Ketamine Shows Promise for Hard-to-Treat Depression in New Study

A brand new examine means that, for some sufferers, the anesthetic ketamine is a promising various to electroconvulsive remedy, or ECT, presently one of many quickest and best therapies for sufferers with difficult-to-treat despair. The examine is the most important head-to-head comparability of the 2 remedies.

Patients who don’t reply to a minimum of two antidepressants — about one-third of clinically depressed sufferers — have a situation that clinicians consult with as “treatment-resistant.” Their choices for reduction are restricted. Doctors usually advocate as much as 12 periods of ECT, which has a long-established efficacy, however is tainted by the stigma of historic misuse and horrifying Hollywood photographs of individuals strapped to tables, writhing in agony. Today’s ECT is way safer and performed beneath common anesthesia, however the process stays underutilized.

The examine, revealed on Wednesday in The New England Journal of Medicine, discovered that ketamine, when administered intravenously, was a minimum of as efficient as ECT in sufferers with treatment-resistant despair who do not need psychosis. (For folks with psychosis, ketamine, even in very low doses, can worsen psychosis-like signs.)

“The results were very surprising to us,” mentioned Dr. Amit Anand, lead creator of the examine and a professor of psychiatry at Harvard Medical School who research temper problems at Mass General Brigham. His workforce had initially hypothesized that ketamine can be almost as efficient as ECT. Instead, Dr. Anand mentioned, they discovered that ketamine carried out even higher than that.

This is important partly as a result of some sufferers are uncomfortable with ECT’s potential negative effects, corresponding to non permanent reminiscence loss, muscle ache or weak spot. (In uncommon instances it may end up in everlasting gaps in reminiscence.)

The examine, which was sponsored by the Cleveland Clinic Foundation, exhibits that ketamine is simpler to manage, with fewer changes throughout therapy and fewer sufferers dropping out, Dr. Anand mentioned. “More importantly, it shows that ECT, as expected, is associated with memory problems, while ketamine is not.” Intravenous ketamine additionally has negative effects, like dissociation, however that is “not usually an unpleasant experience for patients,” Dr. Anand mentioned.

Earlier research have proven that each remedies could be efficient in sufferers with hard-to-treat despair, however that analysis has primarily appeared on the two therapies independently. Dr. Roger S. McIntyre, a professor of psychiatry and pharmacology on the University of Toronto who just isn’t affiliated with the examine, known as it “groundbreaking.”

“It’s this type of rigorous, randomized, real-world pragmatic data that is robust and very clinically meaningful,” Dr. McIntyre mentioned.

The researchers randomly assigned intravenous ketamine or ECT to 365 sufferers. Nearly half obtained ketamine twice per week whereas the others obtained ECT thrice per week. By the top of the three-week therapy, 55 p.c of these within the ketamine group and 41 p.c of the sufferers within the ECT group reported a 50 p.c or higher discount in signs.

Six months later, the quality-of-life scores for each teams have been related.

One limitation of the examine was that the variety of ECT remedies might not have been enough as a result of the therapy interval was solely three weeks, mentioned Dr. Daniel F. Maixner, the ECT program director at Michigan Medicine on the University of Michigan, who was not affiliated with the examine.

The examine topics began their course of ECT by receiving electrical currents on one facet of the mind, which can require 10 or 12 periods, versus the 9 used within the examine, he added.

“If there’s more improvement to be had, you continue,” Dr. Maixner mentioned.

Patients who begin out bilaterally, stimulating each side on the identical time, typically want fewer periods. If the sufferers had accomplished extra ECT periods, then a higher proportion of them might have responded to the therapy, Dr. Anand mentioned, however that additionally would have probably precipitated extra negative effects.

A small variety of sufferers in each teams — beneath 33 p.c — went into remission, which means they’d solely gentle depressive signs. This means that further remedies can be wanted to ensure that the sufferers to keep up any reduction.

Continued therapy, nevertheless, comes with further dangers. With ketamine, for instance, longer therapy “increases the likelihood of both drug dependence and cognitive adverse effects, including dissociation, paranoia and other psychotic symptoms,” Dr. Robert Freedman, a professor of psychiatry on the University of Colorado, wrote in an editorial revealed with the examine.

Previous proof means that ECT remission charges could be a lot increased — typically a minimum of 60 p.c — however these research might have included a better proportion of inpatients in addition to sufferers with psychotic despair, for which ECT seems to be significantly efficient.

Researchers and clinicians are utilizing intravenous ketamine off label as a result of it has not been authorised by the Food and Drug Administration for therapy of temper problems, in contrast to its cousin esketamine, also referred to as Spravato, which is run nasally. Among clinicians, intravenous ketamine is extensively thought-about to be as efficient or extra so than esketamine for treatment-resistant despair, Dr. Anand mentioned.

Unfortunately, as a result of intravenous ketamine is a generic drugs, “it is unlikely that anyone is going to try to get F.D.A. approval for it to make it more reimbursable for insurers,” he added.

Later this 12 months, Dr. Anand and his colleagues will recruit sufferers for a bigger examine evaluating ECT to intravenous ketamine in 1,500 acutely suicidal and depressed sufferers, most of whom are more likely to be inpatients. They can even take a look at how the consequences differ by age teams, Dr. Anand mentioned.

Dr. Maixner, at Michigan Medicine, mentioned that analysis means that intravenous ketamine, which he has additionally used to deal with sufferers, might have some rising and powerful advantages for hard-to-treat despair, which “gives people options.”