U.S. PSYCH: Depression Remission Rates Remain Low, But There's Hope

SAN FRANCISCO, April 25 -- Remission rates remain low for major depression even with multiple antidepressant drug classes available, but the recently approved selegiline patch (Emsam) aims to bring the rates up.

"The mission for the condition is remission," said James W. Jefferson, M.D., of the University of Wisconsin in Madison, but "we are still stuck with this low remission rate."

Just getting a response with treatment, defined as reducing depression scores by at least half, is not enough, he said in a presentation here at the U.S. Psychiatric and Mental Health Congress regional extension.

The consequences of failing to achieve remission include greater relapse risk, increased risk of resistance to treatment, and worse prognosis for Axis III disorders.

Remission should encompass complete resolution of symptoms and full restoration of psychosocial and work-related functioning, Dr. Jefferson said. But the cutoffs that somewhat arbitrarily define remission on rating scales -- such as a score of seven or more on the Hamilton Rating Scale for Depression -- allow for residual symptoms.

Several studies, including the National Institutes of Health-funded STAR*D trial (Sequenced Treatment Alternatives to Relieve Depression), have shown complete remission rates as low as 7%, he noted.

While there are few neuropeptide-based agents on the horizon for depression, a new administration route of an old agent may be a new tool in improving remission rates, Dr. Jefferson suggests.

The monoamine oxidase inhibitors were "decent drugs but a little hard to use," he acknowledged. Adverse events, particularly the risk of acute hypertensive effects with tyramine intake from cheese and other foods and with concomitant use of over-the-counter decongestants, were a major problem.

But the selegiline transdermal patch, FDA approved in February 2006 for treating depression, bypasses the gut to eliminate those problems, Dr. Jefferson said.

One study showed a "large margin of safety" for tyrosine intake and others showed it was well-tolerated compared with placebo, which led the FDA to allow the lowest dose of the drug (6 mg/day) to be used without dietary restriction.

Five placebo-controlled clinical trials have now been done, of which two were positive for efficacy, two showed a trend toward efficacy, and one failed. The one placebo-controlled study of the selegiline patch showed it was effective in preventing relapse.

"Monoamine reuptake is helpful for half of depressed patients, but only a third or fewer reach remission," Dr. Jefferson concluded. "Other mechanisms of action are needed and are becoming available."

In a study of fluoxetine (Prozac) published in the Journal of Clinical Psychiatry in 1999, only 20% of patients who achieved a remission score were fully in remission. Of the rest, 44% had sleep disturbance, 38% had fatigue, and 27% had low interest or pleasure scores.

For a more clinically relevant look at remission rates, the NIH-funded STAR*D trial (Sequenced Treatment Alternatives to Relieve Depression) was undertaken. The results were published in 2006 in the American Journal of Psychiatry and the New England Journal of Medicine.

In the trial, patients progressed from initial treatment with citalopram (Celexa) to bupropion (Wellbutrin), sertraline (Zoloft), venlafaxine (Effexor), or augmented citalopram, then to mirtazapine (Remeron) or nortriptyline (Aventyl, Pamelor) or their previous therapy augmented with lithium or another antidepressant, and finally to tranylcypromine (Parnate) or mirtazapine plus venlafaxine.

Only about 30% of patients achieved remission in the first treatment level. In the second level, remission was about 20% when medication was switched or about 30% when it was augmented, with no significant difference between medications.

In the third level, remission was 12% to 19% when medication was switched and 16% to 25% when it was augmented, with no difference between the medications in remission rates.

By the fourth level, remission rates were "terribly low" at 7% and 14% with no significant difference between treatments.

STAR*D showed how hard it is to achieve remission, Dr. Jefferson said.

Nonetheless, "don't settle for less than remission," he admonished psychiatrists. "Don't give up!"