March 1st, 2010

Antidepressants study raises questions

A dozen years ago, rumblings began that antidepressants perhaps really weren’t as effective as people thought. A 1998 analysis of 38 manufacturer-sponsored studies found that although antidepressants did help people who were depressed, they offered little more boost than did a placebo. Four years later, another analysis, this time also including unpublished studies sent to the U.S. Food and Drug Administration, suggested antidepressants offered even less of an advantage than the minuscule benefit shown in the previous report.

The latest salvo came two months ago, when another analysis published in the Journal of the American Medical Association (JAMA) indicated that antidepressants had significant benefits only in the most severely depressed patients. Though the findings are raising questions for some about the faith long placed in antidepressant medications, others say they don’t offer strong enough evidence for writing them off.

David Mischoulon, M.D., Ph.D., a psychiatrist and director of research at the Depression Clinical and Research Program at Massachusetts General Hospital, notes that the latest analysis focused on just six studies involving two medications (Paxil and Imipramine, an older tricyclic) when “there are two dozen or so antidepressants on the market.

“There are thousands of studies that have been done on antidepressants,” he says. “To go from there to saying ‘antidepressants don’t work except on people with more serious depression’ is a leap of faith. It’s completely illogical.”

Even the older meta-analyses, which included more drugs than the JAMA article, are limited because they only consider a small fraction of the research that has been done, Mischoulon says.

Some psychologists say the findings will have little impact on how they practice, as they see antidepressants as an option only after psychotherapy has been tried.

“I believe that medication is never the treatment of first choice for psychologists,” says Michael Schwarzchild, Ph.D., a clinical psychologist and director of professional affairs at the Connecticut Psychological Association. “If psychotherapy is not sufficiently effective or if it is not indicated, then a consultation regarding medication might be recommended.”

Others point out that the role of medication, even when appropriate, is limited for patients with mild to moderate depression. “My perspective is that antidepressants are a means to an end, not an end in themselves,” says Michael Formica, M.S., M.A., Ed.M., a psychotherapist in Westport, Conn. who sees patients with varying degrees of depression. Antidepressants may help someone with mild or situational depression get through a difficult period, he says, but different, non-medication strategies, whether cognitive behavioral therapy (CBT), stress management exercises, physical activity or some combination of those, will be needed to keep the gains long-term.

Some psychologists who have advocated for prescribing privileges see the findings as further evidence for the need for those privileges. “This kind of result is precisely why psychologists who are dually trained in psychotherapy techniques and psychopharmacology are ideally equipped to manage symptoms of patients,” says Sandy Rose, Ph.D., a psychologist in Dover, N.H. who had been an advocate for prescription privileges in that state. “Having a repertoire of techniques makes us much less likely to use a hammer approach to a problem, and instead, tailor therapy to what empirically works best.”

Dual training would enable psychologists to facilitate treatment for patients, Rose adds. “As psychologists are trained in understanding and implementing clinical research at the doctoral level, they are also highly adept at understanding research such as this and applying it to practice.”

In raising skepticism about antidepressants, the analyses may help to highlight other options for depression treatment.

“I think it is very important for clinical psychologists and other healthcare providers to integrate these recent findings into their thinking about treatment recommendations,” says Greg Feldman, Ph.D., an assistant professor of psychology at Simmons College who researches psychotherapy and self-management approaches for depression. “These and many previous studies do support the use of antidepressant medication for severe depression; however, applying an empirically-supported psychotherapy might also be an appropriate first-line treatment for these patients.”

Feldman, who co-authored a book called “Self-Management of Depression,” says studies have shown cognitive-behavioral therapy (CBT) to be as effective as medication, even for some patients with severe depression. Evidence suggests that CBT may be more effective than medication in preventing relapse after treatment has ended, he says.

For patients with less severe depressive symptoms, physical exercise or bibliotherapy are two self-management approaches that have been shown to be helpful alternatives to medication, he adds.

Among the challenges of finding the best treatment for patients is identifying those who are most likely to respond to antidepressants. Depression resulting from a biochemical imbalance is more likely to be lifted by an antidepressant than is situational depression, Mischoulon says. Possibly clouding studies of antidepressants is that while older studies were conducted on severely depressed, hospitalized populations, recent studies likely include people with less severe depression.

Distinguishing situational depression from one caused by biological factors is not always easy, Mischoulon acknowledges, particularly because biological depression can come in milder variations. (His research team has developed an interview to help tell the two apart).

“Depression is a collection of symptoms,” he says, “but the DSM doesn’t account for the underlying causes of these symptoms. It’s like looking at the tip of the iceberg.”

By Ami Albernaz

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