A new study showed that when patients with severe, treatment-resistant bipolar depression were given a single intravenous (IV) dose of ketamine (also known as N-methyl-D-aspartate antagonist or NMDA), their symptoms improved within 40 minutes.
“In patients with treatment-resistant bipolar depression, robust and rapid antidepressant effects resulted from a single intravenous dose of an N-methyl-D-aspartate antagonist,” writes Carlos Zarate Jr., MD, of the National Institute of Mental Health in Bethesda, Md., and his colleagues.
Bipolar disorder, also known by its older name “manic depression,” is a mental disorder that is characterized by constantly changing moods. A person with bipolar disorder experiences alternating “highs” (what clinicians call “mania“) and “lows” (depression). Bipolar disorder affects about 2.6 percent of the U.S. population, according to the National Institute of Mental Health. Standard antidepressants may take weeks to months to become effective. Ketamine, which is sometimes used as a recreational drug, is legally used as an anesthetic. Zarate and his team have previously shown that ketamine can improve symptoms of unipolar depression; however, bipolar depression may respond differently to medication.
To determine whether an N-methyl-D-aspartate–receptor antagonist produces rapid antidepressant effects in subjects with bipolar depression, Zarate and his colleagues enrolled 18 patients with treatment-resistant bipolar depression in an randomized, double-blind, placebo-controlled trial. On average, these patients had failed to respond to a mean of seven previous antidepressant drugs, had been hospitalized for an average of nine weeks, and 55 percent had not responded to electroconvulsive therapy.
The study participants continued on therapeutic levels of lithium or valproate during the trial. Each received either an intravenous infusion of either ketamine or placebo on 2 test days 2 weeks apart. At the beginning of the study, at 40, 80, 110, and 230 minutes, and on days 1, 2, 3, 7, 10, and 14 after the infusion, the level of depression was measured using the Montgomery-Asberg Depression Rating Scale (MADRS).
Zarate and his team found that within 40 minutes, symptoms of depression were markedly improved in the patients who received ketamine, with an average decrease of 10 points in the MADRS score. By day 2, the symptoms had increased to an average decrease of more than 13 points in the MADRS, and there was a significant difference between the study subjects and those who received the placebo through day 3. The difference between the groups was gone by seven days.
Of those who received ketamine, 71 percent had improvement, and 6 percent responded to placebo.
One subject receiving ketamine and 1 receiving placebo developed manic symptoms, and the most common side effects of the ketamine were dissociative symptoms at the 40-minute point.
“To our knowledge, this is the first article detailing the rapid antidepressant effects of a single infusion of an NMDA [N-methyl-D-aspartate] antagonist in patients with treatment-resistant bipolar depression,” writes Zarate.
Zarate points out that their study was small and the patients had more severe depression of longstanding duration than most bipolar patients. “The toll of this protracted and refractory illness on the subjects was evident, in that two-thirds of participants were on psychiatric disability and nearly all were unemployed.”
The authors also state that it is unclear if the improvement seen with ketamine could be maintained, or how. Zarate and his colleagues are continuing their work with ketamine and depression.
Zarate’s paper can be seen in the August issue of the Archives of General Psychiatry
Source: Archives of General Psychiatry