Evidence by molecule
How strong the research is for each treatment, on our four-level evidence scale. Each links to the full molecule guide.
Pooled data from 10 trials (167 people) show a drop in suicidal thoughts within one day, lasting up to a week. Long-term effects on suicide risk are unknown.
Two phase 3 trials (226 and 230 people) found faster improvement in depression within 24 hours. Neither found a significant difference from placebo on the measure of suicidality.
What the research shows
Ketamine. An analysis pooling individual data from 167 people across ten trials found that a single ketamine infusion reduced suicidal thoughts within one day compared with control treatments, with effects lasting up to a week.1 See our ketamine guide.
Esketamine. Two phase 3 trials, ASPIRE I and II (226 and 230 people), enrolled adults hospitalised with depression and active suicidal thoughts. Esketamine plus standard care improved depression faster than placebo plus standard care. But in both trials, the difference on the suicidality measure itself wasn’t statistically significant.23 See our esketamine guide.
Psilocybin. In the largest psilocybin depression trial, suicidal thoughts, suicidal behaviour or self-harm occurred in every dose group. That’s a reminder that people in these trials need close monitoring.4
Established treatments
Crisis support, safety planning, psychotherapies and treatment of underlying conditions all play a role. Anyone having suicidal thoughts should reach out to a qualified health professional or a crisis line.
Studies in the library
- Ketamine eased "psychological pain" for up to 4 days in suicidal inpatientsRCT · 2026 · Evidence: Low
- Review of 11 studies on non-medical psychedelic use and suicidal thoughtsSystematic review · 2026 · Evidence: Low
- Review of newer treatments for suicidal thoughts finds ayahuasca among promising optionsOther · 2026 · Evidence: Low
- A review proposing two routes for turning ibogaine into a medicineSystematic review · 2026 · Evidence: Very low
- Pooled analysis of 26 trials: IV ketamine rapidly lowers depression and suicidal symptomsMeta-analysis · 2026 · Evidence: Moderate
- Morning cortisol rose 24 hours after ketamine in a trial for suicidal depressionRCT · 2026 · Evidence: Low
- Pilot trial tests whether a ketamine study is feasible for teens in the emergency departmentRCT · 2026 · Evidence: Very low
- Low-dose buprenorphine after a ketamine infusion and suicidal thoughts in depressionRCT · 2026 · Evidence: Moderate
- Single dose of psilocybin in 20 adults with chronic suicidal thoughts: open-label trialOpen-label trial · 2026 · Evidence: Low
- Review: IV ketamine for treatment-resistant depression showed no cognitive declineSystematic review · 2026 · Evidence: Low
- Adding CBT to esketamine for depression with suicidal thoughts: a randomized trialRCT · 2026 · Evidence: Moderate
- Systematic review: ayahuasca and suicidal thoughts in hard-to-treat depressionSystematic review · 2026 · Evidence: Low
- Esketamine and suicidal thoughts in treatment-resistant depression, with and without borderline PDObservational · 2026 · Evidence: Low
- Pilot trial of a single ketamine infusion for teens with suicidal thoughts in the ERRCT · 2026 · Evidence: Very low
- Esketamine nasal spray in routine care: 50 patients with treatment-resistant depression trackedObservational · 2026 · Evidence: Low
- Brain scan markers that may predict who responds to ketamine for depressionSystematic review · 2026 · Evidence: Low
- Which patients respond best to ketamine for suicidal thoughts? A post-hoc analysis of 67 peopleOther · 2026 · Evidence: Low
- Esketamine infusions did not change inflammation markers in depressed teensRCT · 2026 · Evidence: Low
- Ketamine vs. electroconvulsive therapy for severe depression with suicidal thoughtsRCT · 2026 · Evidence: Moderate
- Ketamine vs midazolam for suicidal thoughts: pooled results from 10 randomized trialsMeta-analysis · 2026 · Evidence: Moderate
- Review of 21 studies: ketamine linked to large short-term drops in suicidal thinkingMeta-analysis · 2026 · Evidence: Moderate
- Esketamine's effect on suicidal thoughts appears tied to its effect on depressionObservational · 2026 · Evidence: Low
- Pilot study of a single nasal ketamine dose for acute suicidal thoughts in 12 patientsOpen-label trial · 2025 · Evidence: Very low
- Thyroid hormone levels linked to ketamine response in bipolar depression, not major depressionRCT · 2025 · Evidence: Low
- Review of brain markers linked to reduced suicidal thoughts, including with IV ketamineSystematic review · 2025 · Evidence: Low
- Ketamine for teen depression: pooled trials show no clear mood benefit at 24 hoursMeta-analysis · 2025 · Evidence: Moderate
- Ketamine and esketamine for hard-to-treat depression in youth: a review of the evidenceSystematic review · 2025 · Evidence: Low
References
- Wilkinson ST, et al. The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis. American Journal of Psychiatry. 2018;175(2):150–158. Source
- Fu DJ, et al. Esketamine nasal spray for rapid reduction of major depressive disorder symptoms in patients who have active suicidal ideation with intent (ASPIRE I). Journal of Clinical Psychiatry. 2020;81(3):19m13191. Source
- Ionescu DF, et al. Esketamine nasal spray for rapid reduction of depressive symptoms in patients with major depressive disorder who have active suicide ideation with intent (ASPIRE II). International Journal of Neuropsychopharmacology. 2021;24(1):22–31. Source
- Goodwin GM, et al. Single-dose psilocybin for a treatment-resistant episode of major depression. New England Journal of Medicine. 2022;387(18):1637–1648. Source
- Government of Canada. 9-8-8: Suicide Crisis Helpline. Source