Recent systematic review of clinical trials since 2020 has revealed promising developments in the use of ketamine and its enantiomers for treating suicidal ideation (SI), offering new hope in acute psychiatric care.
Efficacy Across Different Administration Routes
Intravenous (IV) ketamine has emerged as the most effective delivery method, with six out of eight studies showing significant anti-suicidal effects. In a notable double-blind trial involving 156 participants, ketamine treatment led to significantly higher SI remission rates compared to placebo (95% CI; 1.9 to 7.3, P < 0.001) by day three.
Intranasal administration, while showing promise, demonstrated more modest results. The Janssen Phase 3 trials of intranasal S-ketamine, involving over 450 adults with major depressive disorder (MDD) and acute SI, showed improvements in depressive symptoms but variable effects on suicidal ideation. Notably, patients with previous suicide attempts showed better responses to the treatment.
Duration and Dosing Considerations
Multiple-dose regimens appear to offer superior outcomes compared to single administrations. While single-dose effects typically waned within 3-7 days, multiple doses maintained anti-suicidal benefits for periods ranging from two days to six weeks. This finding suggests the potential need for maintenance treatment protocols.
A particularly significant study comparing intramuscular ketamine with electroconvulsive therapy (ECT) in 45 adults with MDD found that ketamine showed comparable or superior anti-suicidal effects at two weeks (p = 0.033), challenging traditional treatment hierarchies.
Safety Profile and Future Directions
The safety profile remains consistent with previous research, with most adverse effects being transient and resolving within 24 hours. Common side effects include dissociation, dizziness, hypertension, and nausea, but these are generally well-tolerated by patients.
Emerging research on R-ketamine shows particular promise, with preliminary studies indicating fewer psychomotor side effects compared to other formulations. However, larger randomized controlled trials are still needed to definitively establish its efficacy in humans.
Clinical Implications
Treatment response appears to be influenced by several factors, including:
- Duration of current depressive episode
- Number of prior failed antidepressant trials
- Presence of bipolar disorder
- Cognitive function at baseline
These findings underscore the importance of personalized treatment approaches and careful patient selection.
Research Gaps and Future Needs
While current evidence supports ketamine's role in rapid SI reduction, several important questions remain unanswered. Larger studies are needed to:
- Evaluate long-term safety profiles
- Determine optimal dosing strategies for specific populations
- Assess efficacy in adolescent populations
- Study potential effects on actual suicidal behavior
The field particularly needs additional research on adolescent populations, given that suicide ranks as the fourth leading cause of death worldwide in this age group.
