Many who try to quit say they cannot because of withdrawal symptoms they were never warned about.
Victoria Toline would hunch over the kitchen table, steady her hands and draw a bead of liquid from a vial with a small dropper. It was a delicate operation that had become a daily routine — extracting ever tinier doses of the antidepressant she had taken for three years, on and off, and was desperately trying to quit.
“Basically that’s all I have been doing — dealing with the dizziness, the confusion, the fatigue, all the symptoms of withdrawal,” said Toline, 27, of Gig Harbor. It took nine months to wean herself from the drug, Zoloft, by taking increasingly smaller doses.
“I couldn’t finish my college degree,” she said. “Only now am I feeling well enough to try to re-enter society and go back to work.”
Long-term use of antidepressants is surging in the United States, according to a new analysis of federal data by The New York Times. Some 15.5 million Americans have been taking the medications for at least five years. The rate has almost doubled since 2010, and more than tripled since 2000.
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Nearly 25 million adults, like Toline, have been on antidepressants for at least two years, a 60 percent increase since 2010.
The drugs have helped millions of people ease depression and anxiety, and are widely regarded as milestones in psychiatric treatment. Many, perhaps most, people stop the medications without significant trouble. But the rise in longtime use is also the result of an unanticipated and growing problem: Many who try to quit say they cannot because of withdrawal symptoms they were never warned about.
Some scientists long ago anticipated that a few patients might experience withdrawal symptoms if they tried to stop; they called it “discontinuation syndrome.” Yet withdrawal has never been a focus of drugmakers or government regulators, who believed antidepressants could not be addictive and did far more good than harm.
The drugs initially were approved for short-term use, after studies typically lasting about two months. Even today, there is little data about their effects on people taking them for years, although there are now millions of such users.
Expanding use of antidepressants is not just an issue in the United States. Across much of the developed world, long-term prescriptions are on the rise. Prescription rates have doubled in the past decade in Britain, where health officials in January began a nationwide review of prescription-drug dependence and withdrawal.
The medical profession has no good answer for people struggling to stop taking the drugs — no scientifically backed guidelines, no means to determine who’s at highest risk, no way to tailor appropriate strategies to individuals.
“Some people are essentially being parked on these drugs for convenience’s sake because it’s difficult to tackle the issue of taking them off,” said Dr. Anthony Kendrick, a professor of primary care at the University of Southampton in Britain.
Antidepressants were originally considered a short-term treatment for episodic mood problems, to be taken for six to nine months: enough to get through a crisis, and no more.
Later studies suggested “maintenance therapy” — longer-term and often open-ended use — could prevent a return of depression in some patients, but those trials very rarely lasted more than two years.
Once a drug is approved, U.S. physicians have wide latitude to prescribe it as they see fit. The lack of long-term data did not prevent doctors from placing tens of millions of Americans on antidepressants indefinitely.
“Most people are put on these drugs in primary care, after a very brief visit and without clear symptoms of clinical depression,” said Dr. Allen Frances, a professor emeritus of psychiatry at Duke University. “Usually there’s improvement, and often it’s based on the passage of time or placebo effect.
“But the patient and doctor don’t know this and give the antidepressant credit it doesn’t deserve.”
Still, it is not clear that everyone on an open-ended prescription should come off it. Most doctors agree that a subset of users benefit from a lifetime prescription, but disagree over how large the group is.
The Times analyzed data gathered since 1999 as part of the National Health and Nutrition Examination Survey. Overall, more than 34.4 million adults took antidepressants in 2013-14, up from 13.4 million in the 1999-2000 survey.
“What you see is the number of long-term users just piling up year after year,” said Dr. Mark Olfson, a professor of psychiatry at Columbia University. Olfson and Dr. Ramin Mojtabai, a professor of psychiatry at Johns Hopkins University, assisted The Times with the analysis.
Antidepressants are not harmless; they commonly cause emotional numbing, sexual problems like a lack of desire or erectile dysfunction, and weight gain. Long-term users report in interviews a creeping unease: Daily pill-popping leaves them doubting their own resilience, they say.
Patients who try to stop taking the drugs often say they cannot. In a recent survey of 250 long-term users of psychiatric drugs — most commonly antidepressants — about half who wound down their prescriptions rated the withdrawal as severe. Nearly half who tried to quit could not do so because of these symptoms.
Drug manufacturers do not deny that some patients suffer harsh symptoms when trying to wean themselves from antidepressants.
“The likelihood of developing discontinuation syndrome varies by individuals, the treatment and dosage prescribed,” said Thomas Biegi, a spokesman for Pfizer, maker of antidepressants like Zoloft and Effexor. He urged that patients work with their doctors to “taper off” — to wean themselves by taking shrinking doses — and said the company could not provide specific withdrawal rates because it did not have them.
Drugmaker Eli Lilly, referring to two popular antidepressants, said in a statement the company “remains committed to Prozac and Cymbalta and their safety and benefits, which have been repeatedly affirmed by the U.S. Food and Drug Administration.” The company declined to say how common withdrawal symptoms are.
The few studies of antidepressant withdrawal that have been published suggest that it is harder to get off some medications than others. This is due to differences in the drugs’ half-life, the time it takes the body to clear the medication once the pills are stopped.
Brands with a relatively short half-life, like Effexor and Paxil, appear to cause more withdrawal symptoms more quickly than those that stay in the system longer, like Prozac.
In one of the earliest published withdrawal studies, researchers at Eli Lilly had people taking Zoloft, Paxil or Prozac stop the pills abruptly, for about a week. Half of those on Paxil experienced serious dizziness; 42 percent suffered confusion; and 39 percent, insomnia.
Among patients who stopped taking Zoloft, 38 percent had severe irritability; 29 percent experienced dizziness; and 23 percent, fatigue. The symptoms appeared soon after people were taken off the drugs and resolved once they resumed taking the pills.
Those on Prozac, by contrast, experienced no initial spike in symptoms when they stopped, but this result was not surprising. It takes Prozac several weeks to wash out of the body entirely, so one week’s interruption is not a test of withdrawal.
“The truth is that the state of the science is absolutely inadequate,” said Dr. Derelie Mangin, a professor in the department of family medicine at McMaster University in Hamilton, Ontario. “We don’t have enough information about what antidepressant withdrawal entails, so we can’t design proper tapering approaches.”
At least some of the most pressing questions about antidepressant withdrawal will soon have an answer. Mangin led a research team in New Zealand that recently completed the first rigorous, long-term trial of withdrawal. The results will be published in coming months.
But Mangin said one thing is already clear: Some people’s symptoms were so severe that they could not bear to stop taking the drug. “Even with a slow taper from a drug with a relatively long half-life, these people had significant withdrawal symptoms such that they had to restart the drug,” she said.
In interviews, dozens of people who had experienced antidepressant withdrawal recounted similar stories: The drugs often relieved mood problems, at first. After a year or so, it wasn’t clear whether the medication was having any effect.
Yet quitting was far harder, and stranger, than expected. “It took me a year to come completely off — a year,” said Dr. Tom Stockmann, 34, a psychiatrist in East London, who experienced lightheadedness, confusion, vertigo and brain zaps, when he stopped taking Cymbalta after 18 months.
To wind the prescription down safely, he began opening the capsules, removing a few beads of the drug each day in order to taper off — the only way out, he decided.
“I knew some people experienced withdrawal reactions,” Stockmann said, “but I had no idea how hard it would be.”