First Drug Shown Effective For Treating Chronic Forms Of Major Depression

November 18, 1998

A dose of sertraline a day keeps the deepest depression away. A new study shows that the drug, prescribed under the brand name Zoloft, can safely stop depression from recurring even in the most chronic sufferers.

The findings are the first to suggest an effective drug treatment for patients with the severest and most disabling forms of chronic depression. For these individuals, the study reports that sertraline protects against recurrence and greatly extends remission time. The drug is currently not indicated for use in the treatment of chronic depression. Previous research has shown sertraline to be effective in preventing relapse in patients suffering non-chronic episodes of major depression.

About three percent of the population suffers from chronic forms of depression, marked by disabling psychological and social problems. These individuals are often misdiagnosed as having character or personality disorders. In the study, many patients had suffered chronic major depression - a severe form of at least two years duration - for more than 20 years. Other patients suffered double depression - an acute form of major depression - combined with dysthymia, a chronic, milder depression present for at least two years.

The 19-month study appears in the current issue of the Journal of the American Medical Association. The research involved 161 patients treated at outpatient psychiatric clinics at 10 academic medical and two clinical research centers. Before entering the study, the patients had responded positively to sertraline in a 12-week trial and had continued to respond well in a four-month extended treatment. In the study, 77 patients maintained sertraline use for 76 more weeks, while 84 patients took a placebo daily.

A research team found that patients receiving sertraline were 4.1 times less likely to suffer depression recurrence than those taking a placebo. The researchers called sertraline "very well tolerated" over many months at an average daily dose of about 146 mg. Indeed, just one side effect was found to be statistically significant. Thirteen sertraline patients complained of sexual dysfunction compared to two individuals on placebo, a side effect commonly seen with antidepressant treatments. The study was funded by Pfizer Inc.

"The bottom line is that chronic types of depression are disabling and vastly undertreated," said Martin B. Keller, M.D., who directs the research. "The study describes an effective way to deal with chronicities if identified and consistently treated." Keller is professor and chairman of the Department of Psychiatry and Human Behavior in the Brown University School of Medicine.

The findings complement those in three new articles, of which Keller is the lead or co-author, reporting on the initial 12 weeks of chronic-depression treatment. To be published in the November issue of the Journal of Clinical Psychiatry, the articles describe rapid improvement in the psychological and social behaviors among 635 depressed patients treated with either sertraline or the drug imipramine. From increased productivity at work to better social relationships, patients showed great improvements, Keller said.

However, almost one-third of people with chronic forms of depression do not fill their first prescription, and most discontinue treatment prematurely, he said. "If you respond positively to sertraline but discontinue treatment, you have an extremely high likelihood of relapse and developing full blown episodes of depression. Improvements in work productivity and psychosocial behavior are lost. It is important to stay on treatments."

The research does not suggest that depressed patients be treated only with drugs, Keller said. The most effective treatments may combine medication and psychotherapy, he said. Keller is currently leading a large-scale study of medication alone, psychotherapy alone, and the combination of both in patients with chronic depression.

Zoloft is one of four medications in use, including Prozac, Paxil and Celexa, that belong to the class of drugs called SSRI's, selective seretonin re-uptake inhibitors. The drugs block re-uptake of the chemical seretonin in the synapses between neurons in the nervous system. This action is thought to alleviate the symptoms and syndromes of depression, and keeps them from returning.
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Brown University

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