NEW DEPRESSION FINDINGS COULD ALTER TREATMENTS

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.