Novel study reveals ‘fast-acting benefits’ of ketamine for depression

Written by Sharon Salt, Editor

In a study recently published in The American Journal of Psychiatry, a multi-institutional group of researchers have revealed that a nasal spray formulation of ketamine holds promise in the rapid treatment of symptoms of major depression and suicidal thoughts.
In the double-blind, multicenter, proof-of-concept Phase II study, the authors compared the efficacy of standard treatment plus intranasal esketamine or placebo for rapid reduction of symptoms of major depression among individuals at imminent suicide risk.

The study involved 68 participants randomly assigned to one of two groups – either receiving esketamine (84 mg) or placebo twice-weekly for 4 weeks. All participants continued to receive treatment with antidepressants throughout. The researchers examined the effects at 4 hours after first treatment, at 24 hours and at 25 days.

Their results revealed a significant improvement in depression scores and decreased suicidal ideation in the esketamine group compared to the placebo group at 4 hours and at 24 hours. The effects of esketamine were not greater than placebo at 25 days. According to the researchers, the measurement of suicide risk took into consideration both the patient’s and clinician’s perspective.

The researchers believe that the results of the study support the use of nasal spray esketamine as a possible effective rapid treatment for depressive symptoms in patients assessed to be at imminent risk for suicide. Additionally, they believe that esketamine could be an important treatment to bridge the gap that exists because of the delayed effect of most common antidepressants – that is, most antidepressants take 4–6 weeks to become fully effective.

The authors caution that more research is needed on the potential for abuse of ketamine and that it must go through a Phase III study before possible US FDA approval.

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In an accompanying editorial that was also published recently in The American Journal of Psychiatry, the editors of the journal discuss the need for additional research relating to the abuse potential of ketamine during Phase III trials, such as monitoring of patient’s craving and potential ketamine use from other sources.

While it is the responsibility of the physicians to provide a suicidal patient with the fullest range of effective interventions, the editors of the journal commented: “Protection of the public’s health is part of our responsibility as well, and as physicians, we are responsible for preventing new drug epidemics.”  They also suggested the need for broad input in the development of effective controls on the distribution and use of ketamine.

To conclude, the editors argue that steps to control the use of ketamine would not be aimed at preventing its use for beneficial purposes but would allow for treatments to “continue to be available to those with need, while the population that is at-risk for abuse is protected from an epidemic of misuse.”

Sources: Canuso CM, Singh JB, Fedgchin M et al. Efficacy and safety of intranasal esketamine for the rapid reduction of symptoms of depression and suicidality in patients at imminent risk for suicide: results of a double-blind, randomized, placebo-controlled study. Am. J. Psych. doi:10.1176/appi.ajp.2018.17060720 (2018) (Epub ahead of print);