Many People Taking Antidepressants Discover They Cannot Quit
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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 Ms. Toline, 27, of Tacoma, Wash. 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.”
Nearly
25 million adults, like Ms. 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 drug makers or government regulators, who felt antidepressants could not be addictive and did far more good than harm.
The
drugs initially were approved for short-term use, following 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 over the past decade in Britain, where health officials in January began a nationwide review of prescription drug dependence and withdrawal.
In New Zealand, where prescriptions are also at historic highs, a survey of long-term users
found that withdrawal was the most common complaint, cited by three-quarters of long-term users.
Yet
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.
With
government funding, he is developing online and telephone support to
help practitioners
and patients. “Should we really be putting so many people on antidepressants long-term when we don’t know if it’s good for them, or whether they’ll be able to come off?” he said.
Later studies suggested that “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, physicians in the United States 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.
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. 
“But
the patient and doctor don’t know this and give the antidepressant
credit it doesn’t deserve.
Both are reluctant to stop what appears to be a winner, and the useless prescription may be continued for years — or a lifetime.”
The
Times analyzed data gathered since 1999 as part of the National Health
and Nutrition Examination Survey. Over all, more than 34.4 million
adults took antidepressants in 2013-4,
up from 13.4 million in the 1999-2000 survey.
Adults
over 45, women and whites are more likely to take antidepressants than
younger adults,
men and minorities. But usage is increasing in older adults across the demographic spectrum.  
“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.
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.
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 paresthesia
— 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 antide-
pressant Paxil 21 years ago for severe premenstrual syndrome
on the recommendation of her gynecologist.
“He said, ‘Oh, this little pill is going to change your life,’ ” Ms. Hempel said. “Well, did it ever.”
The
drug blunted her PMS symptoms, she said, but also caused her to gain 40
pounds in nine
months. Quitting was nearly impossible — at first, her
doctor tapered her too quickly, she said.
She
succeeded in her last attempt, in 2015, by tapering over months to 10
milligrams, then five,
down from 20 milligrams and “finally all the way
down to particles of dust,” after which she
was bedridden for three
weeks with severe dizziness, nausea and crying spells, she said.
“Had
I been told the risks of trying to come off this drug, I never would
have started it,” Ms.
Hempel said. “A year and a half after stopping,
I’m still having problems. I’m not me right now;
I don’t have the
creativity, the energy. She — Robin — is gone.”
At least some of the most pressing questions about antidepressant withdrawal will soon have an answer.
Dr. Mangin, of McMaster University, led a research team in New Zealand that recently
completed the first rigorous, long-term trial of withdrawal.
The
team recruited more than 250 people in three cities who had been taking
Prozac long-term
and were interested in tapering off. Two-thirds of the
group had been on the drug for more than
two years, and a third for
more than five years.
The
team randomly assigned the participants to one of two regimens. Half
tapered slowly,
receiving a capsule each day that, over a period of a
month or longer, contained progressively
lower amounts of the active
drug.
The
other half believed they were tapering but got capsules that in fact
maintained their regular dosage. The researchers followed both groups
for a year and a half. They are still working
through the data, and
their findings will be published in the coming months.
But
one thing is already clear from this effort and other clinical
experience, Dr. Mangin said:
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.
For
now, people who haven’t been able to quit just by following a doctor’s
advice are turning
to a method called microtapering: making tiny
reductions over a long period of time, nine
months, a year, two years —
whatever it takes.
“The
tapering rates given by doctors are often way, way too fast,” said
Laura Delano, who had
severe symptoms while trying to get off several
psychiatric drugs. She has created a website,
The Withdrawal Project, that provides resources on psychiatric drug withdrawal, including a
guide to tapering off.
She
is hardly the only one bewildered by the scarcity of good medical
advice about unwinding prescriptions that have become so common.
“It
has taken a long, long time to get anyone to pay attention to this
issue and take it seriously,”
said Luke Montagu, a media entrepreneur
and co-founder of the London-based Council for Evidence-Based
Psychiatry, which pushed for Britain’s review of prescription drug
addiction
and dependence.
“You’ve
got this huge parallel community that’s emerged, largely online, in
which people are supporting each other though withdrawal and developing
best practices largely without the help
of doctors,” he said.
Dr.
Stockmann, the psychiatrist in East London, wasn’t entirely convinced
withdrawal was a
serious issue before he went through it himself. His
microtapering strategy finally worked.
“There
was a really significant moment,” he recalled. “I was walking down near
my house,
past a forest, and I suddenly realized I could feel the full
range of emotions again. The birds
were louder, the colors more vivid — I
was happy.”
“I
have seen lots of people — patients — not being believed, not taken
seriously when they complained about this,” he added. “That has to
stop.”
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