The results of two new studies may signal a substantial shift in the way psychiatrists and researchers think about treatment for severely depressed patients.
In one, government researchers found that an injection of a powerful anesthetic drug dissolved feelings of despair in a small group of severely depressed patients in a matter of hours, and that the effect lasted for up to a week in some participants.
Doctors cautioned that the study was very small, and that the drug, ketamine, is a tightly controlled substance sometimes used as a club drug that can cause hallucinations, confusion and dangerous reactions, especially when ingested in unknown doses.
In the other, psychiatrists in New York found evidence that antidepressant drugs significantly increased the risk that some children and adolescents would attempt or commit suicide. Doctors have debated this risk for years, but the authors of the study were skeptical of it, and their report may sway others.
Both studies are being published in The Archives of General Psychiatry.
In the first study, Dr. Carlos A. Zarate of the National Institute of Mental Health led a team of researchers who treated 18 chronically depressed men and women with the anesthetic ketamine.
Five participants recovered from depression in the first day and were still significantly improved a week later. Most patients also received a placebo treatment during the study, an injection of saline solution, and showed no improvement.
Dr. Zarate said experimenting with novel approaches was crucial because the current crop of antidepressant drugs worked slowly and weakly, if at all, for millions of patients.
Ketamine affects the brain in a way entirely different from drugs like Prozac, and it has shown some antidepressant effects in animal studies. It had not been tried for depression in humans.
“What the study tells us is that we can break this sound barrier, in effect, and get an almost immediate response that we cannot get with other drugs,” Dr. Zarate said.
Ketamine is not approved for depression, and it has a checkered past in psychiatric research. The drug often induces hallucinations, like whispering voices and light trails, and researchers used it in the 1990’s to induce psychotic reactions in people with schizophrenia — an experiment widely criticized as unethical.
Dr. Zarate said that neither doctors nor patients should use it for depression outside of carefully controlled research settings and that the results of the current trial should be considered suggestive. “This drug should be seen as a tool for understanding what mechanisms might be involved in rapid relief,” and not as a treatment, Dr. Zarate said.
The study of suicide risk, led by Dr. Mark Olfson of Columbia University and the New York State Psychiatric Institute, was based on an analysis of Medicaid records of more than 4,400 people who were hospitalized for depression in 1999 and 2000.
The researchers found no link between the antidepressant drugs and suicidal behavior in depressed patients 19 or older. But children and adolescents in the study who were taking antidepressants were about 50 percent more likely than those not on the drugs to try to kill themselves. And they were about 15 times as likely as those not on the medications to complete the act, although the number of suicides was too small to draw definitive conclusions, the authors cautioned.
In addition, there could be differences between the two groups that the Medicaid records didn’t reveal: the children who received the drugs may have been more severely ill, skewing the results, they said.
In 2004, the Food and Drug Administration required strong warnings on the labels of antidepressant drugs alerting parents and doctors of a possible suicide risk in some children. Since then many psychiatrists have been skeptical of the suicide link.
“I was surprised by what we found,” Dr. Olfson said. “I set out thinking we’d find that the drugs” significantly reduced suicide risk.
The findings may prompt researchers to look at which children are most at risk, rather than continuing to debate whether the risk exists, he said.