May 23, 2002

IS MAJOR CHANGE NEEDED AT THE FOOD AND DRUG ADMINISTRATION?

By Nathaniel S. Lehrman, MD

Dr. Lehrman, now retired, was Clinical Director, Kingsboro Psychiatric Center, Brooklyn NY

Is drastic change necessary in the approach, and perhaps the leadership, of the FDA group evaluating anti-depressive medications? The question is evoked most recently by the May 7 Washington Post story about drugs for depression ("Against Depression, A Sugar Pill is Hard to Beat").

Both the story and the 1999 Evidence Report/Technology Assessment (# 7) of the Agency for Health Care Policy and Research - "The Treatment of Depression: New Pharmacotherapies," of which I was an invited peer-reviewer - describe minimal differences, if any, in the effectiveness of various drugs, placebo and St. Johns Wort in the treatment of depression. Moreover the Washington Post story specifically noted that "the makers of Prozac had to run five clinical trials to obtain two that were positive, and the makers of Paxil and Zoloft had to run even more."

Dr. Thomas Loughren, "who heads the group of FDA scientists that evaluates the medicines," responds, according to the Post, by pleading ignorance: "We don't really understand psychiatric disorders at a biological level... scientists don't understand the neural mechanisms of depression." This biological approach completely ignores, however, what we do know - and have known for centuries - about the psychosocial causes for depression. While these differ considerably from one individual to another, they could be found in every depressed patient I have ever seen since starting in psychiatry in 1947.

Effective treatment must therefore be personalized, with the doctor and patient seeking together to determine the specific life-circumstances, attitudes and actions evoking the patient's current depressive reaction. This approach is almost the direct opposite of today's practice - psychiatrists ignoring patients' human situations while merely "diagnosing" and medicating them. Dr. Bernard Lown's fine book, The Lost Art of Healing, urges every physician to seek out the "aching heart" so often beating in medical patients. A psychiatry focused on drugs ignores that central imperative.

The importance of a trusting doctor-patient relationship has long been known. Dr. Kerr L. White, former Deputy Director of Research at the Rockefeller Foundation, maintains that this relationship is responsible for about half of a doctor's therapeutic impact in any medical situation. In psychiatry, that impact is probably even greater. But doctor-patient trust will not be created when a doctor ignores his patient's personal situation. And when the doctor's role becomes limited to prescribing medications, which patients often dislike, the relationship between them can become adversarial and overtly contra-therapeutic.

My response to the 1999 report concluded that this review of "pharmacotherapies of depression reveals grave scientific error in all of the studies reviewed: while focusing entirely on the supposed effects of the medication, they totally ignore the subjects' therapeutic relationships, despite the immense well-known impact of those relationships." The studies also ignored what was bothering the patients, and whether those problems were ever addressed. Clinical experience suggests that some patients, energized by medication, became better able to face relatively minor problems and overcame their depressions; with others, drugs did not help their dealing with more serious problems; and a few, facing insurmountable problems and jazzed up by medication, became homicidal or suicidal.

Given the minimal therapeutic differences among the various drugs, and since a majority of the studies of these drugs found little significant effectiveness, why were they licensed at all? Is it in the public interest to license drugs which are at most minimally better than what we already have, but also have side effects which we may not know about for years? The FDA's continued authorization of new anti-depressants, and its continued quest for biological answers to the psychosocial problems in these disorders, evokes question about whether major changes in agency approach, and perhaps leadership, are needed.