PROBING THE PLACEBO EFFECT

Nayer Khazeni, M.D.
Friday, March 21, 2008

This article appeared on page P - 5 of the San Francisco Chronicle

The CDC reports that antidepressant use by American adults tripled from 1988 to 2000, but two recent studies in peer-reviewed journals show that for the majority of these patients, the most commonly prescribed antidepressants work no better than sugar pills.

Is this information new? Yes and no. The investigators of these studies had to legally invoke the Freedom of Information Act to obtain and analyze unpublished trials on SSRIs (selective serotonin reuptake inhibitors - the most commonly prescribed class of antidepressants, which include Prozac, Zoloft and Paxil). They discovered the existence of a "file drawer effect" - trials with positive results are published while others are filed away - an issue that may confuse the true results of a great deal of medication research.

The January 2008 New England Journal of Medicine investigators found that 37 of 38 studies of antidepressants with positive results were published, whereas only 14 of 36 studies with negative or questionable results were. Even among those 14, many did not emphasize that suicidal thoughts and hopelessness persisted, highlighting, for example, improvements in sleep and energy, instead. The reversal of such "vegetative" symptoms (lethargy, insomnia and poor appetite) of depression in the presence of a continuing depressed mood is thought to play a role in the risk of completing suicide, and the FDA now requires all antidepressants to carry the most serious "black box" drug warning regarding possibly increased suicide risk.

The February 2008 Public Library of Science investigators, studying a different group of SSRIs, statistically analyzed the combined results of published and unpublished trials. Their findings added to several other studies showing that in all but the most seriously depressed patients, those who get better with antidepressants may also improve with placebos (sugar pills). This "placebo effect" is not unique to mental health treatment: From responses to placebo pills for the common cold to placebo operations for knee osteoarthritis, such improvements demonstrate the remarkable ability we have to heal our own minds and bodies without using pills.

If you're wondering about studies showing decreases in serotonin and other neurotransmitter levels in depressed or anxious people, be careful not to confuse those for evidence of a genetic basis for depression or anxiety or the need for a chemical solution. Serotonin levels can decrease in someone with no genetic predisposition to depression when he's upset about not having made partner at his firm, and can increase with just a few minutes of brisk walking. In fact, a wealth of data now verifies that depression and anxiety symptoms and biochemical markers improve with measures like exercise, meditation or talk therapies.

Before considering any therapy, be sure you and your physician have had enough time together to determine if you meet criteria for medical depression or anxiety (these disorders are closely linked, and antidepressant medications are used to treat both). Sadness or nervousness are not reason enough to begin a course of SSRIs or any therapy with multiple drug interactions and potentially serious side effects - those are normal human emotions, and in some cases, our bodies' protective warning signals to make a change in our lives.

Dr. Nayer Khazeni specializes in internal medicine and pulmonary/critical care, teaches and conducts research at Stanford University Medical Center.

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