Two ketamine doses worked similarly across depression, PTSD, anxiety and OCD

The question

Does a higher dose of ketamine work better than a lower dose for so-called internalizing disorders, and how long do any effects last?

What they did

Researchers re-analyzed data from trials in people with treatment-resistant depression, post-traumatic stress disorder, generalized and/or social anxiety, or obsessive-compulsive disorder. Each person received single injections into a muscle of racemic ketamine at 0.5 mg/kg and at 1.0 mg/kg, plus a psychoactive comparison drug, in a cross-over design where everyone tried all three conditions in a randomized, double-blind order (neither participants nor raters knew which was which). Symptoms were rated with scales matched to each diagnosis.

What they found

Both ketamine doses produced large improvements on the symptom scales for every disorder studied compared with the psychoactive control. The effects were clearest 24 hours after dosing and noticeably smaller by 168 hours (one week). The 1.0 mg/kg dose did not differ significantly from 0.5 mg/kg at either time point, and the size of the response at 24 hours did not differ significantly between the different disorders. The authors suggest ketamine may follow a narrow inverted-U dose-response curve peaking somewhere around 0.5-1.0 mg/kg.

The fine print

This is a secondary analysis, meaning the comparison was not the trials’ original main question. The abstract does not report the number of participants, the exact effect sizes, or the safety findings. Ketamine’s noticeable psychoactive effects can make blinding imperfect, even with an active comparison drug. Follow-up in the reported results extended only to one week, and this summary is based on the abstract alone.

What it means

In these trials, doubling the ketamine dose did not produce a bigger symptom improvement, and benefits faded substantially within a week.

Evidence grade: Low. This is a secondary analysis of trial data, and the abstract does not report how many people took part.

This summary is based on the study’s published abstract.