Wednesday, January 04, 2006

How Effective Are Antidepressants?

A growing body of scientific evidence suggests that antidepressant drugs are only modestly effective, probably much less so than you realize. Unfortunately, these medications just don't live up to the hype.

An eagerly awaited landmark study published in the American Journal of Psychiatry this week makes the point quite clearly. Researchers followed 2,876 depressed patients at 41 different clinics while they were treated with Celexa (citalopram) - one of the best-selling depression medications, and a close chemical cousin of drugs like Zoloft, Prozac, Paxil, and Lexapro.

According to researchers, after 10 weeks of treatment:
Remission rates were 28% [based on clinicians' ratings] and 33% [based on patients' ratings].

This means that fewer than 1 in 3 patients recovered on Celexa, regardless of whether we look at the patients' own ratings of their symptoms or those of their clinicians.

It gets worse.

Patients in this study got much better care than the vast majority of patients "in the real world." They saw their doctors every couple of weeks - much more frequently than almost any insurance plan will cover. Their doctors also carefully evaluated medication levels at each visit, and increased dosage if the meds didn't seem to be producing an adequate response at the initial dose (again, this doesn't happen as efficiently in real world settings). Thus, by the end of the treatment period, the average dose was about 50mg per day - a higher dose than most patients will ever take (typical starting dose is 20mg).

Finally, the study's 28% response rate is actually an over-estimate, since it excludes the many patients who quit taking the meds right away (i.e., before they completed their first followup evaluation) as well as those who were switched by their doctors to a different drug for any reason (e.g., intolerable side effects).

Bottom line: The great majority of patients who take antidepressant medications do not experience a complete and lasting cure of their depression. This is why, for example, the epidemic of depression in the U.S. keeps getting worse (the lifetime prevalence of depressive illness is now nearly 25%) despite the millions of prescriptions dispensed each week.

I truly wish it were otherwise. And if you happen to be one of those who have benefited enormously from taking an antidepressant medication (as a practicing clinician, I've seen many), then know that I rejoice with you . . . if only it happened more often.

In posts to follow, I'll discuss what the research literature has to say about more effective and enduring treatments for depression.


Dr. Deborah Serani said...

I have to agree professionally with this estimate as I'm sure you do as well. Personally,I am fortunate that my first trial of meds was wonderfully successful and my symptoms were and continue to be significantly reduced. We know so much and yet we know so little. Future research and technology will be amazing I hope.


Psych Pundit said...


I'm delighted to hear about your superb response to meds . . . though it's clear from all the research that you're in the minority in that respect.

Fortunately, there are numerous other adjuvant therapy strategies (aerobic exercise, omega-3 supplementation, light therapy, anti-rumination techniques, etc.) that can enormously improve a person's odds of recovery.

Best wishes.

Dr. Deborah Serani said...

Vagus Nerve Stim too. I'm doing a post about that now. BTW, I "googled" and APA'd you, and wow, you are one prolific researcher and writer. So glad to have you out there!

OK back to work for me now.

Psych Pundit said...


Thanks for the kind words - that made my day!

By the way, I'm not yet convinced about the efficacy of vagus nerve stimulation (aside from the large and formidible placebo effect that it likely induces).

Here's a relevant abstract to consider:

Expert Rev Med Devices. 2004 Sep;1(1):155-60. Related Articles, Links

VNS and depression: current status and future directions.

Walsh SP, Kling MA.

Department of Neurology, Georgetown University Medical Center, Washington, DC 20057, USA.

Vagus nerve stimulation (VNS) is an established anticonvulsant therapy in treatment-resistant patients with epilepsy. The known anatomical projections of the vagus nerve to many brain regions that have been implicated in mood disorders suggest that VNS may also have useful antidepressant effects. There has been growing interest in the potential application of VNS in the nonpharmacological management of treatment-resistant depression. Results from an open-label study, in which 59 subjects with treatment-resistant depression were treated for 10 weeks with VNS therapy, reported a 31% response rate. In a recent controlled double-blind trial of VNS and depression, short-term treatment for 10 weeks failed to demonstrate statistical improvement over sham treatment. Results from the long-term phase of this trial may be more significant, however published data are awaited.

Michael Andreyakovich said...

The difficulty with such studies is they leave a door wide open for all kinds of condemnation, accusations of malpractice, sinister whisperings about irresponsible doctors recklessly over-prescribing for their patients, not to mention paranoid conspiracy theories about how psychotherapy/psychiatry/the-study-of-the-mind-in-general is all a big scam to control and defraud the patient. These people are the worst of the lot, but they're not the only ones out there.

Psych Pundit said...


Although such studies can certainly be misinterpreted (as you suggest), this sort of research is crucial to answering the question we all need to have answered: which treatment(s) are most effective for each disorder? Without solid empirical evidence, we're all at the mercy of the slick sales pitch.

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