine appears to have a therapeutic role in certain mental disorders, most notably unipolar major depressive disorder. However, its efficacy in bipolar depression is less clear. This study aimed to assess the efficacy and tolerability of ketamine for bipolar depression. Methods We conducted a systematic review of experimental studies using ketamine for the treatment of bipolar depression. We searched PubMed, MEDLINE, Embase, PsycINFO, and the Cochrane Central Register for relevant studies published since each database’s inception. We synthesized evidence regarding efficacy (improvement in depression rating scores) and tolerability (adverse events, dissociation, dropouts) across studies. Results We identified 6 studies, with 135 participants (53% female; 44.7 years; standard deviation, 11.7 years). All studies used 0.5 mg/kg of add-on intravenous racemic ketamine, with the number of doses ranging from 1 to 6; all participants continued a mood-stabilizing agent. The overall proportion achieving a response (defined as those having a reduction in their baseline depression severity of at least 50%) was 61% for those receiving ketamine and 5% for those receiving a placebo. The overall response rates varied from 52% to 80% across studies. Ketamine was reasonably well tolerated; however, 2 participants (1 receiving ketamine and 1 receiving placebo) developed manic symptoms. Some participants developed significant dissociative symptoms at the 40-minute mark following ketamine infusion in 2 trials. Conclusions There is some preliminary evidence supporting use of intravenous racemic ketamine to treat adults with bipolar depression. There is a need for additional studies exploring longer-term outcomes and alterative formulations of ketamine.

Association of intranasal esketamine, a novel ‘standard of care’ treatment and outcomes in the management of patients with treatment-resistant depression: protocol of a prospective cohort observational study of naturalistic clinical practice

“…However, most of the evidence about racemic ketamine focuses on intravenous administration which could deter some patients. 6 Nevertheless, it is important to note that despite the higher affinity of esketamine for the NMDA receptor, some studies have raised concerns about the use of esketamine over racemic ketamine, namely the presence of dissociative symptoms with similar intensities between the two treatments and the cost of the esketamine treatment. [11][12][13] The extant clinical research has resulted in the approval of this treatment by the US Food and Drug Administration (FDA) and Health Canada, among other regulatory agencies, for the management of TRD.…”

“…2 3 Low-dose ketamine treatments have demonstrated significant effectiveness in the management of treatment-resistant depression (TRD) in MDD and bipolar depression. [4][5][6] Ketamine acts by blocking the NMDA receptor and thus triggering a series of downstream effects that promote neuroplasticity and neurogenesis. 4 7 8 Esketamine is the S-enantiomer of ketamine and possesses an affinity for the NMDA receptor that is around fourfold stronger than the affinity of the other enantiomer…”

Ketamine for Bipolar Depression: Biochemical, Psychotherapeutic, and Psychedelic Approaches

“…It is generally well tolerated and has a short half-life, which translates into fewer side effects than traditional antidepressant medications. Most of the existing research to date on the use of racemic ketamine for depression (unipolar and bipolar) has looked at a sub-psychedelic dose of ketamine given by infusion as a stand-alone treatment, without concurrent psychotherapy [See ( 8 ) for a meta-analysis of previous research studies].…”

Efficacy and Tolerability of Two Novel “Standard of Care” Treatments—Intranasal Esketamine Versus Intravenous Ketamine—for Treatment-Resistant Depression in Naturalistic Clinical Practice: Protocol for a Pilot Observational Study

“…Racemic ketamine and its enantiomer esketamine have been studied as novel alternatives for treatment-resistant depression (TRD) in major depressive disorder (MDD) and bipolar depression [ 1 - 3 ]. Studies with intravenous (IV) racemic ketamine have demonstrated rapid and potent reduction of depressive symptoms after the administration of a single subanesthetic dose (response rate=3.01, 95% CI 1.96-4.62; remission rate=3.70, 95% CI 2.28-6.01) [ 4 - 8 ].…”