Peter Brown, clinical professor of psychiatry at Brown University and a prominent mental health hero of mine, published an excellent piece in Sunday’s issue of The New York Times. As he has done in the past, he successfully debunks the debunkers. I think he’s improving at his game as the assaults against antidepressants grow more fierce and numerous.

Now, mind you, I consider myself very conservative when it comes to psychoactive (or psychopharmaceutical) drugs. Having been overmedicated by more than one psychiatrist in the past, I am of the opinion that a person should throw everything she has at her mental health (intense cardiovascular exercise, Omega-3 capsules, meditation and/or prayer, regular psychotherapy, a healthy diet, good sleep hygiene, light therapy, service work, and community involvement—yes, all of those) before considering antidepressants. A better diet and exercise alone may be able to repair neural circuits and brain chemistry for someone with situational or mild depression.

However, when you are dealing with the “I want to be dead” thoughts a few times every hour for months on end—and are working like hell at achieving some kind of balance in your life with the help of all the other alternative therapies—I am of the opinion that the risks of toughing it without meds outweigh the risks of taking meds when you stop to consider the increased chances a depressed person has of developing cardiovascular disease and heart attacks, the compromise to her immune system making her three times more likely to catch a cold or something worse, like shingles. And let’s not forget the devastation and disruption depression produces in a marriage and on the emotional well-being of children.

With so much literature out these days on the weak effect of antidepressants—that these medicines are no more effective than placebos–and endless reports about Big Pharma’s manipulation of drug trials, it’s difficult for the average person to feel good about taking antidepressants—even if the death thoughts occur so frequently that she has difficulty functioning at her job and making dinner for her kids.

This is where my hero, Peter Kramer, comes in … to fill in all the details that the prominent stories about antidepressants conveniently leave out. Kramer writes:

Could this be true? Could drugs that are ingested by one in 10 Americans each year, drugs that have changed the way that mental illness is treated, really be a hoax, a mistake or a concept gone wrong?

This supposition is worrisome. Antidepressants work—ordinarily well, on a par with other medications doctors prescribe. Yes, certain researchers have questioned their efficacy in particular areas—sometimes, I believe, on the basis of shaky data. And yet, the notion that they aren’t effective in general is influencing treatment.

Kramer goes on to dissect one such popular piece of research—the study that was covered in the Newsweek article awhile back (which argued psychopharmaceutical drugs were no more effective than a placebo) and the recent New York Reviews articles by former Editor in Chief of The New England Journal of Medicine Marcia Angell. The examination uses data submitted to the Food and Drug Administration in the late 1980s and the 1900s that was ill suited to answer questions about mild depression. Why? Often in FDA studies, subjects are included who do not suffer from depression. Moreover, companies that are in a hurry to get medications to market have motivation to run quick, sloppy trials. So it’s no wonder, then, that a few weeks down the road these subjects are free of depressive symptoms. Also, to get free care or incentive payments offered as part of the study, some people may exaggerate their symptoms.

Kramer probes another study by psychologist Robert DeRubeis, which graced the headlines of a USA Today piece, titled “Antidepressant lift may be all in your head.” Kramer explains:

Dr. DeRubeis, an authority on cognitive behavioral psychotherapy, has argued that the washout method plays down the placebo effect. Last year, Dr. DeRubeis and his colleagues published a highly specific statistical analysis. From a large body of research, they discarded trials that used washouts, as well as those that focused on dysthymia or subtypes of depression. The team deemed only six studies, from over 2,000, suitable for review. An odd collection they were. Only studies using Paxil and imipramine, a medicine introduced in the 1950s, made the cut — and other research had found Paxil to be among the least effective of the new antidepressants. One of the imipramine studies used a very low dose of the drug. The largest study Dr. DeRubeis identified was his own. In 2005, he conducted a trial in which Paxil did slightly better than psychotherapy and significantly better than a placebo — but apparently much of the drug response occurred in sicker patients.

Building an overview around your own research is problematic. Generally, you use your study to build a hypothesis; you then test the theory on fresh data. Critics questioned other aspects of Dr. DeRubeis’s math. In a re-analysis using fewer assumptions, Dr. DeRubeis found that his core result (less effect for healthier patients) now fell just shy of statistical significance. Overall, the medications looked best for very severe depression and had only slight benefits for mild depression — but this study, looking at weak treatments and intentionally maximized placebo effects, could not quite meet the scientific standard for a firm conclusion. And yet, the publication of the no-washout paper produced a new round of news reports that antidepressants were placebos.

In the end, the much heralded overview analyses look to be editorials with numbers attached. The intent, presumably to right the balance between psychotherapy and medication in the treatment of mild depression, may be admirable, but the data bearing on the question is messy.

Much like I, Dr. Kramer is by no means a pill-pusher. In his 1993 bestseller, “Listening to Prozac,” he wrote, “To my mind, psychotherapy remains the single most helpful technology for the treatment of minor depression and anxiety.” He believes that drugs are “permissive,” in that they remove the roadblocks to self-healing. I absolutely concur. The role of medication in my own recovery is to stabilize me enough that I can use all my other tools with more effectiveness. Psychotherapy is no good if you don’t have the concentration to have a dialogue with your therapist.

Kramer doesn’t argue that antidepressant treat all ranges of mood disorders alike—from mild, situational depression to severe major depression. He believes that drugs work best to combat the “stuckness” in a person’s brain that is preventing resiliency. His hope for future research is to identify this “stuckness” with more accuracy so that doctors know when antidepressants should be included in treatment. Says Kramer:

Better-designed research may tell us whether there is a point on the continuum of mood disorder where antidepressants cease to work. If I had to put down my marker now — and effectively, as a practitioner, I do — I’d bet that “stuckness” applies all along the line, that when mildly depressed patients respond to medication, more often than not we’re seeing true drug effects. Still, my approach with mild depression is to begin treatments with psychotherapy. I aim to use drugs sparingly. They have side effects, some of them serious. Antidepressants help with strokes, but surveys also show them to predispose to stroke. But if psychotherapy leads to only slow progress, I will recommend adding medicines. With a higher frequency and stronger potency than what we see in the literature, they seem to help.

My own beliefs aside, it is dangerous for the press to hammer away at the theme that antidepressants are placebos. They’re not. To give the impression that they are is to cause needless suffering.

As always, Dr. Kramer, thank you.

Image courtesy of Wikimedia Commons.

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