Ketamine promising in treating major depression and suicidal thoughts

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Structural model of Ketamine on the blackboard.Ketamine has “shown promise” in the rapid treatment of major depression and suicidal thoughts, BBC News reports. Ketamine has a reputation as a party drug but is licensed as an anaesthetic. The American study found use of the drug via a nasal spray led to “significant” improvements in depressive symptoms in the first 24 hours.

The Royal College of Psychiatrists said it was a “significant” study that brought the drug “a step closer to being prescribed on the NHS”.

The report says the study by researchers from Janssen Research and Development, a Johnson and Johnson company, and Yale School of Medicine, is the first study into ketamine as a treatment for depression that has been done by a drug company.

The trial looked at 68 people at imminent risk of suicide. All patients were treated with a stay in hospital and anti-depressants. In addition, half were given ketamine in the form of esketamine (part of the ketamine molecule) in a nasal spray and half were given a placebo.

The report says the study found those using esketamine had a much greater improvement in depression symptoms at all points over the first four weeks of treatment. However, at 25 days the effects had levelled out.

The study’s authors suggest it could offer an effective rapid treatment for people severely depressed and at imminent risk of suicide and could help in the initial stages of treatment, as most anti-depressants take four to six weeks to become fully effective.

The nasal spray is now undergoing phase three trials before it can be licensed for treatment.

The report says there were no reports of esketamine dependence or misuse in the trial but the authors warn that more research is needed on the potential for abuse of ketamine and say these should be looked at during subsequent trials.

Scientists in the UK are also studying ketamine as a treatment for depression taken intravenously. Dr James Stone, from the Royal College of Psychiatrists, is quoted in the report as saying the “interesting” US study confirmed the findings from successful studies into intravenous ketamine.

“The main reason for its significance is because this is being developed by a drug company and its potentially quite likely that this medication might become available as a treatment available on the NHS for depression.” He said because it was being given as a nasal spray it was “much easier to administer” than intravenous ketamine and was “potentially quicker to give, so it means more people can be dosed at the same time” and you need less equipment.

Stone said if it did go on to be prescribed on the NHS it would be aimed at people with severe depression as a second or third line of treatment if other drugs haven’t worked and could be used for people instead of electroconvulsive therapy.

Professor Mitul Mehta from King’s College London said in the report that it was an “exciting” study. “All the studies to date have been looking at intravenous use – there are some people who have explored oral ketamine but that doesn’t appear to be as successful as intravenous so intranasal seems to be a really good halfway-house. It enters the body relatively quickly – it’s not as fast as going straight into your bloodstream but not as slow as via the stomach and it’s reasonably easy to control how much you give to a person. In that respect this is a really important study.”

But he said far bigger studies are needed to look out for any rare side-effects.

Because ketamine is licensed to be used by doctors as an anaesthetic it can be prescribed off licence for depression. This is happening in private clinics in the US and the UK. But, the report says, to be prescribed on the NHS, it would need to be licensed to be used as a treatment for depression.

In the UK, doctors have been trialling ketamine to treat depression since 2011. Dr Rupert McShane, who has led a trial in Oxford, says ketamine can work on patients with depression “where nothing has helped before”.

According to the report, he has called for a national registry to monitor its use.

Abstract
Objective: The authors compared the efficacy of standard-of-care treatment plus intranasal esketamine or placebo for rapid reduction of symptoms of major depression, including suicidality, among individuals at imminent suicide risk.
Method: In a double-blind, multicenter, proof-of-concept study, 68 participants were randomly assigned to receive esketamine (84 mg) or placebo twice weekly for 4 weeks, in addition to comprehensive standard-of-care treatment. The primary efficacy endpoint was change in score from baseline to 4 hours after initial dose on the Montgomery-Åsberg Depression Rating Scale (MADRS). Clinician global judgment of suicide risk (from the Suicide Ideation and Behavior Assessment Tool) was also assessed. Secondary endpoints included these measures at 24 hours and double-blind endpoint at day 25.
Results: A significantly greater improvement in MADRS score was observed in the esketamine group compared with the placebo group at 4 hours (least-square mean difference=−5.3, SE=2.10; effect size=0.61) and at ∼24 hours (least-square mean difference=−7.2, SE=2.85; effect size=0.65), but not at day 25 (least-square mean difference=−4.5, SE=3.14; effect size=0.35). Significantly greater improvement was also observed in the esketamine group on the MADRS suicidal thoughts item score at 4 hours (effect size=0.67), but not at 24 hours (effect size=0.35) or at day 25 (effect size=0.29). Between-group reductions in clinician global judgment of suicide risk scores were not statistically different at any time point. The most common adverse events among participants in the esketamine group were nausea, dizziness, dissociation, unpleasant taste, and headache.
Conclusions: These preliminary findings indicate that intranasal esketamine compared with placebo, given in addition to comprehensive standard-of-care treatment, may result in significantly rapid improvement in depressive symptoms, including some measures of suicidal ideation, among depressed patients at imminent risk for suicide.

Authors
Carla M Canuso, Jaskaran B Singh, Maggie Fedgchin, Larry Alphs, Rosanne Lane, Pilar Lim, Christine Pinter, David Hough, Gerard Sanacora, Husseini Manji, Wayne C Drevets

BBC News report
American Journal of Psychiatry abstract


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