Are Antidepressants Merely Providing a Placebo Effect? | AAFP

to the editor: We appreciated the recent review of pharmacologic management options for adult depression, which addressed many important issues that family physicians face. Depression is a major health issue associated with morbidity and loss of productivity. In 2007, antidepressants ranked as the top class of medications dispensed in the United States, with an estimated 232.7 million antidepressant prescriptions and an estimated sale of $11.9 billion.1 However, a recent meta-analysis suggests that selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may not be more effective than placebo.2 Selective publication of positive studies appears to have greatly overstated the benefits of these drugs.3
Although we have regularly witnessed apparent benefits of SSRIs and SNRIs in patients with depression, family physicians should also recognize the limitations of data regarding these drugs and call for further research and discussion. Could the dramatic responses to antidepressant medications be a placebo effect in which providers actively listen and patients feel understood, gain insight, believe in their treatment plan, feel motivated to change their lifestyle or social situation, or perhaps some combination?4 Should we reintroduce the N-of-1 trials, in which each patient is their own “study” comparing placebo with active medication over some period of time, in order to identify the small proportion of patients who may benefit from SSRIs or SNRIs?
The majority of depression studies measure changes in depression scores that have uncertain clinical significance. Remission rates are rarely measured, and most studies are of short duration (often as little as 24 weeks of follow-up). We need to help researchers identify outcome measures that are more meaningful in the primary care setting.
Perhaps physicians should prescribe SSRIs and SNRIs only after fully disclosing to their patients that the drugs may be acting through the placebo effect and sharing the known side effects.5,6 Clearly, more research is needed. We think it is time to find out if there are better ways to treat depression.
in reply: We appreciate Dr. Grossman's input regarding the risk of hyponatremia with use of selective serotonin reuptake inhibitors (SSRIs) and about the use of antidepressants during pregnancy and breast feeding. The complicated issue of managing depression during pregnancy and the postpartum period is a worthy topic for a separate review.
The letter from Drs. Baghdady, Goo, and Mayer raises important concerns regarding the quality of evidence supporting the efficacy of antidepressants in patients with major depression. The number of studies on this topic is astounding. PubMed indexes 4,750 papers related to clinical trials of anti-depressive agents. However, antidepressant trials are typically industry-sponsored and short in duration. The issue of publication bias raises worrisome issues about drawing conclusions about efficacy and harms solely from published data. Although we disagree with the conclusion that antidepressants are no better than placebo, we do agree that large, well-designed, long-term studies are needed to fully elucidate when and how anti-depressants should be used.
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