Immediate and Persistent Antidepressant Effects of Repeated Ketamine Infusions in Treatment-Resistant Major Depression


Ketamine is recognized for its rapid antidepressant effects, yet little is known about its impact beyond a single infusion. A previous study involving 10 individuals with treatment-resistant major depression (TRD) indicated that six ketamine infusions resulted in sustained antidepressant effects. In this updated report, we investigate the pattern and durability of these effects in a larger sample, including participants from the original study.

Methods: Twenty-four participants with TRD underwent a washout of antidepressant medication followed by up to six intravenous infusions of ketamine (0.5 mg/kg), administered openly three times weekly over a 12-day period. Those showing a positive response were monitored for relapse up to 83 days post-infusion.

Results: By the study’s conclusion, the overall response rate was 70.8%. Significant reductions in Montgomery–Asberg Depression Rating Scale (MADRS) scores were observed as early as two hours after the first ketamine infusion (18.9±6.6, p<0.001), with sustained decreases throughout the infusion period. Response at study end strongly correlated with response at four hours (94% sensitive, 71% specific). Among responders, the median time to relapse post-infusion was 18 days.

Conclusions: Ketamine demonstrated rapid antidepressant effects in TRD that persisted over time. Future controlled studies are necessary to devise strategies for maintaining antidepressant responses in patients benefiting from ketamine therapy.

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