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Bipolar Disorder / Depression · Journal article
Journal of Affective Disorders · August 10, 2026
Encouraging direction, but not yet definitive.
This secondary analysis of a 6-week RCT demonstrates that intravenous ketamine (0.5 mg/kg) produced greater reduction in self-rated psychological pain than placebo in suicidal inpatients during the acute phase (40 min to 96 h), with the largest differences at 40 min, 2 h, 4 h, and 24 h (all p < 0.001). However, the effect was not sustained beyond 96 hours, and no differences were observed at weeks 2, 4, or 6 post-infusion. Psychological pain is a proposed mechanistic pathway to suicidality but is not a validated clinical outcome.
Randomized, double-blind, placebo-controlled trial (secondary analysis). Suicidal psychiatric inpatients enrolled in the KETIS trial; setting not explicitly stated but indicates inpatient psychiatric facility.. Intervention: Two 40-minute intravenous infusions of ketamine 0.5 mg/kg, 24 hours apart, plus usual care and medication. Compared with: Two 40-minute intravenous infusions of 0.9% saline placebo, 24 hours apart, plus usual care and medication. n = 156.
Psychological pain decreased in both ketamine (n=73) and placebo (n=83) groups, but was lower with ketamine from 40 min to 96 h (all p < 0.001) Largest pointwise differences at 40 min, 2 h, 4 h, and 24 h post-infusion (all p < 0.001) No significant differences between ketamine and placebo at weeks 2, 4, or 6
Safety was not reported in the material analysed. Check the source before drawing any conclusion about harm.
Clinicians should note that ketamine may provide rapid, acute relief of psychological pain in suicidal inpatients within hours of administration, which could have value in crisis settings. However, the absence of sustained benefit beyond 96 hours and lack of evidence for impact on hard clinical outcomes (e.g., suicide attempts, completion) limit current clinical application pending further research on clinical outcomes.
A double-blind RCT with adequate sample size and pre-specified primary endpoint shows ketamine reduces psychological pain acutely in suicidal inpatients, but effects do not persist beyond 96 hours and the clinical significance of this surrogate outcome remains unclear.
As stated by the source record.
Quoted from the source exactly as published.
Clinicians should note that ketamine may provide rapid, acute relief of psychological pain in suicidal inpatients within hours of administration, which could have value in crisis settings. However, the absence of sustained benefit beyond 96 hours and lack of evidence for impact on hard clinical outcomes (e.g., suicide attempts, completion) limit current clinical application pending further research on clinical outcomes.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Background. Psychological pain has been conceptualized as an unbearable inner experience and a possible precondition for suicidal ideation. No randomized placebo-controlled study has specifically investigated psychological pain as a treatment target in psychiatric populations. We examined ketamine's effect on psychological pain in suicidal psychiatric inpatients.Methods. This secondary analysis used KETIS, a 6-week randomized, double-blind, placebo-controlled trial. Participants received two 40-minute intravenous infusions of ketamine (0.5 mg/kg) or placebo (0.9% saline) 24 h apart, alongside usual care and medication. Psychological and physical pain were assessed at baseline, repeatedly during 96 h, and at weeks 2, 4, and 6 using the self-rated PPP-VAS. Longitudinal mixed models compared pain trajectories.Results. The trial randomized suicidal inpatients to ketamine (n = 73) or placebo (n = 83). Psychological pain decreased in both groups but was lower with ketamine during the first 96 h. Pointwise scores were lower with ketamine from 40 min to 96 h, largest at 40 min, 2 h, 4 h, and 24 h (all p < 0.001), but not at weeks 2, 4, or 6. This early difference remained significant after adjustment for depressive symptoms and hopelessness. The early reduction appeared more pronounced in the bipolar subgroup. No robust baseline predictors of outcome were identified.Conclusions. Intravenous ketamine was associated with a greater reduction in psychological pain than placebo in suicidal inpatients, with the clearest effects emerging within the first hours after treatment and remaining evident through the first 96 h. Ketamine may represent a clinically relevant option as a psychological pain reliever in psychiatric patients.
Taken from the source record, never inferred. Follow any of these and new work involving them reaches your briefing.