One of the most promising uses of ketamine in the mental health field is to treat Major Depression Disorder. In 2000, a controlled study1 by Dr. Robert M. Berman and colleagues evaluated ketamine infusions for the treatment of seven individuals with MDD. Researchers reported significant reductions in depressive symptoms within 72 hours of ketamine treatment. This early study led to later research that confirmed the efficacy of ketamine for the rapid reduction of depression symptoms.
A 2014 review and meta-analysis2 of randomized, double-blind, placebo-controlled trials on the effects of intravenous and nasal ketamine in the treatment of MDD found ketamine to be efficacious in rapidly reducing symptoms with a sustained response for up to two weeks following treatment. Researchers reviewed eight randomized double-blind trials that included 149 participants with MDD and 34 participants with bipolar depression. The researchers found significant clinical remission at one, three, and seven days following a single treatment.
Another meta-analysis from 20153 reviewed data from three clinical trials, conducted between 2006 and 2012, that included 205 intravenous ketamine infusions (0.5 mg over 40 minutes) in 97 participants with MDD. The overall response rate was 67 percent across all participants. Researchers found that the effects of treatment were relatively well-tolerated, with no persistent psychotomimetic or adverse effects or increased substance use among participants.
Further reviews of completed studies continue to suggest that ketamine is novel in how fast-acting and effective it can be for therapeutic use. A 2017 review analyzed4 12 trials—a mix of randomized clinical trials and open-label trials—that included 226 participants with MDD who were treated with intravenous or intranasal ketamine. Findings indicated a significant reduction in symptoms and found that ketamine was superior to placebo. Researchers concluded that with a 61 percent response rate after 24 hours. According to the review, “ketamine constitutes a novel, rapid and efficacious treatment option for patients suffering from treatment resistant depression and exhibits rapid and significant anti-suicidal effects.”
Studies also suggest that serial ketamine infusions are an effective treatment for TRD, producing rapid antidepressant effects which generally last between two and four weeks.
In a 2012 open-label study5 , researchers investigated the effects of six ketamine infusions over a 12-day period on 24 people with TRD who had discontinued antidepressant medication6 . The response rate was over 70 percent at treatment completion. Median time to relapse was 18 days after the last ketamine session. The researchers found that serial ketamine infusions produced a rapid antidepressant effect in TRD patients.
Another open-label study7 from 2013 involving 14 participants with TRD examined the effects of six serial ketamine infusions (0.5mg on Mondays, Wednesdays, and Fridays) over a 12-day period. Out of the 12 participants who completed the treatment protocol, 66 percent of participants achieved remission by the end of the treatment with approximately 92 percent responding to the treatment. Five participants maintained response status throughout the four weeks of follow-up, while six participants relapsed within four weeks.
In 20168 , a double-blind, randomized, placebo-controlled, dose-frequency study evaluated intravenous ketamine used on 67 TRD patients (including 45 women). IV ketamine was administered at 0.5mg two or three times per week. Both dosage levels produce rapid-onset and sustained antidepressant effects for a 15-day period.
