A small sample of patients with bipolar disorder displayed noteworthy improvement in their depressive symptoms after being treated with the rapid-acting antidepressant intravenous ketamine and the nasal spray esketamine, according to a new Yale led-study.
The study, published October 2 in the Journal of Clinical Psychiatry, also found that patients were not at higher risk of suffering a manic episode during the acute phase of treatment.
Ketamine is approved for use in anesthesia, and Yale researchers were the first to discover in the 1990s that it could also provide rapid relief to chronically depressed patients.
The U.S. Food and Drug Administration in 2019 approved intranasal esketamine to treat depression in adults. However, little data is available on the use of ketamine or esketamine to treat bipolar disorder, a serious illness that leads to reduced quality of life for sufferers.
A Yale research team reviewed records of patients with treatment refractory bipolar depression who were referred to Yale Psychiatric Hospital Interventional Services for treatment from October 2014 to November 2023.
Forty-five patients were treated twice weekly for up to four weeks with intravenous ketamine or esketamine. Overall, 39 percent achieved a clinical response to treatment and 13 percent achieved remission. No patients experienced mania or hypomania during the acute series phase, where treatments were administered twice per week.
Results showed there were 16 manic or hypomanic events over a total follow-up period of 518 patient-months. Only one event was severe and required hospitalization. The median time from first treatment to manic/hypomanic event was 266 days, which is much greater than the median overall length of treatment (95 days), suggesting that ketamine or esketamine did not greatly increase the risk of manic/hypomanic events.
“Patients with bipolar depression often don’t have a lot of options,” said Samuel T. Wilkinson, MD, associate professor of psychiatry and senior author. “Our study is the largest to date reporting safety outcomes on a sample of real-world patients with bipolar depression treated with ketamine or esketamine. It’s not the definitive study, but it does help clinicians better understand the potential risks and benefits.”
Mia C. Santucci, BA, postgraduate associate at Yale School of Medicine, was the lead author.
Other Yale contributors were Mina Ansari, MD, MPH; Sina Nikayin, MD; Rajiv Radhakrishnan, MBBS, MD; and Taeho G. Rhee, PhD.