Psychful

For some reason the “controversial” article published in The Journal of the American Medical Association (JAMA) in January 2010 has not had much effect on the practice of prescribing medications for depression. In summary, the JAMA study reported:

“Antidepressant medications represent the best established treatment for major depressive disorder, but there is little evidence that they have a specific pharmacological effect relative to pill placebo for patients with less severe depression.”

A fairly rigorous study published in one of the most prestigious medical journals tells us that antidepressants are the way to go even if they are no better than sugar pills. With US sales rising to nearly $10 billion in 2009, it is clear that antidepressants are here to stay despite being what Sharon Begley of Newsweek has called “expensive Tic Tacs”. Despite Irving Kirsch’s 1998 and 2002 studies revealing antidepressants were only marginally better than placebo, the number of Americans taking antidepressants doubled from 1996 to 2005. Science is rarely deterred by conflicting evidence when billions of dollars are at stake.

Ask most television viewers what causes depression and you are likely to get a reply that mimics the ubiquitous ads run by the pharmaceutical industry: it’s a chemical imbalance in the brain that needs to be corrected with medications. This theory, which dates back to the 1960s, has changed little over the years and continues to drive the search for medications to treat depression. And it is wrong.

As Kirsch and others have shown, the chemical imbalance theory of depression is only a “useful metaphor”, a phrase attributed to Wayne Goodman while chair of the FDA psychopharmacologic advisory committee in 2005. If depression is the result of low levels of the neurotransmitter serotonin, as is suggested by popular SSRI antidepressants like Prozac, then why does the French antidepressant Stablon (tianeptine) work equally well by lowering serotonin levels in the brain?  You can’t have it both ways.

Kirsch makes a good case that whatever benefit is realized by taking antidepressants can be explained as being a placebo effect.  All FDA-approved medications must be shown to be more effective than an inert placebo (sugar pill) in at least two trials in order to receive the FDA’s seal of approval.  Kirsch’s studies reveal that antidepressants barely meet the mark when the studies are carefully examined.

What none of the pharmaceutical studies are required to do is show a benefit over an active placebo. If you give one group of depressed patients an antidepressant and another group an inert placebo, only one group is likely to respond with side-effects. But if you give one group an antidepressant while giving the other group an active placebo, like an antihistamine which causes side effects but has no antidepressant properties, the antidepressant won’t show any benefit over the placebo. Side effects tell the subjects in the study they got the “real” pill, and they are more likely to report “real” benefits.

The truth is we are not yet clear on what causes depression and so we are limited in our methods to correct the condition. The stress model of depression has been recently challenged in animal studies at Northwestern while further debunking the chemical imbalance theory of depression. Only further research and critical thinking will enable us to break free of the dominant theoretical models promoted for financial gain by a wealthy pharmaceutical industry. Who else can afford to pay for research like this? In the mean time, we will likely follow the advice of Adolph Hitler: “If you wish the sympathy of broad masses then you must tell them the crudest and most stupid things.”  Hold on, America.