The Myth of the Magic Pill

“When money speaks, the truth stays silent.” – Russian Proverb

There is so much nonsense out there that it would take a compendium of volumes the size of Wikipedia to do it justice, but I have condensed it to three myths that permeate every aspect of mental health and the pablum fed to the public even by credible sources in the media. The last blog addressed the myth of psychiatric diagnosis.

First, before I discuss psychotropic drugs, please know that I am not anti-psychiatry or anti-psychiatric medication. Psychotropics do help some and I respect that choice when people know their options, have full disclosure of side effects, and have had a risk/benefit discussion with their provider. And some just plain prefer a pill over other alternatives. I am completely on board with honoring client/patient preferences.

What I am against is willful misinformation and marketing masquerading as science. But one more caveat before I continue. It is nearly impossible to not sound like a conspiracy theorist when you talk about the pharmaceutical industry. With unlimited resources and influence, they are indeed a formidable marketing and misinformation, profit-driven machine.  The vast reach of the pharmaceutical industry in psychotropic prescription practices, from the Internet, print, and broadcast media, direct-to consumer-advertising, ‘grassroots’ consumer-advocacy organizations, professional guilds, medical schools, prescribing physicians, and research — even into the board rooms of the FDA. Given the infiltration of industry influence, relying on press reports, web pages, and even the academic literature can be misleading.

Depression and Antidepressants

You may have noticed that despite the millions of antidepressants prescribed, they have not ended the generation gap, made economic hardship any less real, kept people from getting angry and feeling hurt, or relieved to any extent measurable, the distress of the pandemic. Drugs also will not alter in any major way the pain and disappointment inherent in relationships. Nor have they increased life satisfaction for the American public. Most importantly, the rates of “depression” and suicide, despite the millions taking antidepressants, have increased, not reduced.

One in eight Americans take them. Seventeen percent of college students take then as well as nineteen per cent of people over 60; one in five women 40-59 and one in four women over 60 are taking antidepressants. The question is are these numbers justified by the clinical trial evidence?

In the most comprehensive and detailed analyses, of all the trials submitted to the FDA for four popular SSRIs, no differences between placebo and the SSRI were found with the exception of the most distressed in the severely depressed group. And the difference there was negligible at best and  maybe attributable to patients knowing which condition they were in because of side effects as well as the study’s use of clinician-rated measures instead of patient-rated measures.

What Is Usually Reported: The New York Times

But, of course, that’s not what prescribers or the public actually believe because of articles like a recent article in the New York Times, “Antidepressants Don’t Work the Way People Think.” It starts with the now nauseatingly repetitive refrain about the “soaring” increase in rates of depression and anxiety since the pandemic (18.6% since 2020) and the corresponding increase in antidepressant prescription (see blog about ubiquitous screening).

While discussing that some researchers say the medications are barely better than a placebo and question their widespread use, the article goes on to assert, based on interviews with three psychiatrists and the results of a study discussed below, “that they do help the majority of patients that take them.” So much for investigative journalism. What about interviewing the researchers who conducted the voluminous body of work demonstrating minimal effectiveness over placebo, a far cry from helping most of those who take them? Noticeably absent from this drug company ad is any mention of the substantial troubling side effects or the significant difficulties of withdrawal.

This article outlandishly misinforms based on the STAR*D (Sequenced Treatment Alternatives to Relieve Depression), a -6-year, $35 million NIMH-funded study with nearly 2,900  participants (not counting those who dropped out before data collection) at level one examining the impact of sequenced augmentation or drug switching strategies on depression when a traditional regimen of a single SSRI failed. STAR*D was an unblinded, non-placebo-controlled trial designed to simulate conditions faced in daily practice. The sample, however, did not represent a general clinical population since it excluded those with a history of intolerance or non-response to any SSRI and included only those who preferred a medication intervention. Due to the lack of a placebo and double-blind, the authors acknowledge that “Nonspecific treatment effects [e. g., the expectation of improvement] undoubtedly accounted for some unknown proportion of the acute response or remission rates”—especially given the multistep education process that pumped participants full of anticipation of enhanced results. I won’t go into all the shenanigans of this study (e.g., inflating results by switching the primary outcome measure and including mildly depressed folks who contradicted their inclusion criteria on levels 2-4 analyses) or the substantial pharmaceutical company affiliations of the authors.

I confess that when I saw the resurrection of the STAR* D trial to justify antidepressants, my blood boiled at the misrepresentation. I know that study and the series of publications it spawned from 2004 to 2006.  Many have debunked it in the professional literature, including Dr. Jacqueline Sparks and me, but here again is the same lie, regurgitated as truth in this 2022 article without an iota of critical reflection. That study should be used as a caution about antidepressants rather than to sing their praises.

The Big Lie (not that one)

The Times article asserts that “nearly 70 percent of people had become symptom-free by the fourth antidepressant. Just a couple pages down, the expert, Dr. Gerard Sanacora, a professor of psychiatry at the Yale School of Medicine, said, “If you look at the STAR*D, better than 60 percent of those patients actually had a very good response after going through those various levels of treatment.” Total nonsense that is fully exposed in many publications. But you decide.

The average remission rate based on the primary outcome measure was 28% and 25% on the first two levels and 14% and 13% on the last two—particularly unimpressive considering the typical 30% placebo response in antidepressant trials. A true cumulative rate across the four levels, using the original primary outcome measure and correcting for those included mildly depressed participants who did not meet inclusion criteria, was 38%.

Consider how well the drugs were tolerated. At Level 1, 28% experienced moderate to intolerable side effects. At Level 2 (participants augmented or switched), 51% experienced side effects ranging from moderate to intolerable. For all levels, 24% exited due to drug intolerability. Data from the 12-month follow-up of those who either remitted or responded indicated a relapse rate of 58%.

Returning to the often-repeated numbers of “nearly 70 percent” were symptom-free and “better than 60%” had a good response reported in the Times article, here is where those numbers originate. The authors of the  STAR*D posited a 67% cumulative remission rate but qualified: “…assumes no dropouts, and it assumes that those who exited the study would have had the same remission as those who stayed in the protocol.” Wow! As the 67% figure is often repeated while the unrealistic assumptions on which it is based are forgotten, it is easy for prescribers to conclude that augmentation/switch strategies are soundly supported.

The Facts

Looking at the remission across all levels, which at each level was quite meager and less than typical placebo response, combined with a 51% adverse reaction profile after augmentation/switch, and a 58% relapse rate, a different conclusion would likely result than that of the Times article. A more critical perspective reveals that after a year of continuation treatment following remission, their data show that of the 2876 patients (some critics argue for using the number who started the trial, or 4140 participants) who started Level I, only 108 (4%) had a sustained remission — all the other patients either dropped out or relapsed.

As Medscape Medical News noted, the real results “point to a lack of long-term efficacy for antidepressants.” But the robotic repetition of the “67% effective” marketing spin is what persists—even by the New York Times.

The STAR*D authors never refuted the published exposés.  When Medscape Medical News writer Deborah Brauser asked one of the lead authors, Dr. Maurizio Fava, to comment about an extensive critical analysis, he said, “I think their analysis is reasonable and not incompatible with what we had reported.” Very telling because he agrees with the reports of the true remission rates and their sustainability. And surprisingly, he acknowledged that they knew all along, that the information was in their published account. But it took herculean efforts to wade through the subterfuge to find the real results. They know that very few will do what it takes. Science shouldn’t work that way.  But marketing does.

The point here is not to vilify the folks who take antidepressants or prescribe them or to discount those who truly benefit. Rather, the point is that when money speaks, the truth stays silent.

 Think Critically!

Don’t lose your ability to think critically about psychotropic drugs, your favorite model, and especially, your effectiveness. Better Outcomes Now helps you know whether you are really benefiting your clients.