Depression and Anxiety
August 19, 2023
Anna J. Harvey, Stevan Nikolin, Nicholas Chand et al.
4 citations
A single dose of ketamine, compared to an active control (midazolam), did not produce significant changes in most measures of emotional or cognitive processing in people with treatment-resistant depression one day after treatment. However, participants who received ketamine showed a significant improvement on a test of negative processing bias, though this improvement was not significantly linked to changes in depressive symptoms. The study was small and exploratory, and larger trials are needed to confirm the finding.
The British journal of psychiatry : the journal of mental science
January 7, 2025
Natalie T Mills, Stevan Nikolin, Nick Glozier et al.
3 citations
Anxiety disorders and treatment-resistant major depressive disorder (TRD) often occur together. In a randomized controlled trial comparing subcutaneous ketamine to midazolam in 174 people with TRD, ketamine reduced anxiety only when given at flexible, response-guided doses (0.5-0.9 mg/kg). At a fixed low dose (0.5 mg/kg), the reduction in anxiety was not statistically significant. The anxiety-reducing effect was linked to overall depression improvement and was not sustained four weeks after treatment ended. The findings suggest that adequate dosing is necessary for ketamine's anxiolytic effect in this population.
Translational psychiatry
January 23, 2026
Stevan Nikolin, Clara Massaneda-Tuneu, Louise Brettell et al.
1 citation
Electroconvulsive therapy (ECT) leads to a faster reduction in depressive symptoms than ketamine for severe, medication-resistant depression. A meta-analysis of seven studies with 731 participants found that depression scores were slightly lower at baseline in the ketamine group. After adjusting for baseline differences, ECT produced an additional improvement of about 0.02 standardized mean difference per day, amounting to a predicted moderate advantage over ketamine after four weeks. This advantage falls within the range considered clinically meaningful.
The British Journal of Psychiatry
July 6, 2026
Nick Glozier, Richard W. Morris, Elizabeth Stratton et al.
A 4-week course of subcutaneous racemic ketamine produced short-term clinical benefit in a minority of people with treatment-resistant depression, with response rates declining substantially after treatment cessation. Among 130 participants, 30% responded at treatment end (Montgomery-Åsberg Depression Rating Scale reduction ≥50%), but only 17% remained responders 4 weeks later, and over 50% experienced less than a 25% reduction in depression scores. No difference in response was found between fixed and flexible dosing regimens. Prior ketamine treatment during an earlier randomized trial did not affect later outcomes. No suicides or suicidal behavior requiring admission occurred, and only expected side effects were observed.
Archives of suicide research : official journal of the International Academy for Suicide Research
May 9, 2026
Gregory Carter, Maree Hackett, Stevan Nikolin et al.
Ketamine's effect on suicidal ideation in adults with treatment-resistant depression remains uncertain. In a phase III double-blind randomized trial comparing subcutaneous racemic ketamine to midazolam over four weeks, one cohort showed no significant difference between groups on either the MADRS item 10 or the C-SSRS measure of suicidal ideation. A second cohort showed a non-significant reduction on the MADRS item 10 but a significant reduction on the C-SSRS. Baseline suicidal ideation scores were low in both cohorts. Adverse events requiring clinical review occurred in 13.8% of all treatment sessions. The authors suggest flexible-dose subcutaneous racemic ketamine may have beneficial effects on suicidal ideation scores, but future studies need to be powered for suicidal ideation as a primary outcome.