Ketamine Spurs Improvement in Depression
The anesthetic ketamine can reduce symptoms in patients with treatment-resistant depression within several hours of infusion, according to a study funded by the National Institute of Mental Health and published in the Archives of General Psychiatry, the Boston Globe reports (Goldberg, Boston Globe, 8/8).
For the study, Carlos Zarate, chief of the Mood Disorders and Anxiety Unit at NIMH, and colleagues administered ketamine infusions to 18 men and women with chronic depression (Carey, New York Times, 8/8). The participants had tried an average of six different antidepressants without success (Boston Globe, 8/8).
Two hours after receiving the infusion, half of the participants experienced a 50% reduction in depression symptoms, according to the study. Seventy-one percent of participants experienced a similar decrease in symptoms one day after receiving the infusion, and more than one-third continued to experience the improvement after seven days, the study finds.
Nearly one-third of participants reported that their symptoms ended completely (Vedantam, Washington Post, 8/8). It typically takes at least eight weeks for individuals with treatment-resistant depression to first experience an improvement in symptoms with use of conventional antidepressants, while individuals who respond well to such treatments might experience an improvement in four to six weeks, Scripps Howard/Detroit News reports (Bowman, Scripps Howard/Detroit News, 8/8).
Some participants experienced known side effects of ketamine, including an initial period of dissociation during which they felt disconnected or had difficulty expressing their thoughts through words (Washington Post, 8/8). Ketamine, which is not approved for treatment of depression, sometimes is used illicitly as a "club drug" and can produce hallucinations, confusion and dangerous reactions, the Times reports (New York Times, 8/8).
The "unanswered questions" raised by the study include "whether patients will be able to tolerate the drug for long period, and whether it will continue to be effective" over time, the Post reports.
Researchers said much more research must be conducted before the findings could produce a direct benefit for patients. Researchers said they hope the findings will encourage pharmaceutical companies to develop compounds that act similarly to ketamine but that produce fewer side effects and can be tested on a larger scale.
Zarate said, "Psychiatrists have gotten used to the idea we have to wait weeks or months" for depression treatments to take effect, "but we can break the sound barrier and get an antidepressant effect within hours" with ketamine infusions. Ketamine, which targets a neurotransmitter called glutamate, "is almost like rebooting a computer," Zarate said, adding, "It is a chemical reboot, and the striking thing is the effect lasts for about a week" (Washington Post, 8/8).
Zarate cautioned that ketamine should not be used by physicians or patients outside of research settings. "This drug should be seen as a tool for understanding what mechanisms might be involved in rapid relief," he said (New York Times, 8/8).
Thomas Insel, director of NIMH, in a statement said, "To my knowledge, this is the first report of any medication or other treatment that results in such pronounced, rapid, prolonged response with a single dose."
NIH Director Elias Zerhouni said in a statement, "The public health implications of being able to treat major depression this quickly would be enormous" (Boston Globe, 8/8).
A separate study, also published in the Archives of General Psychiatry, finds that children ages six to 18 who attempt or commit suicide are 1.5 times more likely to have been using antidepressants than peers who do not attempt or commit suicide, Long Island Newsday reports (Talan, Long Island Newsday, 8/8).
Lead author Mark Olfson of Columbia University and the New York State Psychiatric Institute and colleagues analyzed Medicaid records of more than 4,400 children, adolescents and adults who were hospitalized for depression in 1999 and 2000. The study finds no link between antidepressant use and suicide risk in adults.
The study also finds that children and adolescents who used antidepressants were about 15 times more likely to actually commit suicide than were patients of the same age who did not use antidepressants, although the number of suicides was too small to be statistically significant. In addition, the researchers said it is possible that there are differences between the two groups that were not revealed by the Medicaid records.
For example, young people who received antidepressants could have been more severely depressed than those who did not, researchers said.
Olfson said, "I was surprised by what we found," adding, "I set out thinking we'd find that the drugs" would reduce the chance of suicide (Wall Street Journal, 8/8).
Gabrielle Carlson, director of child and adolescent psychiatry at Stony Brook School of Medicine, said, "This is not a big effect," adding that parents should "talk to their child's doctor and weigh the benefits of taking these medicines and the risks" (Long Island Newsday, 8/8).