Antidepressants and Placebo: Voices Split on Effectiveness

Photo by Brian K. Binford


Who knows why you feel well?

Currently, 17 million Americans take some form of Selective Serotonin Reuptake Inhibitor (SSRI) antidepressant, like Prozac, which was introduced in the late 1980s. Overall, prescriptions have soared 400 percent since that time. The antidepressant industry tops $11 billion annually. Is it possible that these medications actually have little to no effect in most cases?

On the February 19, 2012 episode of 60 Minutes, Lesley Stahl reported on a recent study that suggests that the benefits of the newer antidepressant medications can best be explained as resulting from the placebo effect. Harvard psychologist Irving Kirsch’s meta-analysis of published and unpublished FDA drug trials show that the difference in effect between the drugs and placebo is not clinically significant.

The placebo effect occurs when a patient takes a dummy pill with no medication in it, or receives a bogus treatment, and symptoms subside due to the patient’s expectation of healing. “The difference between the effect of a placebo and the effect of an antidepressant is minimal for most people,” Kirsch stated on 60 Minutes.

Kirsch’s findings pertain to mild to moderate depression only, which is much more common than the more serious condition of major depressive disorder. “The only place where you get a clinically meaningful difference is at these very extreme levels of depression,” he stated.

While most experts agree that antidepressants work well for the severely depressed, whether they work for moderate depression has been debated since the 1990s, shortly after SSRIs became available. Kirsch’s findings were in the news last year and consumer groups have become increasingly vocal about the drawbacks of using any psychiatric medication.

Most recently, The National Coalition for Mental Health Recovery (NCMHR), a coalition made up of 32 statewide organizations of individuals in recovery from mental health conditions, issued a press release on May 3, 2012 indicating its support of the Occupy the APA (American Psychiatric Association) protest on May 5th,, 2012.

Occupy the APA was a peaceful protest of the Diagnostic and Statistical Manual of Mental Disorders (DSM), “the controversial ‘bible’ of the APA.” NCMHR opposes the substantial expansion of psychiatric labels in the new DSM and holds that “psychiatric labeling is a pseudoscientific practice of limited value in helping people recover.”

The Coalition believes that the roots of mental illness and much human suffering are socioeconomic and political. The effects of trauma in people’s lives also play a central role. The group advocates moving away from the medical model of psychiatry, and medications, to a peer led, trauma-informed and recovery-based approach.

The medical community is divided by Kirsch’s study and its implications for the treatment of depression. Stahl interviewed Dr. Walter Brown, a clinical professor of psychiatry at Brown University’s Medical School. He has co-authored two studies that corroborate Kirsch’s findings. Brown also pointed out that Kirsch “questions the widely held theory that depression is caused by a deficiency in the brain chemical called serotonin.” Most antidepressants target serotonin.

She also talked to Dr. Michael Thase, a professor of psychiatry at the University of Pennsylvania School of Medicine. Thase maintains that in practice the benefits to individual patients justify the use of the meds for the moderately depressed. He estimates SSRIs are useful for 14% of moderately depressed patients, over and above the placebo. Given that depression is so prevalent, this amounts to benefits for hundreds of thousands of people, a significant advantage in treatment.

The April 2012 Psychiatric Times responded to the 60 Minutes report by citing a February 2012 study in Germany that showed psych meds to be as effective as other medications used in general medicine. This meta-analysis measured “effect sizes” of psychiatric medications and general medicine meds. Effect size is a measure to compare the relative effectiveness of different kinds of treatments.

An effect size of 0.2 is considered significant but low, while an effect size of 0.8 is considered high. Among the findings, antidepressants used as maintenance treatment for major depression showed an effect size of 0.64, well within the range of significant effect.

Peter Kramer, psychiatrist and author of the 2005 book Against Depression, made this point in his July 9, 2011 New York Times Sunday Review article, “In Defense of Antidepressants”. He wrote, “Antidepressants work – ordinarily well, on a par with other medications doctors prescribe.”

Kirsch initially went public with his findings in the 2010 book The Emperor’s New Drugs: Exploding the Antidepressant Myth. Marcia Angell, former editor in chief of the New England Journal of Medicine, favorably reviewed the book in the June 23 and July 14, 2011 New York Review of Books.

In her review of three recent provocative books on psychiatry, she raised numerous questions about the current practices of psychiatry regarding the use of medication.

To begin, she notes that none of the three authors reviewed subscribes to the “chemical imbalance” theory of mental illness.

That theory holds that an imbalance in the chemical neurotransmitters in the brain causes mental illness. Psychiatric medications, thus, function to restore the natural balance of the chemicals in the brain.

In depression that imbalance is attributed to low levels of the neurotransmitter serotonin. Because some antidepressants raise levels of serotonin in the brain, it was postulated that depression is caused by a depletion of serotonin.

“But the main problem with the theory is that after decades of trying to prove it, researchers have still come up empty-handed,” according to Angell and the three authors she reviewed. Because the treatment of depression with psychiatric drugs is based on the chemical imbalance theory, it seems then that such treatment has no scientific justification.

In the 60 Minutes segment Dr. Brown noted that the “experts in the field now believe that that theory (serotonin imbalance) is a gross oversimplification and probably is not correct.” But in the April 22, 2012 New York Times Magazine, Dr. Siddhartha Mukherjee takes a closer look at the role of serotonin in depression.

He describes a model for depression that includes a prominent role for serotonin, but not in the way scientists and the general public have come to think about it. In his review of the latest research, Mukherjee discovered that depression might be linked to the death of neurons in the brain. In addition, some antidepressants have been shown to stimulate the growth of new brain neurons.

This research suggests that the medications “may transiently increase serotonin in the brain, but their effect is seen only when new neurons are born,” writes Mukherjee. The chemical theory of depression then moves from static to dynamic – antidepressants may actually change the wiring of the brain, rather than simply boost the levels of serotonin.

Mukherjee concludes by noting that scientific breakthroughs are most often preceded by technological invention. In this case, the SSRIs have paved the way for a better understanding of depression by focusing attention on serotonin. He states, “Our current antidepressants are thus best conceived not as medical breakthroughs but as technological breakthroughs” and give us an early glimpse into our brains and depression.

Responding to Angell’s article, Kramer challenges the strength of Kirsch’s findings. He points out that the FDA studies on which Kirsch based his analysis are not suited to answer questions about mild depression.

Because drug companies have had an incentive from the FDA to run quick, sloppy trials, the recruitment process for drug trials may have led to an exaggerated finding of placebo responses. He notes that placebo responses have risen in recent years, with up to 40 percent of subjects not receiving medication getting better in some trials.

He argues that “antidepressants appear to have effects across the depressive spectrum.” Kramer concludes that “the result that the debunking analyses propose remains implausible: antidepressants help in severe depression, depressive subtypes, chronic minor depression, social unease and a range of conditions modeled in mice and monkeys – but uniquely not in isolated episodes of mild depression in humans.”

Besides a split in the medical community, users and opponents of psychiatric drugs have diametrically opposed views on what Kirsch’s findings mean for everyday people.

The Consumer Movement, made up of users and former users of psychiatric services, is split about the medication issue, according to Amy Smith, a Denver mental health advocate. “It looks to me that the movement has become very, very polarized in the last few years,” she said. Smith agreed with the Kirsch findings, as part of a larger belief that psych meds are not the only, or best, way to treat mental health conditions.

Smith calls herself a psychiatric “survivor”, having used psych meds most of her adult life. In 2007, she weaned herself off all of her meds and severed her relationship to the psychiatric system. “In some ways it’s like waking up from a nightmare,” she explains. She now relates and connects to other people better and remembers her dreams, after twenty years without them. “I can think clearly and I can process information, I can make assessments and self-assess on how I’m doing,” she said.

Going med-free has its challenges as well, however. Because of her choice, Smith feels she has been unfairly excluded from the Colorado mental health policy community, previously her biggest support system. “My community is the mental health community and they don’t want me anymore.”

Coping without the medication is also difficult. “It’s hard. It’s really hard to do this, especially if you’ve been medicated for a long time.” In fact she says, “Yes! I was much more comfortable on psych drugs. Absolutely.”

But she didn’t realize how much the meds were impacting her life and thinking until she got off them. “One of the first things that psych drugs do to a person, any kind of psych drug, is remove your ability to self-assess who you are and how you’re thinking and how you’re relating.”

“I have to work really hard all the time to maintain my good mental health, but to me it’s worth it.”

The core belief underlying Smith’s perspective on medication is that her troubling experiences are not a biological illness. “I don’t think it’s an illness. I absolutely know that I experience life differently than many other people do.” She attributes this difference to a particularly traumatic childhood.

“It’s a different way of thinking. It’s a different way of relating,” she explained. Smith points out that “this is a society that doesn’t want people behaving differently.”

John Wotkyns, a psychologist in Seattle, Washington, echoes Smith’s concerns. He cites systemic and cultural reasons for the experience of mental illness. Rather than treating with medication, he suggests a broad social treatment is the best course of action. This would include community exercise, such as a running or walking group, and cultivating meaningful relationships with family and friends for social support.

Meanwhile, Ann Lokey, an entrepreneur in Seattle, swears by her antidepressant medication. “It just changed my life…I think they should put it in the water.” Lokey relates how her meds alleviated the extreme irritability she experienced from her depression. Now, “nothing bothers me. I’m able to forgive anybody for anything. I call it religion in a pill,” she says.

She noticed a change in her thinking patterns when she started taking Paxil over a decade ago. “It allowed a part of my personality, my compassionate side and my…capability to connect to people, it allowed those qualities to come forward in a very meaningful way,” she explained.

However, Lokey reports some negative side effects. She feels her mind has slowed down a bit and the medication “slows down my reaction…relative to what I had been,” she said. She has also experienced substantial weight gain and loss of libido, common reactions to antidepressants. Many people refuse meds based solely on these two side effects.

Because of the quality of life she enjoys while taking meds, Lokey is non-plussed by the side effects. She also feels that she could not have achieved the same wellness through psychotherapy alone. “No amount of talk therapy ever resolved the issues that the medications resolved for me. None, not even close,” she reports.

She is not swayed by Kirsch’s research, although she had heard about it. “I don’t believe it. I’m sorry, it just has not been my experience. It’s really hard to believe that that’s (the placebo effect) what’s going on for me.” She believes that as researchers look further into the issue, there will be new findings that support the use of antidepressants. “I don’t doubt that they had research. I don’t doubt that they had findings, but I suspect that there will be more,” she maintains.

It is ironic that Lokey reports feeling a little slowed by her meds but accepts it as the cost for an overall better quality of life. Smith, on the other hand, rejoices at the mental clarity she regained by getting off meds and accepts social and emotional discomfort as the trade-off.

Neither Smith nor Lokey changed her view about the use or effectiveness of antidepressants, or medication generally. Yet a great concern over Kirsch’s report is that it will encourage people already taking antidepressants to stop without their doctor’s approval. It can be very difficult to withdraw from these medications and they should not be discontinued abruptly. Others who need medication treatment may be reluctant to try it.

John Davis, MD, a co-author of the German study on effect size, warns against trivializing the efficacy of psych meds in the media because it can have deadly consequences. He reports that some patients he knows who quit their medications ended up back in the hospital, and some eventually committed suicide after going off.

Davis adds that the study is especially important for primary care physicians and other physicians who may not believe in the efficacy of psychiatric medications. By not prescribing the meds and/or discouraging patients from using them, such doctors risk great harm to their patients.

Kramer states the point more emphatically: “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.”

While the evidence from the psychiatric establishment clearly favors the continued use of antidepressants, critics are wary of the relationship between psychiatry and the pharmaceutical industry.

Angell notes that her three authors also agree on “the disturbing extent to which the companies that sell psychoactive drugs – through various forms of marketing, both legal and illegal, and what many people would describe as bribery – have come to determine what constitutes a mental illness and how the disorders should be diagnosed and treated.”

In particular, she criticizes the DSM for lacking citations to scientific studies to support its findings. Because the boundaries between normal and abnormal in psychiatry are often unclear, psychiatrists are able “to expand diagnostic boundaries or even create new diagnoses, in ways that would be impossible, say, in a field like cardiology,” Angell asserts.

“And drug companies have every interest in inducing psychiatrists to do just that,” she concludes.

In the end, the choice to take or not take antidepressants, or any psych drug, is a very personal one. If you’re new to the discussion, it can be very confusing. The best course is to consider the evidence on both sides and re-evaluate regularly as new information becomes available.

While the SSRIs may not be the wonder drugs we were promised, they work well in a wide range of applications beyond mild to moderate depression. The thinking they have inspired about serotonin may bring the medical breakthrough required to defeat depression, and put the debate over how to treat it to rest.







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About Brian Binford

Brian Binford is a freelance writer, attorney and advocate for people with disabilities. He specializes in school and employment issues for people with bipolar disorder and depression. He lives in Denver, Colorado.

One Response to “Antidepressants and Placebo: Voices Split on Effectiveness”

  1. On May 26, 2012 at 9:45 AM Fred responded with... #

    Agreed this is the most important topic of the three.

    Just from reading the article it seems pretty clear that in the case of major depressive catagories the medications make a significant contribution. I guess you are suggestiing the other catagories are errors or unjustified extentions of the diagnosiis and do not really represent depressive conditions requiring chemical intervention.
    I think that is consistent with the way society has moved in the direction of trying to give everyone a diagnosis if they behave outside the norm.
    Maybe KISS is an appropriate description of what should be done to the DSM.

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