Ketamine for the treatment of mental health and substance use disorders: comprehensive systematic review
Summary & key facts
This paper looked through the available human studies to see how ketamine works for mental health problems. The authors collected about 80 reports, including careful reviews and many clinical trials. They found good evidence that low doses of ketamine can lift depression symptoms and reduce suicidal thoughts quickly, but the effects usually do not last long. For other mental health problems the results are less clear. The studies had many weaknesses, so the authors say we need better trials to figure out the best dose, how to give ketamine, and whether combining it with therapy helps.
- The team reviewed human studies and registered their plan ahead of time so the search was organized and planned.
- They included about 80 published reports. These were a mix of careful reviews and different types of clinical trials.
- Reviews and combined analyses show that low doses of ketamine can produce a strong and fast antidepressant effect.
- The same high-quality summaries also support a quick reduction in suicidal thoughts after ketamine, but this change is usually short-lived.
- For other conditions besides depression, the evidence is weaker, but some studies show brief benefits.
- Many of the included studies had a high risk of bias, meaning their results might be unreliable or overstated.
- Because of those weaknesses, the authors say more research is needed on the right dose, the best way to give ketamine, and how to add psychotherapy to treatment.
Abstract
BACKGROUND: In the past two decades, subanaesthetic doses of ketamine have been demonstrated to have rapid and sustained antidepressant effects, and accumulating research has demonstrated ketamine's therapeutic effects for a range of psychiatric conditions. AIMS: In light of these findings surrounding ketamine's psychotherapeutic potential, we systematically review the extant evidence on ketamine's effects in treating mental health disorders. METHOD: The systematic review protocol was registered in PROSPERO (identifier CRD42019130636). Human studies investigating the therapeutic effects of ketamine in the treatment of mental health disorders were included. Because of the extensive research in depression, bipolar disorder and suicidal ideation, only systematic reviews and meta-analyses were included. We searched Medline and PsycINFO on 21 October 2020. Risk-of-bias analysis was assessed with the Cochrane Risk of Bias tools and A Measurement Tool to Assess Systematic Reviews (AMSTAR) Checklist. RESULTS: We included 83 published reports in the final review: 33 systematic reviews, 29 randomised controlled trials, two randomised trials without placebo, three non-randomised trials with controls, six open-label trials and ten retrospective reviews. The results were presented via narrative synthesis. CONCLUSIONS: Systematic reviews and meta-analyses provide support for robust, rapid and transient antidepressant and anti-suicidal effects of ketamine. Evidence for other indications is less robust, but suggests similarly positive and short-lived effects. The conclusions should be interpreted with caution because of the high risk of bias of included studies. Optimal dosing, modes of administration and the most effective forms of adjunctive psychotherapeutic support should be examined further.
