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Antidepressants on trial: Are they a wonder or a danger?

Argument rages over the benefits and risks of Prozac and other SSRIs. New books from a psychiatrist and a former patient give the cases for and against

By Robert Whitaker

6 July 2016

Prozac

Prozac was touted as a wonder drug, making us “better than well”

Carolina Miranda/Getty

THE ongoing controversy about the merits of antidepressants might be best described as a battle of narratives. The psychiatric profession tells of drugs that have a history of proven efficacy. The critics tell of drugs that have marginal short-term efficacy, may do more harm than good in the long term, and, on occasion, may cause a person to seriously deteriorate. Both claim science’s mantle, which leaves the public uncertain what to think.

Two new books, one by American psychiatrist Peter Kramer and the other by British film-maker Katinka Blackford Newman, illustrate aspects of these competing narratives.

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Kramer helped fuel the boom in a class of antidepressants – SSRIs – with his 1993 book Listening to Prozac, which told of a drug that could make even people without depression “better than well”. Prozac and other SSRIs were touted in the media as “wonder drugs”, and while the “wonder” has long since dimmed, use of antidepressants in most developed countries has climbed steadily.

“Many people in the drug trials, Kramer argues, were not really depressed but enrolled to get paid“

It was mounting criticism of the drugs that piqued Kramer’s interest. In particular, there was the work of psychologist Irving Kirsch, who had concluded from his own meta-analysis of data submitted to the US Food and Drug Administration that antidepressants provide no clinically meaningful benefit over placebo for people with mild to moderate depression. This prompted Kramer to write Ordinarily Well: The Case for Antidepressants. “I was ready to engage,” he explains.

Kramer, it’s fair to say, still sees antidepressants through a rose-coloured lens. If his description of them reflects a clinical reality, they deserve to be called wonder drugs. In primary care, he writes, 90 per cent of patients respond well to an antidepressant. Even those with chronic symptoms, “if they hang in, will achieve remission”, he says. The drugs work in a diverse group of people, including those who are only mildly depressed, and can give dour people new personalities, making them more cheerful and less ruminative.

According to Kramer, their side effects are fewer than we might think, they dramatically reduce the risk of recurrent depressive episodes, and even if they aren’t a cure, the person still functions fairly well. He says that antidepressants “restore resilience” to mind and brain, and “confer overall well-being”.

As for Kirsch’s research, Kramer believes the conclusion antidepressants provide little benefit over placebo is “implausible”. For him, the fact the UK’s National Institute for Health and Care Excellence recommends non-pharmacological therapies as first-line treatments for mild to moderate depression is an example of how “evidence-based medicine” can lead the medical profession astray.

Many of the people in the SSRI trials, Kramer argues, were not really depressed but enrolled to get paid. The attention lavished on them in studies produced an inflated response for the placebo group. At the same time, he says, the Hamilton scale that measures outcomes doesn’t capture the many aspects of well-being antidepressants promote. This suppressed response rates for the medicated group, says Kramer. Psychiatrists, he writes, “are aware that the Pharma trials are shameful, ethically and scientifically”.

It might have been nice for American psychiatry to confess this 25 years ago, when Prozac and the other SSRIs were hailed as breakthrough medications. But Kramer’s dismissal of the trials provides a good segue into the counter-narrative perspective, which, I must confess, I share.

No panacea

The usual thought is that big pharma design trials to favour their drugs and suppress the placebo response. One way they do so is to exclude those with co-morbidities and suicidal tendencies, which leads to a selection of participants most likely to respond well to the medication.

But this raises an obvious question: how effective are antidepressants in regular clinical practice? More than a decade ago, the US’s National Institute of Mental Health set out to answer that, and the results were dismal: only 26 per cent of patients even responded to an antidepressant, and at the end of a year, only 6 per cent were well. These findings “reveal remarkably low response and remission rates,” the investigators concluded.

Such is one of many counter-arguments that could be made to Kramer. Even more troubling, there are many studies telling of a significant percentage of those treated with antidepressants who become chronically ill. It is also notable that in countries with widespread antidepressant use, the number of adults living on disability benefits due to mood disorders has soared. At least from a societal perspective, these drugs have not proven to be a panacea.

As for the voices of those being treated, although Kramer relates numerous anecdotes of people getting well under his care, we never hear directly from them. In fact, many of the stories are “composites”, which is to say, they are not real. Kramer is describing how he sees his patients and not how people see themselves, which may be very different.

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In her memoir The Pill That Steals Lives, Katinka Blackford Newman tells a story that rarely makes it into the conventional narrative. Struggling while going through a divorce, Newman, a documentary film-maker who had worked for the BBC, went to see a psychiatrist, who prescribed escitalopram (Lexapro). Once on the drug, she became severely anxious and restless, which are symptoms of akathisia, a side effect associated with violence and suicide.

Thoughts of committing such acts crept into her head and soon grew into a full-blown delusion that she had killed her two children. She was hospitalised, and thus began her downward spiral into a life on antipsychotics and other psychiatric drugs, including Prozac. Before long, she had lost the capacity to care for herself and her children. A horrible year passed, and it was only after she withdrew from most of her medications that her long path to recovery began. “It really was like waking up out of a coma,” she writes.

Newman tells of a number of people who committed inexplicable acts of violence after going on an antidepressant, and details how such extreme adverse reactions show up in research.

While such stories may come from the far end of the spectrum of experiences, they provide an important counter to the conventional narrative. As such, they prompt society to think of the many disparate effects that antidepressants can have, including the possibility that they may do harm.

Ordinarily Well: The case for antidepressants

Peter D. Kramer and Farrar

Straus and Giroux

This article appeared in print under the headline “Listening to everyone”

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