Registered clinical trials investigating ketamine for psychiatric disorders.

As interest has grown in the potential psychiatric applications of ketamine, the number of registered clinical trials has grown substantially. Herein, we summarize and analyze clinical trials registered with ClinicalTrials.gov that assess the treatment of any psychiatric disorder with ketamine or ketamine enantiomers (e.g., S-ketamine, R-ketamine), with a focus on ongoing clinical trials. A ClinicalTrials.gov search on February 21, 2020 returned 140 registered trials. Frequency data was analyzed to determine the distribution of study designs. The majority of trials (70%) investigated the therapeutic effect of ketamine in mood disorders (unipolar: 60%, bipolar: 0.7%, both: 5.7%). Suicidal ideation (13.1%), post-traumatic stress disorder (5.4%), and obsessive-compulsive disorder (3.6%) were also investigated. Intravenous (IV) administration was the most common route with 87% of the studies using IV ketamine. Single-dose studies represented 50% of IV ketamine studies. Few studies were assessing maintenance treatment. Most studies were phase I or II with few definitive phase III trials registered. Given the large number of ongoing studies assessing psychiatric application of ketamine, researchers and relevant stakeholders should consider not only completed, published studies, but also ongoing registered studies in adjudicating the most relevant research questions. More definitive phase III trials and maintenance studies of IV ketamine for mood disorders are required, as numerous completed and ongoing studies have already assessed and demonstrated the proof-of-concept of acute antidepressant effects in phase I and II trials.
Competing Interests: Declaration of competing interest RSM declares that he has been on advisory boards and/or received honoraria for educational activities and/or research grants from AstraZeneca, Bristol-Myers Squibb, Janssen-Ortho, Eli Lily, Forest, Lundbeck, Pfizer, Shire, Merck, Sepracor, and Otsuka. JDR is a sub-investigator for the COMPASS Psilocybin for Treatment Resistant Depression Study. RSM is the director of and JDR is a staff psychiatrist at a clinic that administers intravenous ketamine. All other authors in this manuscript have reported no relevant conflict of interest.
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