“What you see is the number of long-term users just piling up year after year,” said Dr. Dr. Mark Olfson, a professor of psychiatry at Columbia University. Dr. Olfson and Dr. Ramin Mojtabai, a professor of psychiatry at Johns Hopkins University, assisted The Times with the analysis.
Still, it is not at all 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.
Dr. Peter Kramer, a psychiatrist and author of several books about antidepressants, said that while he generally works to wean patients with mild-to-moderate depression off medication, some report that they do better on it.
“There is a cultural question here, which is how much depression should people have to live with when we have these treatments that give so many a better quality of life,” Dr. Kramer said. “I don’t think that’s a question that should be decided in advance.”
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 that is hard to measure: Daily pill-popping leaves them doubting their own resilience, they say.
“We’ve come to a place, at least in the West, where it seems every other person is depressed and on medication,” said Edward Shorter, a historian of psychiatry at the University of Toronto. “You do have to wonder what that says about our culture.”
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.
In another study of 180 longtime antidepressant users, withdrawal symptoms were reported by more than 130. Almost half said they felt addicted to antidepressants.
“Many were critical of the lack of information given by prescribers with regard to withdrawal,” the authors concluded. “And many also expressed disappointment or frustration with the lack of support available in managing withdrawal.”
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.
Nausea and ‘Brain Zaps’
As far back as the mid-1990s, leading psychiatrists recognized withdrawal as a potential problem for patients taking modern antidepressants.
At a 1997 conference in Phoenix sponsored by drug maker Eli Lilly, a panel of academic psychiatrists produced a lengthy report detailing the symptoms, like balance problems, insomnia and anxiety, that went away when the pills were restarted.
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But soon the topic faded from the scientific literature. And government regulators did not focus on these symptoms, seeing rampant depression as the larger problem.
“What we were concentrating on was recurrent depression,” said Dr. Robert Temple, deputy director for clinical science in the F.D.A.’s Center for Drug Evaluation and Research. “If people’s heads went through the roof from withdrawal, I think we would have seen it.”
Drug makers had little incentive to mount costly studies of how best to quit their products, and federal funding has not filled the research gap.
As a result, the drugs’ labels, on which doctors and many patients rely, provide very little guidance for ending a prescription safely.
“The following adverse events were reported at an incidence of 1 percent or greater,” reads the label for Cymbalta, a leading antidepressant. It lists headaches, fatigue and insomnia, among other reactions in patients trying to stop.
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.
In a study of Cymbalta, another Eli Lilly drug, people in withdrawal experienced two to three symptoms on average. The most common were dizziness, nausea, headache and “parathesia” — electric-shock sensations in the brain that many people call brain zaps. Most of these symptoms lasted longer than two weeks.
“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.”
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,” Dr. Stockmann said, “but I had no idea how hard it would be.”
Robin Hempel, 54, a mother of four who lives near Concord, N.H., began taking the antidepressant Paxil 21 years ago for severe premenstrual syndrome on the recommendation of her gynecologist.
Source : Nytimes
