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

According to a new study, ketamine, an anesthetic, may be a promising treatment for certain patients. ECT is currently the fastest and most effective therapy for depression patients who are difficult to treat. This is the largest comparison of both treatments.

They have limited options for treatment. Doctors recommend up to twelve sessions of ECT. It is effective and has been used for many years, but it's stigmatized by historical abuse and the frightening Hollywood images that show people strapped on tables, writhing with pain. The ECT of today is safer, and it's done under general anesthesia. However, the procedure is still underused.

The study published in The New England Journal of Medicine on Wednesday found that ketamine administered intravenously was as effective as ECT for patients with treatment resistant depression without psychosis. Even in low doses, ketamine can worsen psychotic symptoms for people with psychosis.

The results of this study were very unexpected, said Dr. Amit A. Anand, the lead author and professor of psychiatry, Harvard Medical School, who studies mood disorders in Mass General Brigham. His team initially hypothesized ketamine to be almost as effective as ECT. Dr. Anand stated that they were surprised to find that ketamine was even more effective than ECT.

It is important because some patients may be uncomfortable with ECT side effects such as temporary muscle pain, weakness or memory loss. In rare cases, it can cause permanent memory gaps.

Dr. Anand stated that the study sponsored by Cleveland Clinic Foundation shows that ketamine can be administered more easily, with less adjustments being made during treatment, and fewer patients quitting, compared to other drugs. 'More important, it shows that ECT is, as expected with memory problems while ketamine does not.' Intravenous intraketamine can also cause side effects like dissociation. However, Dr. Anand says that this is not a common experience.

Both treatments have been shown to be effective for patients with difficult-to-treat depressive disorders, but the research focused on each therapy separately. The study was described as 'groundbreaking' by Dr. Roger S. McIntyre of the University of Toronto's Department of Psychiatry and Pharmacology, who is not associated with the research.

Dr. McIntyre stated that 'this type of rigorous randomized data from real-world situations is robust and clinically significant'.

Researchers randomly assigned intravenous ketamine to 365 patients. Nearly half of the patients received ketamine two times a weeks, while the other half received ECT three time a week. At the end of a three-week period, 55 percent in the ketamine treatment group and 41 % in the ECT treatment group reported a 50% or greater reduction of symptoms.

Six months after the first group, both scores were similar.

The study had a limitation in that it may have not been enough ECT treatments because the treatment period only lasted three weeks. Dr. Daniel F. Maixner is the ECT Program Director at Michigan Medicine, University of Michigan. He was not involved with the study.

He added that the subjects in the study began their ECT course by receiving currents on only one side of the head. This may have required 10 or 12 sessions instead of the nine they used in the study.

Dr. Maixner stated, 'If you think there is more improvement that can be made, then continue'.

Patients who begin bilaterally and stimulate both sides simultaneously often require fewer sessions. Dr. Anand stated that if the patients had received more ECT treatments, a higher proportion would likely have responded. However, this could have also caused more side-effects.

In both groups, a small percentage of patients -- less than 33 percent -- experienced remission. This means they only had mild symptoms of depression. It is clear that the patients would need additional treatment to continue feeling better.

Continuing treatment comes with added risks. In the case of ketamine treatment, Dr. Robert Freedman of the University of Colorado's Department of Psychiatry wrote that longer treatment increases the risk of drug dependence as well as cognitive adverse effects such dissociation and paranoia.

Previous studies suggest that ECT remission can be higher -- at least 60% -- but they may have included a greater percentage of patients who were inpatients, as well as those with psychotic depression for whom ECT seems to be especially effective.

Researchers and clinicians use intravenous ketamine without a prescription because the Food and Drug Administration has not approved it for mood disorders. This is in contrast to its nasal cousin esketamine (also known as Spravato), which has been approved. Dr. Anand stated that intravenous Ketamine is considered by many clinicians to be just as effective, if not more, than esketamine in treating treatment-resistant depression.

It is not likely that anyone will try to get F.D.A. approval for intravenous Ketamine to make it more reimbursable by insurers. It is unlikely that anyone will try to get F.D.A. approval for it, he said.

Dr. Anand will be recruiting patients later this year for a large study comparing intravenous ketamine to ECT in 1,500 acutely depressed and suicidal patients. The majority of these patients are likely to have been inpatients. Dr. Anand added that they will also examine how the effects vary by age group.

Dr. Maixner at Michigan Medicine said that research indicates that intravenous Ketamine, that he also uses to treat his patients, could have some emerging and powerful benefits for depression that is hard to treat, giving people 'options'.