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The challenge of going off psychiatric drugs

bipolarMillions of Americans have taken antidepressants for many years. What happens when it’s time to stop? asks Rachel Aviv in The New Yorker.

This long, fascinating and impeccably researched article can be read in full on The New Yorkersite, linked to below. It tells the story of Laura Delani, a wealthy young American and Harvard graduate, and her long struggle with mental health issues via antidepressants and other medications that did not help her sufficiently and were difficult to quit.

This excerpt focuses on a small section of the article that investigates the use of drugs for mental illnesses, research and developments in the field, and the very many challenges facing the use of drugs to treat chemical imbalances and withdrawal from them…

Genetics plays a role in mental disorder, as do environmental influences, but the drugs prescribed do not have the specificity to target the causes of an illness.

Wayne Goodman, a former chair of the FDA’s Psychopharmacologic Drugs Advisory Committee, has called the idea that pills fix chemical imbalances a “useful metaphor” that he would never use with his patients.

Ronald Pies, a former editor of Psychiatric Times, has said, “My impression is that most psychiatrists who use this expression” – that the pills fix chemical imbalances – “feel uncomfortable and a little embarrassed when they do so. It’s kind of a bumper-sticker phrase that saves time.”

Dorian Deshauer, a psychiatrist and historian at the University of Toronto, has written that the chemical-imbalance theory, popularised in the eighties and nineties, “created the perception that the long term, even lifelong use of psychiatric drugs made sense as a logical step.” But psychiatric drugs are brought to market in clinical trials that typically last less than twelve weeks. Few studies follow patients who take the medications for more than a year.

Allen Frances, an emeritus professor of psychiatry at Duke, who chaired the task force for the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders or DSM, in 1994, told me that the field has neglected questions about how to take patients off drugs – a practice known as “de-prescribing”. He said that “de-prescribing requires a great deal more skill, time, commitment and knowledge of the patient than prescribing does.”

He emphasises what he called a “cruel paradox: there’s a large population on the severe end of the spectrum who really need the medicine” and either don’t have access to treatment or avoid it because it is stigmatised in their community. At the same time, many others are “being overprescribed and then stay on the medications for years.”

There are almost no studies on how or when to go off psychiatric medications, a situation that has created what he calls a “national public-health experiment”.

Roland Kuhn, a Swiss psychiatrist credited with discovering one of the first antidepressants, imipramine, in 1956, later warned that many doctors would be incapable of using antidepressants properly, “because they largely or entirely neglect the patient’s own experiences”.

The drugs could only work, he wrote, if a doctor is “fully aware of the fact that he is not dealing with a self-contained, rigid object, but with an individual who is involved in constant movement and change.”

Randomised clinical studies

A decade after the invention of antidepressants, randomised clinical studies emerged as the most trusted form of medical knowledge, supplanting the authority of individual case studies. By necessity, clinical studies cannot capture fluctuations in mood that may be meaningful to the patient but do not fit into the study’s categories.

This methodology has led to a far more reliable body of evidence, but it also subtly changed our conception of mental health, which has become synonymous with the absence of symptoms, rather than with a return to a patient’s baseline of functioning, her mood or personality before and between episodes of illness.

“Once you abandon the idea of the personal baseline, it becomes possible to think of emotional suffering as relapse – instead of something to be expected from an individual’s way of being in the world,” Deshauer told me.

For adolescents who go on medications when they are still trying to define themselves, they may never know if they have a baseline, or what it is. “It’s not so much a question of Does the technology deliver?” Deshauer said. “It’s a question of What are we asking of it?”

Common use of antidepressants

Antidepressants are now taken by roughly one in eight adults and adolescents in the US, and a quarter of them have been doing so for more than ten years. Industry money often determines the questions posed by pharmacological studies, and research about stopping drugs has never been a priority.

Barbiturates, a class of sedatives that helped hundreds of thousands of people to feel calmer, were among the first popular psychiatric drugs. Although leading medical journals asserted that barbiturate addiction was rare, within a few years it was evident that people withdrawing from barbiturates could become more anxious than they were before they began taking the drugs. (They could also hallucinate, have convulsions, and even die.)

Valium and other benzodiazepines were introduced in the early sixties, as a safer option. By the seventies, one in ten Americans was taking Valium. The chief of clinical pharmacology at Massachusetts General Hospital declared, in 1976, “I have never seen a case of benzodiazepine dependence” and described it as “an astonishingly unusual event.” Later, though, the F.D.A. acknowledged that people can become dependent on benzodiazepines, experiencing intense agitation when they stop taking them.

Selective serotonin reuptake inhibitors

Selective serotonin reuptake inhibitors, or SSRIs – most prominently Prozac and Zoloft – were developed in the late eighties and early nineties, filling a gap in the market opened by scepticism toward benzodiazepines.

SSRIs were soon prescribed not just for depression but for the nervous ailments that the benzodiazepines had previously addressed. (There had been other drugs used as antidepressants, but they had often been prescribed cautiously, because of concerns about their side effects.)

As Jonathan Metzl writes, in “Prozac on the Couch”, SSRIs were marketed especially to female consumers, as drugs that would empower them at work while preserving the kind of feminine traits required at home.

One advertisement for Zoloft showed a woman in a pants suit, holding the hands of her two children, her wedding ring prominent, next to the phrase “Power That Speaks Softly.” Today, antidepressants are taken by one in five white American women.

Concerns about withdrawal symptoms emerged shortly after SSRIs came to market, and often involved pregnant women who had been told to discontinue their medications, out of concern that the drugs could affect the fetus.

A 2001 article in the Journal of Psychiatry & Neuroscience chronicled thirty-six women who were on either antidepressants, benzodiazepines, or a combination of the two, and who stopped taking the drugs when they became pregnant. A third of the patients said they felt suicidal, and four were admitted to a hospital. One had an abortion, because she no longer felt capable of going through with the pregnancy.

Internal records of pharmaceutical manufacturers show that the companies have been aware of the withdrawal problem.

At a panel discussion in 1996, Eli Lilly invited seven experts to develop a definition of antidepressant withdrawal. Their findings were published in a supplement of the Journal of Clinical Psychiatry that was sponsored by Eli Lilly and was highly favorable to the company’s own product, Prozac, which has the longest half-life of all the SSRIs; the drug clears slowly from the body.

The panelists observed that withdrawing from other antidepressants was more likely to lead to “discontinuation reactions,” such as agitation, detachment, “uncharacteristic crying spells and paralyzing sadness”.

“Although generally mild and short-lived,” one paper in the supplement explained, “discontinuation symptoms can be severe and chronic.” The panel defined “discontinuation syndrome” as a condition that could be “rapidly reversed by the reintroduction of the original medication.”

Shortly after the Eli Lilly panel, SmithKline Beecham, which manufactured Paxil, distributed a memo to its sales team accusing Eli Lilly of “trying to hide” the withdrawal symptoms of its products. “The truth of the matter is that the only discontinuation syndrome Lilly is worried about is the discontinuation of Prozac,” the memo said. In another internal memo, SmithKline Beecham instructed staff to “highlight the benign nature of discontinuation symptoms, rather than quibble about their incidence.”


Guy Chouinard, a retired professor of psychiatry at McGill and at the University of Montreal, who served as a consultant for Eli Lilly for ten years and did one of the first clinical trials of Prozac, told me that when SSRIs came on the market he was thrilled to see his patients, previously crippled by self-doubt and fear, living tolerable and fulfilling lives.

Chouinard is considered one of the founders of psychopharmacology in Canada. In the early 2000s, he began to see patients who, after taking certain antidepressants for years, had stopped their medications and were experiencing what he described as “crescendo-like” anxiety and panic that went on for weeks and, in some cases, months. When he reinstated their medication, their symptoms began to resolve, usually within two days.

Most people who discontinue antidepressants do not suffer from withdrawal symptoms that last longer than a few days. Some experience none at all. “The medical literature on this is a mess,” Chouinard told me. “Psychiatrists don’t know their patients well – they aren’t following them long-term – so they don’t know whether to believe their patients when they say, ‘I’ve never had this experience in my life.’”

He thinks that withdrawal symptoms, misdiagnosed and never given time to resolve, create a false sense that patients can’t function unless they go back on their drugs.

Giovanni Fava, a professor of psychiatry at the University of Buffalo, has devoted much of his career to studying withdrawal and has followed patients suffering from withdrawal symptoms a year after stopping antidepressants.

A paper published last month in a journal he edits, Psychotherapy and Psychosomatics, reviewed eighty studies and found that in nearly two-thirds of them patients were taken off their medications in less than two weeks. Most of the studies did not consider how such an abrupt withdrawal might compromise the studies’ findings: withdrawal symptoms can easily be misclassified as relapse.

Fava’s work is widely cited, yet he said that he has struggled to publish his research on this topic. To some degree, that makes sense: no one wants to deter people from taking drugs that may save their life or lift them out of disability.

But to avoid investigating or sharing information on the subject – to assume that people can comprehend the drugs’ benefits and not their limits – seems to repeat a pattern of paternalism reminiscent of earlier epochs in the history of psychopharmacology.

David Taylor, the director of pharmacy and pathology at the Maudsley Hospital, in London, and the author of more than three hundred peer-reviewed papers, told me: “It is not as though we haven’t been burned by this before.” If he hadn’t experienced antidepressant withdrawal himself, Taylor said, “I think I would be sold on the standard texts.” But, he said, “experience is very different from what’s on the page.”

Taylor described his own symptoms of withdrawal, from the antidepressant Effexor, as a “strange and frightening and torturous” experience that lasted six weeks. In a paper published in March in Lancet Psychiatry, he and a co-author reviewed brain imaging and case studies on withdrawal and argued that patients should taper off antidepressants over the course of months, rather than two to four weeks, as current guidelines advise.

Such guidelines are based on a faulty assumption that, if a dose is reduced by half, it will simply reduce the effect in the brain by half. The paper asserts that the increasing long-term use of antidepressants “has arisen in part because patients are unwilling to stop due to the aversive nature of the withdrawal syndrome.”

But, Taylor told me, his research “wouldn’t stop me from recommending an antidepressant for someone with fully fledged major depression, because the relief of suffering is of a different order of magnitude than the symptoms when you stop taking them.”

In the fifth edition of the DSM, published in 2013, the editors added an entry for “antidepressant discontinuation syndrome” – a condition also mentioned on drug labels – but the description is vague and speculative, noting that “longitudinal studies are lacking” and that little is known about the course of the syndrome. “Symptoms appear to abate over time,” the manual explains, while noting that “some individuals may prefer to resume medication indefinitely.”

The article goes on to describe the dearth of medical assistance with the process of withdrawa and a range of initiatives – such as forums and online communities and guidelines – that have been developed to tackle the problem. One of them is Laura’s website, called the Withdrawal Project, which was launched last year and is devoted to helping people make more informed choices about psychiatric treatment.

*This article appears in the print edition of the 8 April 2019 issue, with the headline “Bitter Pill.”

[link url=""]The Challenge of Going Off Psychiatric Drugs[/link]

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