Columbia University Medical Center

Follow-Up Therapy Extends Depression Treatment Benefits

New York, NY, March 16, 2001—A well-established treatment for severe and often medication-resistant depression, electroconvulsive therapy, gives much more lasting benefits when followed up with a combination drug therapy, a study led by a Columbia researcher suggests.
The study was published in the March 14 issue of the Journal of the American Medical Association. Electroconvulsive therapy (ECT), in which an electric current is passed through the brain, is recognized as safe and effective in treating the severely depressed, especially those who are psychotic, suicidal, who refuse to eat, or who have not benefited from medication. The number of ECT procedures in the United States exceeds coronary bypass, appendectomy, or hernia repair.
In the mid-1900s, indiscriminate use of ECT gave it a dark reputation, exemplified in the 1975 film, “One Flew Over the Cuckoo’s Nest.” ECT use today is carefully controlled, and experts advocate lifting the shroud of stigma and fear around the procedure. An editorial in the same issue of the journal discusses this issue.
One drawback of ECT treatment, however, is that many patients relapse into the depressive symptoms within six months. In the 1960s, drugs were identified that could prevent this in many patients, but the relevance of those drugs to the types of patients who presently receive ECT is questionable.
Studies in the 1990s, largely conducted at Columbia, found that relapse was much more of a problem than the field had really appreciated, said Harold A. Sackeim, Ph.D., a professor of clinical psychology in psychiatry and radiology at Columbia.
Dr. Sackeim, who is also chief of biological psychiatry at the New York State Psychiatric Institute, led the new study. It found that a combination drug follow-up treatment leads to a markedly lower relapse rate.
The new treatment consists of lithium — a drug often used to help prevent or reduce mood swings — and nortriptyline, one of an important class of drugs called tricyclic antidepressants. Tricyclic antidepressants alone have been commonly used to help prevent relapse, but the new study suggests the combination therapy works better. The study compared patients who took the combination treatment, nortriptyline alone, and a placebo.
Nortriptyline-lithium combination therapy had a marked advantage in time to relapse, superior to both placebo and nortriptyline alone, the authors wrote. Over the 24-week trial, the relapse rate for placebo was 84 percent; for nortriptyline, 60 percent; and for nortriptyline-lithium, 39 percent.
Investigators at Columbia designed and monitored the project. It was conducted from 1993 to 1998 at the Carrier Foundation, Belle Meade, N.J., and at two university-based psychiatric facilities at the University of Iowa, Iowa City, and Western Psychiatric Institute and Clinic, Pittsburgh.
The idea for nortriptyline-lithium therapy came from the fact that it has been successfully used to treat acute depression resistant to other treatments, Dr. Sackeim said. The authors say two other strategies should be tested to further improve relapse rates. These approaches are meant to provide more therapeutic protection to patients during a crucial five-to-six week period, typically right after ECT therapy, when they are most vulnerable to relapse.
One strategy is to taper ECT over a few weeks, as is commonly done with pharmacological treatments, providing symptom suppression during the most vulnerable period. Second, the antidepressant medication used in continuation therapy may be started during the course of ECT, followed by post-ECT addition of lithium, they write. The National Institute of Mental Health has funded a large trial to test these strategies, Dr. Sackeim said.
In an editorial in the same issue of the JAMA, Deputy Editor Richard M. Glass, M.D., discusses the new research in the context of ECT’s history and the need to give the procedure more public acceptance. For the sake of the many patients with major depression and their families, it is time to bring ECT out of the shadows, he concludes.
The results of ECT in treating severe depression are among the most positive treatment effects in all of medicine, Dr. Glass also writes. ECT has had response rates reported in the range of 80 percent to 90 percent as a first-line treatment, and in the range of 50 percent to 60 percent for patients who have not responded to one or more trials of treatment with antidepressant drugs.
The new study on combination follow-up therapy was supported by the National Institute of Mental Health, Solvay Pharmaceuticals Inc. (which donated the lithium), and MECTA Corp. (which provided the ECT devices.)

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