YOKOHAMA, JAPAN -- A new wave of depression treatment options will soon reach U.S. psychiatrists.
The recent approval of escitalopram to treat major depression is likely to be followed shortly by approvals of two other novel antidepressants--the neurokinin-1 receptor antagonist MK-869 and the dual reuptake inhibitor duloxetine, Dr. Charles B. Nemeroff said at the 12th World Congress of Psychiatry.
Several other experimental therapies for depression also are in trials, said Dr. Nemeroff, professor and chairman of psychiatry at Emory University, Atlanta.
He and Dr. David J. Kupfer, professor and chair of psychiatry at the University of Pittsburgh, gave a rundown on developments in the field for clinicians at the congress, sponsored by the World Psychiatric Association. Dr. Nemeroff is a paid consultant for all the pharmaceutical companies that make antidepressants. Dr. Kupfer is a paid consultant for Forest Laboratories, which makes escitalopram, and for Eli Lilly & Co., which makes duloxetine. The session was funded by an unrestricted grant from Forest Laboratories.
New treatment options will include:
* Escitalopram (Lexapro). Unquestionably the most selective of the selective serotonin reuptake inhibitors (SSRIs), the single-isomer drug escitalopram (or S-citalopram) is about twice as potent as its cousin citalopram in blocking 5-HT reuptake and has virtually no effect on any other transporter or receptor, making it less likely to cause side effects or drug-drug interactions, Dr. Nemeroff said.
It recently gained U.S. Food and Drug Administration approval to treat major depressive disorder at a dosage of 10 mg/day, which is from one-half to one-quarter the recommended daily dosage of citalopram.
Among the five studies that led to escitalopram's approval, a pooled analysis of three randomized, double-blind, placebo-controlled trials involving 1,321 patients with major depression showed that both escitalopram and citalopram were more effective than placebo, with escitalopram showing efficacy in the first week of treatment and citalopram's effects starting around week 6, Dr. Kupfer said.
Close to 40% of patients on either drug achieved remission of depression, compared with approximately 30% of patients on placebo.
In a separate study of patients who responded to escitalopram for depression, 26% of patients randomized to 8 months of maintenance therapy with the drug relapsed into depression, compared with 40% on maintenance with placebo.
A recent study in rats found that, unlike escitalopram and citalopram, injections of the R-isomer of citalopram (R-citalopram) did not block serotonin reuptake at all, raising the question of whether the Risomer blocks some of the effects of the S-isomer m the racemic mixture or citalopram, leaving citalopram less potent than escitalopram.
"If that's the case, that is a very very novel finding," Dr. Nemeroff said. "This would be a precedent in neuropharmacology."
* Duloxetine. Approval is pending and "extremely likely" both in the United States and in other countries for duloxetine, a drug made by 1311 Lilly that inhibits both serotonin and norepinephrine reuptake, he said.
In six placebo-controlled clinical trials for the treatment of depression using 60120 mg/day duloxetine, results showed definitive efficacy in three studies and were suggestive of efficacy in two more.
In one 9-week study of 245 patients, for example, Hamilton Depression Scale scores improved significantly in patients on duloxetine by week 2 and through the end of the 9-week trial, compared with placebo (J. Clin. Psychiatry 63:308-15, 2002).
When the more rigorous criterion of remission was used, investigators found that 44% of patients on duloxetine were no longer depressed, compared with 16% on placebo-numbers that Dr. Kupfer called "reassuring."