Ketamine’s controversial role in treating depression has been boosted by a new randomised controlled trial showing it significantly and rapidly reduces suicidal ideation.Among a group of 80 severely depressed individuals already on pharmacotherapy, the US researchers found that a single, subanaesthetic infusion of ketamine was associated with a greater reduction in clinically significant suicidal ideation within 24 hours than a control midazolam infusion.After one day, 55% of the patients who received the ketamine infusion had more than halved the severity of their suicidal ideation, compared with 30% in the midazolam group.What’s more, and in contrast to previous studies on ketamine infusions, the improvement appeared to persist for at least six weeks combined with optimised pharmacotherapy, the study authors wrote in the American Journal of Psychiatry.Ketamine was first mooted as having antidepressant properties back in the 1990s, after having first been approved by the US FDA for anaesthetic use in 1970.There had been reports that it could reduce suicidal ideation, but to date the evidence to support this has been lacking.In this study, researchers used the validated Scale for Suicidal Ideation to monitor the participants who were all psychiatric outpatients. The scale categorises a score of over two as predictive of suicide in the next 20 years. The depressed adults enrolled in this study were rated as having a score of at least four– ‘a clinically significant cut-off for suicidal ideation.’Midazolam was chosen as the comparator in the trial because, like ketamine it is a psychoactive anaesthetic agent with a similar half-life but no established antidepressant or antisuicidal effects.The finding that only four patients needed to be treated with ketamine to see a benefit over midazolam was described as a ‘medium effect’, but nonetheless significant given the lack of evidence-based pharmacotherapy currently available for suicidal patients with major depressive disorders.“Suicidal depressed patients need rapid relief of suicidal ideation,” the study authors said. And yet, despite suicidal behaviour often being associated with depression, most antidepressant trials have excluded suicidal patients and did not assess suicidal ideation and behaviour.“Standard antidepressants may reduce suicidal ideation and behaviour in depressed adults …. but this effect takes weeks,” they said.Consequently, for many, the findings of this study represent a promising new option for an area of medicine that has been notoriously difficult to treat.An accompanying editorial, also acknowledges the hope this study represents.“[T]he excitement about ketamine in our field is a reflection of the serious challenges we face in managing treatment-resistant depression,” said Dr Charles Nemeroff, leading US psychiatrist in his editorial.But he says significant concerns still exist with regard the inclusion of ketamine in the psychiatrist’s toolkit.Who regulates the use of ketamine? How do we handle its potential as a drug of abuse? Exactly how does it work?These are just some of the questions that need to be answered before it can be seriously considered as part of mainstream psychiatric medicine, Dr Nemeroff suggests.In addition, he says we may looking for a new, quick fix solution for patients too early – before having really tried all other possible treatments.“When treated with monoamine oxidase inhibitors, tricyclic antidepressants, ECT, repetitive transcranial magnetic stimulation, or augmentation with lithium, T3, atypical antipsychotics, or pramipexole, many patients with treatment-resistant depression show remarkable improvement,” he said.He suggests a ‘wait and see’ attitude be adopted, as the research and study results come in, and the evidence to support ketamine’s exact role in the world of mental illness becomes clearer.Ref: Am J Psychiatry 2018; 175: 327-335; doi:10.1176/appi.ajp.2017.17060647 Am J Psychiatry 2018; 175: 297-299; doi:10.1176/appi.ajp.2018.18010014
Expert/s: Dr Linda Calabresi








