At first, Zoloft seemed like “manna from heaven,” says this 53-year-old woman, a teacher who lives in Watertown.
It was the summer of 1999 and, for reasons she still doesn’t fully understand, she had slipped into a “terrible slump.” Her doctor suggested Zoloft, America’s second most popular antidepressant, after Prozac. And for a while, it was great, says the woman, who does not want her name used.
But after nearly a year on the drug, she developed a twitch in her left eyelid. It may not have been related to the Zoloft, but since she was feeling fine, she decided to stop taking the drug.
And, unlike many people who quit antidepressants, she did it the right way: very slowly – cutting the dose little by little over six weeks.
Even so, she wound up with three months of withdrawal hell, or discontinuation syndrome, the term psychiatrists prefer because withdrawal suggests that antidepressant drugs are addictive (like cocaine or heroin), which they are not.
Discontinuation syndrome is not a recurrence of the original depression, though that can happen, too. It’s a brand new set of problems, in this woman’s case, bad headaches, vertigo, and dizziness. At one point during a walk, she says, “my body felt like it was tipping to one side. I had to keep lying down. It was terrible.”
Could a drug that was no longer in her system somehow be causing weird symptoms she’d never had before?
“That was the thing that got me the most creeped out,” she says. “The drug clearly is out of your body. So what was it that lasted for three months?”
What lasted so long for this teacher, and many others who stop taking antidepressant drugs, is what scientists now think of as a prolonged period of re-adjustment during which the chemistry of the brain settles into a kind of new, non-depressed normal.
To be sure, many of the millions of people worldwide who take antidepressants experience no withdrawal symptoms when they stop. But some studies suggest that one in every 10 have some symptoms and one in 20 suffer significant distress, says Dr. Jerrold Rosenbaum, chief of psychiatry at Massachusetts General Hospital.
Others, among them Dr. Andrew Leuchter, director of the division of adult psychiatry at the UCLA Medical Center, believe the actual figures are much higher.
Yet even doctors who should be on the lookout for withdrawal symptoms – such as dizziness, increased nervousness, irritability, insomnia, and a dramatic increase in vivid dreams – often aren’t paying close attention.
A 1997 study in the Journal of Clinical Psychiatry showed that 70 percent of general practitioners and, surprisingly, a third of psychiatrists don’t know that significant withdrawal symptoms can occur when people stop taking antidepressants called selective serotonin reuptake inhibitors, or SSRIs, including Prozac, Zoloft, Paxil, Luvox, Celexa, and a similar drug, Effexor. (Withdrawal syndromes can also occur with antidepressants that work differently from the SSRIs, including older drugs such as Elavil and Tofranil)
“It’s an under-recognized problem,” says Leuchter, because when people stop taking a drug and then develop new symptoms, they can’t believe it has”anything to do with the medicine because, if they’re not taking it, how can it affect them?”
But withdrawal clearly does happen, though researchers still aren’t sure why. The basic thinking is that depression is caused by a deficiency of serotonin, a key neurotransmitter in the brain. SSRIs boost serotonin by stopping its re-absorption into brain cells, thus keeping more serotonin where it’s needed, in the synapses, or gaps, between nerve cells.
As the brain adapts to increased levels of serotonin, some neuroscientists think there is a decline in either the number or sensitivity of the brain’s molecular gateways that can put serotonin to work. Then, when SSRIs are discontinued, withdrawal symptoms may occur as the nervous system, now primed for lots of serotonin, isn’t getting enough, says Dr. Alexander Bodkin, chief of clinical psychopharmacology research at McLean Hospital in Belmont.
One thing researchers are sure of is that the severity of withdrawal symptoms from SSRIs is closely correlated with how long the drug remains in the body. The longer the drug or its active metabolic breakdown products stay in the body, the less severe the withdrawal.
“The faster-clearing the drug, the worse the withdrawal,” says Dr. Michael Craig Miller, a psychiatrist who edits the Harvard Mental Health Letter.
Prozac is least likely to cause withdrawal because its metabolic breakdown products linger in the body for as long as five weeks. In fact, precisely because of this, one strategy for people who have trouble getting off other SSRIs is to switch to Prozac and then taper slowly off of that.
By contrast, Paxil, Luvox, and Celexa may trigger withdrawal because they are faster-clearing, lingering in the body for just four to five days. Zoloft lingers slightly longer. Effexor, a variant of standard SSRIs, has the shortest half-life of all, about 5 hours, which means it is highly likely to cause withdrawal symptoms.
Recent studies have bolstered the idea that faster-clearing drugs lead to worse withdrawal.
In 1998, Rosenbaum of MGH and his team studied 220 patients and found that those who abruptly stopped taking Paxil, and to a lesser extent, Zoloft, had significant withdrawal symptoms, while those who stopped taking Prozac did not. Another study published last year in the British Journal of Psychiatry found essentially the same pattern.
Yet another study, sponsored by Lilly Research Laboratories (Eli Lilly makes Prozac) and published last year in Psychoneuroendocrinology, showed that people who suddenly stopped taking Paxil had a significant increase in heart rate and stress hormone levels, while those taking Zoloft or Prozac did not.
The bottom line is that if you want to wean yourself from antidepressants, do so slowly, by decreasing your dose by half every one to two weeks. It may take weeks or even months to discontinue completely, but that doesn’t really matter.
“There’s never a rush in getting off these medications,” says Leuchter of UCLA. “What’s the hurry? If you have been on them for six to 12 months and you’re tolerating them well, there’s no point in going too quickly.”
And if you do develop withdrawal symptoms despite tapering off slowly, try going back to the previous dose, then switching to Prozac and weaning yourself from that.
The most important lesson, says the teacher from Watertown, who is now symptom-free, is that antidepressants – despite the recent backlash in the media – significantly help millions of people. “I would never say, `Don’t go on it,’ ” she says. “I would just say be very aware that when you want to get off it, go to a doctor who knows about this.”