Welcome to From Insults to Respect. Regular readers know that from time to time I address concerns about the use of antidepressants in our society. Well, as I was thinking about what to write about this week’s post, I learned of a new meta-analysis that was published in the medical journal Lancet that appears to support the claim that antidepressants are effective, at least in short-term studies.

Although well thought out critiques of this analysis soon appeared, the power of the pharmaceutical industry’s media promotion apparatus will lead to the public hearing far more readily a simplified version of the Lancet findings. And so, out of respect for the public’s right to make informed choices, I have decided to provide my readers the link to one of the most thorough and readable critiques (see HERE).

Robert Whitaker

It’s written by Robert Whitaker, a medical writer who started out as a Knight Science Journalism fellow at MIT. Following that, he became director of publications at Harvard Medical School. His most recent book is Anatomy of an Epidemic.

In addition to providing the link to Whitaker’s critique, below I provide a brief summary of his critique’s main objections to the conclusions of the Lancet article. As you will see, there exists substantial evidence that rather than improving outcomes for people dealing with the challenging experiences of depression, antidepressants actually tend to worsen outcomes. The studies I refer to below are fully referenced in Whitaker’s article.

A Brief Summary of Robert Whitaker’s Critique

Whitaker tells us that the Lancet analysis relies on random control trials (RCT) that compared depressed patients taking a placebo with those taking the antidepressants over a mere eight weeks. After eight weeks, symptom reduction, as measured in this study, did favor those in the groups that took the real drug. Should that be the whole story?

Whitaker rightly points out that RCTs are fraught with problems. Most of the studies are industry-funded, thus investigator bias is a worry. The placebo group is composed of patients who have been abruptly withdrawn from antidepressants that they had been taking before the trials got underway, which isn’t a true placebo group at all. Rather, they are a special group of depressed individuals likely to be suffering withdrawal reactions.

Upon looking at the risks versus benefits from this symptom-reduction data, Whitaker tells us that even if we assume that the results are accurate, then:

“12% of patients will benefit from the treatment, while the remaining 88% will suffer the adverse effects of treatment without any additional therapeutic benefit beyond placebo. Those are the odds that a person contemplating taking an antidepressant drug might want to know.”

Whitaker goes on from here to point out that the RCT studies use eligibility criteria to select participants most likely to respond well to the drug. Only about 10% to 30% of real-world depressed patients meet these criteria. Do real world patients respond differently?

In one study that looked at this, only 19% had responded to the treatment at three months, which was one-third the response rate recorded in RCTs. In another study known as the STAR*D trial, this one hailed as the largest antidepressant study, patients who didn’t respond to a first round of treatment could then have a second round with a different antidepressant, and so on through four courses of treatment. The idea was that eventually a treatment would be found that would work. Yet, even with this design, the short-term findings indicated only 38% of the 4041 patients reached meaningful improvement as defined by the researchers.

Whitaker’s conclusion about the effects of antidepressants as determined from the two major short-term studies on real world patients follows:

“Are they better than “natural recovery” rates over the short term? I am not sure there is a good answer to that question in the research literature, but what can be concluded from these two studies is that there is a lack of evidence that antidepressants are effective in the majority of real-world patients, even over the short term. They “work” in only a minority of patients, and it may be that they don’t provide any benefit over natural recovery rates at the end of 6 to 12 weeks.

As interesting as these studies are, it is perhaps even more important to look at the effectiveness of these types of drugs beyond 12 weeks. After all, the goal for people who are depressed is to get well and stay well. In research terms, patients want to experience a “sustained remission.” Whitaker’s critique extensively reviews the studies bearing on this, and the results are troubling.

In one study with real-world patients, 13% were in remission at the end of the year, but only 5% had a “sustained remission” during the year. The outcomes in this study, according to John Rush, the lead researcher in the study, “reveal remarkably low response and remission rates.”

The documented stay-well rate in the STAR*D trial was even worse. At the end of one year, only 108 of the 4041 patients (3%) had remitted and stayed well and in the trial. All of the others had either failed to remit, relapsed, or dropped out of the study.

A Minnesota report on the real-world outcomes of 260,000 patients treated for depression from 2010 to 2013 found similarly low remission rates. At the end of each year, only about 5% of the patients were in remission. Another 10 percent or so were still considered responders to antidepressant treatment.

How does this compare to people who are depressed but don’t take antidepressants? Whitaker describes the following study that seeks to answer this question:

In 2006, Michael Posternak, a psychiatrist at Brown University, studied the one-year remission rate for unmedicated patients. To do his research, he identified 84 patients enrolled in an NIMH study who, after recovering from an initial bout of depression, subsequently relapsed but then did not go back on an antidepressant. He tracked their remission rate over time: 23% percent had recovered by the end of the first month; 67 percent at the end of six months; and 85% at the end of one year.

Posternak summed up his results in this way: “If as many as 85% of depressed individuals who go without somatic treatment spontaneously recover within one year, it would be extremely difficult for any intervention to demonstrate a superior result to this.”

These results are quite startling. In the Minnesota study, only 5% of those taking antidepressants were viewed as recovered at the end of one year while in the Pasternak study 85% of those not taking an antidepressant recovered in the same time period. Although definitive conclusions can not be made from just two such studies, the findings do raise the question, do these types of drugs worsen outcomes for people dealing with depression experiences?

Exploring this issue further, Whitaker takes a close look at the few longer term studies that used real world patients. He tells us:.

• In a retrospective study of the 10-year outcomes of 222 people who had suffered a first episode of depression, Dutch researchers reported that 76% of those not treated with an antidepressant recovered and never relapsed, versus 50% of those initially prescribed an antidepressant.
• In a Canadian study that charted outcomes for 9,508 depressed patients for five years, those taking antidepressants were depressed on average 19 weeks per year, versus 11 weeks for those not taking antidepressants.
• In a World Health Organization study designed to assess the merits of screening for depression, which was conducted in 15 cities around the world, the patients who were diagnosed by their GPs and treated with an antidepressant were twice as likely to be depressed at the end of one year as those who weren’t diagnosed and treated, even though their baseline depression scores were nearly the same.
• This WHO study also provided some insight into the effectiveness of antidepressants—or their lack of effectiveness—over time. At the end of three months, the patients treated with medications had improved slightly more than the unmedicated group, but after that time they stopped getting better, while the unmedicated group continued to improve throughout the year.
• In a study of 1,281 people who went on short-term disability in Canada due to depression, 19% of those who took an antidepressant failed to return to work and went on long-term disability, compared to 9% of those who didn’t fill a prescription.
• An NIMH-funded study assessed the six-year “naturalistic” outcomes of 547 people who suffered a bout of depression, and found that those who were treated for the illness were three times more likely than the untreated group to suffer a “cessation” of their principal social role, and nearly seven times more likely to become incapacitated.
• The burden of depression in developed countries around the world has dramatically increased since Prozac arrived on the market in 1987.  A 2015 study found that the economic burden from depression in the United States increased from $83 billion in 2000 to $210 billion in 2010.
• There has been a dramatic increase in the number of people on disability due to mood disorders in developed countries during the Prozac era, with this increase happening in lockstep with the increased prescribing of antidepressants.

Whitaker concludes with these words:

I think it is fair to conclude, based on this data, that antidepressants, as they are used now, can’t be said to “work” for society. Instead, they can be said to cause significant societal harm.

Now, I hasten to point out that for people experiencing depression, their choices are not merely either taking an antidepressant, a placebo, or no treatment at all. Many people report great help from psychotherapy and counseling, although the cost can be unrealistic for many. With regard to learning how to positively deal with the emotional pain that is a central feature of the depression experience, there are several effective approaches that don’t cost any money, such as sensory focus, expressive writing, and meditation. I describe these approaches HERE. Exercise such as walking, yoga, etc, have not only been found in scientific studies to be helpful, but enhance other health outcomes as well.

One of the most frustrating aspects of taking drugs like antidepressants, is that the prescribing doctors often don’t explain how difficult it is for many people, once they begin taking them, to come off them. People can experience severe withdrawal effects that can last for months. Learning how to safely ween off of them can be a challenge. Just stopping them, cold turkey, has the potential to be dangerous for some. There are people, however, who can help you through this challenging experience (see HERE for recommendations).

Some people will enjoy reading this blog by beginning with the first post and then moving forward to the next more recent one; then to the next one; and so on. This permits readers to catch up on some ideas that were presented earlier and to move through all of the ideas in a systematic fashion to develop their emotional and social intelligence. To begin at the very first post you can click HERE.

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