Ketamine for Depression: Adverse Effects Are Mild and Brief

Researchers find the adverse effects of ketamine are mild enough for use, amid controversial concerns.


A single subanesthetic dose of ketamine infusion can often relieve depressive symptoms within hours when conventional antidepressants have not worked. But off-label use of IV ketamine—especially given its history of abuse—has raised concerns about adverse effects (AEs).

However, a single low-dose infusion was “relatively free of side effects” for patients with treatment-resistant depression, according to researchers from the National Institute of Mental Health. They compiled data on AEs from 163 patients with major depressive disorder or bipolar disorder and 25 healthy controls from 5 placebo-controlled crossover clinical trials and 1 open-label study conducted at the National Institutes of Health (NIH) Clinical Center over 13 years.

The assessments included active and structured surveillance of emerging AEs in an inpatient setting and used both a rating scale and clinician interviews.

The most common effect was feeling “strange or loopy,” the researchers say. Most AEs peaked within an hour of administration and were gone within 2 hours. The researchers did not see any serious, drug-related AEs or increased ketamine cravings.

The researchers evaluated 120 possible AEs. Of the 44 that occurred in at least 5% of participants over all trials, 33 were significantly associated with treatment. At least half the participants reported the “spacey” feeling, visual distortions, difficulty speaking, and numbness. No AEs lasted beyond 4 hours.

The study did not address AEs associated with repeated infusions or long-term use, but during the approximately 3-month follow-up period, the researchers found no drug-related serious AEs, propensity for recreational use, or significant cognitive or memory deficits.

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