AJP Board Member Responds to NYT Story On Antidepressant Withdrawal

A New York Times article on long-term use of antidepressants “invites readers to make fallacious jumps connecting islands of truth in pursuit of a titillating, and stigma-perpetuating, theory: psychiatric disease and the suffering it brings are a failing of character best addressed through clean living or perhaps cleansed with redemptive suffering.”

So wrote Roy Perlis, M.D., M.Sc., a member of the Editorial Board of the American Journal of Psychiatry (AJP), in a hotly critical editorial published just 18 days after the Times published its article under the headline, “Many People Taking Antidepressants Discover They Cannot Quit.”

The AJP editorial faults the Times article for at least two large errors: deploying public health data about the growth in antidepressant use in tandem with anecdotal reports about severe problems with withdrawal from medications (what Perlis calls an “ecological fallacy”) and then painting those anecdotes as darkly illustrative of a couple of known realities (those “islands of truth”)—namely, that some patients experience withdrawal requiring lengthy tapers and that there is a need for more and better data on the long-term use and safety of antidepressants.

Given that the article was published in a respected news outlet with an international reputation, it could have serious consequences for people with depression, Perlis told Psychiatric News.

“A reasonable person struggling with depression who read that article might say, ‘I should not get treatment that includes antidepressants,’ ” he said. “That would be exactly the wrong message to take away from that article, but it’s easy to see how someone might.

“For all the progress that has been made in conveying to people that depression is an illness that is diagnosable and for which there is a range of treatments—for all that progress, the amount of damage that an article like this can do is profound. For clinicians and researchers who spend the bulk of their time trying to improve treatment of depression, to see those efforts set back however unintentionally is infuriating and requires a response.”

The response was fast—almost lightning fast in the world of peer-reviewed medical journal publishing. “It’s a reflection of the urgency that we saw in responding to this,” Perlis said.

He said the Times article generated enormous “buzz” among psychiatrists, including members of the AJP Editorial Board, and a decision was made to write a response. AJP Editor Robert Freedman, M.D., turned to Perlis, who is director of the Center for Quantitative Health at Massachusetts General Hospital and a professor of psychiatry at Harvard Medical School. (The editorial notes that he has received consulting fees from or served on scientific advisory boards for Genomind, Psy Therapeutics, and RID Ventures, and he holds equity in Psy Therapeutics.)

“I am grateful to Dr. Perlis, an associate editor of the Journal, for his immediate response to a call for a commentary addressing the New York Times article on antidepressant use,” Freedman told Psychiatric News. “Discounting the effectiveness of antidepressants is a disservice to patients who can benefit from their appropriate use. We have expedited the publication of his commentary to provide families, patients, and clinicians with a more balanced view of the issue.”

Freedman said AJP has commissioned articles that propose longer-term efficacy and safety studies and that provide clinicians with current information on indications and safety for withdrawal after longer term use.

In his editorial, Perlis offered clarity regarding those “islands of truth” the Times tried to connect.

First, the matter of withdrawal. “Factually, as the article acknowledges, withdrawal syndromes have been recognized from the beginning of the modern psychopharmacologic era,” he wrote.

“For this reason, slow, systematic tapers—when necessary, incorporating longer half-life antidepressants—represent a standard of care. And many clinicians will recognize in their practice some of the phenomena noted in the article, such as patients requiring very long tapers of medications. Clinicians will also recognize that in some cases, such symptoms actually represent recurrence of depressive, anxious, and somatic symptoms—the indication for treatment in the first place. That patients are able to sustain long-term treatment is testament to half a century of work on tolerability.”

In an interview with Psychiatric News, Perlis noted as well that the Times had written about patients who had experienced extreme difficulty withdrawing from antidepressants—something he said existing data suggest is extremely rare.

Then there is the matter of the relative paucity of long-term data. “The article is also undeniably correct that we know far too little about long-term consequences of antidepressants—and nearly every medication in common use in medicine,” Perlis wrote. “That antidepressants are singled out may reflect a unique degree of discomfort with medications that affect the brain, but the big picture reminds us that all medications have off-target or longer-term impact that cannot be captured in the regulatory approval process.”

Perlis also pointed out that the Times article appeared just one week after a meta-analysis in Lancet based on data on more than 100,000 individuals demonstrated (not for the first time) that antidepressants are generally similar to one another in efficacy and are consistently superior to placebo. “Yet media accounts still routinely treat antidepressant efficacy as an open question and toxicity as a near certainty,” he wrote.

Finally, he said, the editorial is a call to action. “I don’t want people to come away with the idea that our work is done,” he said. “We do need more long-term data. Let’s use this as an opportunity to learn more about long-term safety and about discontinuation and problems that may be associated with it.”

So what’s the message clinicians should give to patients who may have read the Times article?

“The message should be one of reassurance—that we do know a lot about long-term safety though we need to know more,” he said. “We have hundreds of millions of years of patient data, and we know these medications are safe. Does that mean there can’t be rare serious outcomes? No, but that is no different from any other drug on the market.” ■