Are Antidepressants Any Better Than A Sugar Pill?

Depression, or Major Depressive Disorder, affects about 7 percent of adults in the United States annually.  It is the leading cause of disability in the 15-44 age group, according to statistics from the National Institute for Mental Health.  Recent data from the Centers for Disease Control and Prevention (CDC) show that drugs to treat depression, or antidepressants, are the most commonly prescribed drugs in the US. That means that antidepressants are prescribed more than drugs to treat heart disease, diabetes, asthma and other diseases.  In 2005, there were 118 million prescriptions written for antidepressants in the US.  This reflected a tripling of these prescriptions bewteen1988-1994 and 1999-2000. According to data cited in the Washington Post, these prescriptions came at a cost of almost 10 billion dollars in 2008.

But are these drugs actually doing any good?

An analysis published in this week's Journal of the American Medical Association (JAMA) questions the efficacy of antidepressants for many patients. 

The study is a meta-analysis, essentially a grouped analysis of data from several studies.  It looked at studies published from January 1980 through March 2009 and included only the most scientifically rigorous studies, randomized, placebo controlled trials using an FDA approved antidepressants in the treatment of depression in adults.  The studies included used a standardized questionnaire to rate the severity of the patients' depression, the Hamilton Depression Rating Scale.  In essence, these studies compared antidepressants to placebo, or sugar pill, in patients with varying severity of depressive symptoms. There are thousands of controlled clinical trials of antidepressant use over the last 50 years that have shown that antidepressants are helpful in treating depression, but this new analysis is unique in rigorously breaking down the data by degree of depression.

What did the authors find? Their analysis suggests that many commonly prescribed antidepressants may be no more helpful than a placebo, except in cases of severe depression.

The authors of the study reviewed trials of two antidepressants, paroxetine (Paxil) and imipramine (Tofranil).  Paroxetine belongs to the class of medications called SSRIs (Selective Serotonin Reuptake Inhibitor).  Other commonly prescribed SSRIs include fluoxetine (Prozac), citalopram (Celexa), escitalopram (Lexapro), and sertraline (Zoloft). Imipramine is from one of the oldest classes of antidepressants, the tricyclic antidepressants (TCAs).  

The researchers found that, compared with placebos, these drugs caused a much steeper reduction in symptoms of severe depression only  (cases scoring in the top quarter of the sample). Patients with less than severe depression got little or no added benefit from the medications, and the degree of benefit increased proportionately to the severity of their patients' depressive symptoms.  The most depressed patients did get substantial improvement with treatment with these medications.

Limitations: because of the stringency of the criteria used for selecting these studies, the number of studies and of patients included in this analysis was relatively small. In total, data from 6 studies (718 patients) were included.  Furthermore, the depression symptom questionnaire used, while the one most commonly used in clinical practice, may not be a perfect measure of depression severity.  The study only looked at two drugs.  However, the SSRIs are the most commonly prescribed antidepressants and are similar enough to one another that the studies of paroxetine can likely be applied to all SSRIs.  Finally, the study looked at the effect of treating depression initially or acutely, and not long-term or maintenance treatment.

These possible limitations aside, though, this analysis raises a critical eye at how depression is most commonly treated, with antidepressants.The authors concluded, "Prescribers, policy makers, and consumers may not be aware that the efficacy of medications largely has been established on the basis of studies that have included only those individuals with more severe forms of depression" and that this fact is "not reflected in the implicit messages present in the marketing of these medications to clinicians and the public."

For people with more moderate symptoms of depression, this analysis suggests that treatments other than antidepressants may be equally helpful.  The alternatives include psychotherapy and supportive care such as nutrition, exercise, sunshine, and rest.

*  *  *

The abstract of the original article can be found at: 

http://jama.ama-assn.org/cgi/content/short/303/1/47?home

Fournier, JC, DeRubeis, RJ, et al.  Antidepressant Drug Effects and Depression Severity: A Patient-Level Meta-analysis.  JAMA 2010; 303(1):47-53