Antidepressants: The Pills We Can't Kick

Antidepressants have become the go-to drugs of many doctors treating women—not just for depression but also for insomnia, weight loss and migraines. Yet the prescriptions may be creating more problems than they are solving. Learn how to decide what’s right for you

by Ginny Graves
pills yield sight
Photograph: Illustrated by Oliver Munday

When Prozac Nation was published in 1994, the catchy title was a serious exaggeration. Now it couldn’t be more apt. Doctors today dole out antidepressants as if they were Halloween candy, using them to treat everything from blue moods to hot flashes to low back pain. And women are their best customers. Nearly one quarterof women ages 40 to 59 are on Prozac or another anti-depressant, a far greater percentage than in any other age group, according to a recent report from the Centers for Disease Control and Prevention.

Behind that astounding figure lies a disturbing fact: For several conditions, the case for antidepressants is iffy at best; they aren’t even effective across the board in treating depression, the illness they were designed to alleviate, and may not relieve the other problems—such as migraines—for which they are prescribed. Nor are these drugs risk free. “Antidepressants can be helpful under the right circumstances, such as when people are very seriously depressed or suffer from anxiety disorders. But you definitely don’t want to take one if you don’t have to,” says Ramin Mojtabai, MD, PhD, associate professor in the department of mental health at Johns Hopkins Bloomberg School of Public Health.

Yet a significant number of women are using antidepressants when other treatments might be more effective and safer. Here, what you need to know so you and your doctor can determine if these drugs are best for you.

The Antidepressant Revolution

In 2011, American pharmacists filled 264 million prescriptions for antidepressants, up more than 25 million since 2007, according to IMS Health, a health care technology and information company. How did these drugs get so popular?

The first antidepressants—tricyclics and monoamine oxidase inhibitors (MAOIs)—were discovered by happenstance in the 1950s, when doctors were looking for drugs to treat schizophrenia and tuberculosis, notes Alan Frazer, PhD, chairman of the pharmacology department at the University of Texas Health Science Center in San Antonio. “Doctors noticed they lifted patients’ moods,” he says. But no one ever wrote a book called MAOI Nationor Tricyclic Nation, and here’s the reason: Both now and when they were first introduced, MAOIs could cause serious, sometimes fatal reactions in users who eat foods like pepperoni and aged cheeses that contain the amino acid tyramine. And tricyclics are what pharmacologists call dirty drugs. “They bind to several receptors in the body and as a result cause unpleasant side effects, like dry mouth, blurry vision, drowsiness and weight gain,” Frazer says. Even modest overdoses of tricyclics can be lethal, so the only MDs comfortable prescribing them were psychiatrists, who closely monitored patients.

The picture changed in 1988, when Prozac hit the market. It’s an SSRI (selective serotonin reuptake inhibitor), which means it prevents the neurotransmitter serotonin from being reabsorbed by brain cells, leaving more of it in the synapse between neurons. Prozac is a cleaner drug. “It has side effects, and the longer it’s been on the market, the more those have become apparent. But there’s almost no risk of overdosing,” says Frazer. Over time, Prozac and its siblings became known as safe antidepressants, and that perception opened the door for doctors to prescribe them widely, not just for depression but also for a variety of other conditions. That makes many doctors nervous, for the following reasons.

Concern No. 1

Antidepressants are prescribed for many conditions besides depression and anxiety

When Andrea Burnett had trouble sleeping after breaking her back in a boating accident, her doctor prescribed Elavil, a tricyclic antidepressant that has a sedating effect but isn’t approved by the FDA to treat insomnia. The drug knocked her out but caused terrible nightmares and hallucinations, so after two weeks she stopped using it. She finally got the relief she was looking for when she started taking Tylenol PM to help her sleep.

Burnett’s doctor prescribed an antidepressant for an off-label use, which means that the drug was given for a purpose other than the one for which it was approved by the FDA. Because the drug was tested as an antidepressant, its efficacy as a sleeping pill was never established, and its effects on someone who is not depressed were never documented. The rapid growth in off-label prescribing of antidepressants—the practice increased 13 percent from 1996 to 2007—is one reason for the explosive increase in antidepressant sales. And women are often on the receiving end of these off-label prescriptions, commonly given for health issues that disproportionately affect them, such as sleep problems, hot flashes, chronic pain, migraines, fibromyalgia and PMS, according to a study in the Journal of Clinical Psychiatry.

Off-label prescribing is legal, ethical and widespread; one of the pluses is that it allows MDs some leeway in treating tricky conditions. But there are many situations in which other kinds of FDA-approved treatments work better than antidepressants used off-label. (See chart, page 126, “What Works and What Doesn’t.”) So why would a physician try an antidepressant off-label instead of a drug thoroughly vetted for the purpose?

One possibility is that some doctors are misinformed. A recent study discovered that many psychiatrists and primary care physicians believe there’s evidence to support off-label uses when there is actually very little or none. “In some cases, doctors even thought a drug had FDA approval for a particular use when it’s known to be ineffective for that purpose,” says Caleb G. Alexander, MD, codirector of the Johns Hopkins Center for Drug Safety and Effectiveness.

In addition, doctors may opt for lower risk over proven effectiveness. For instance, in treating insomnia, “many doctors are wary of benzodiazepines, the class of approved sleep drugs, because they can cause addiction if they’re overused,” says W. Vaughn McCall, MD, chair of psychiatry and health behavior at the Medical College of Georgia in Augusta. The dose of tricyclics that doctors typically prescribe for insomnia (as well as for migraine prevention, chronic pain and fibromyalgia) is far lower than what they’d use to treat depression, so while the medication can still cause troublesome side effects, it’s unlikely a patient would overdose.

Dealing with hot flashes also requires a risk-benefit analysis. Although estrogen is the most effective treatment and the only one that’s FDA approved, many women can’t or don’t want to use it because of the hormone’s potential to increase the risk of breast cancer. For that reason, doctors often prescribe, off-label, an SSRI or SNRI (serotonin-norepinephrine reuptake inhibitor).

Concern No. 2

Antidepressants may not be the best way to treat depression

You might think taking antidepressants for persistent low moods is a no-brainer, and the FDA has approved their use for that purpose, but don’t assume these drugs will effectively relieve depression, which affects almost twice as many women as men. A review of 30 years of data in the Journal of the American Medical Association(JAMA) found that SSRIs, the most frequently prescribed antidepressants, don’t work much better than a placebo for people whose depression is simply mild to moderate. “They’re only truly effective for people with very serious depression,” says Irving Kirsch, PhD, associate director of the program in placebo studies at Harvard Medical School. The majority of depressed people who take them feel better. “But that’s because they believe the medication will work, not because it’s a chemical cure,” Kirsch asserts. (Many psychiatrists disagree with Kirsch and point to flaws they see in the relevant research.)

Why does it matter whether anti-depressants are effective drugs or just placebos, as long as they do the job of lifting mood? Two reasons: (1) The drugs often cause side effects that can significantly affect people’s lives, and (2) there isa safe and equally effective alternative for treating mild or moderate depression. Psychotherapy works as well as -medication—each helps 50 to 60 percent of people feel better—and has one big advantage over pills: It may protect you from a repeat bout of depression.

In contrast, researchers recently found that discontinuing an antidepres--sant can make you more susceptible to a relapse of depression in the ensuing three months. “Our theory is that brain chemicals that affect mood, like serotonin and norepinephrine, are maintained in a balance,” says Paul Andrews, PhD, assistant professor in the department of psychology, neuroscience and behavior at McMaster University in Hamilton, Ontario. “Antidepressants artificially increase those chemicals, so when you stop taking them, the body’s control mechanism causes the neurotransmitters to plummet to lower-than-normal levels, and that causes a relapse of depression.”

While that theory is far from proven, it’s true that the risk of relapse is lower in those who participate in psychotherapy than in those who take drugs. “Anti-depressants are like aspirin for a headache. They only work as long as you’re on them,” says Steven D. Hollon, PhD, a professor of psychology at Vanderbilt University. “But cognitive behavior therapy seems to have enduring effects. People who do just therapy have half the relapse rate of those treated with medication alone.” The most plausible explanation: Therapy teaches you skills that help you deal more effectively with your negative thoughts and daily stresses.

Despite these findings, antidepressant use has soared while the percentage of patients opting for talk therapy has tumbled. One study found that among people being treated for a mental-health issue, 57 percent used medication only while just 11 percent used psychotherapy alone, and about a third used the two treatments together. “One reason is financial,” says Mark Olfson, MD, a professor of clinical psychiatry at the Columbia University School of Medicine. “Insurance companies have more generous coverage for antidepressants than for psychotherapy, so patients who want therapy have to pay more out of pocket.”

Concern No. 3

Most of the prescribing is being done by primary care physicians

Primary care physicians write four of every five scripts for antidepressants—which is a problem, because PCPs tend to be less familiar than psychiatrists with the approved or effective uses of antidepressants. That’s not a slam on primary care doctors. Most simply haven’t been trained in the nuanced pharmacology of the drugs, nor do they have time to keep up with the constantly changing literature. Besides, many have seen their patients improve on the medications, which may happen partly because of the placebo effect. But PCPs’ lack of knowledge can also lead to some patients’ winding up on the wrong drugs.

Some primary care doctors, for instance, prescribe SSRIs for migraines. “But many headache specialists believe they may actually worsen the condition in some patients,” says Andrew Charles, MD, director of the Headache Research and Treatment Program at UCLA’s David Geffen School of Medicine. The trouble is, that kind of information hasn’t filtered out from the community of specialists into the larger world of general practitioners.

Concern No. 4

Side effects may be more problematic than many patients and doctors believe

The early studies of SSRIs followed people for only six to eight weeks and came up with a few reported side -effects—mostly nausea and vomiting—that tended to disappear quickly. Now that these antidepressants have been on the market for more than 20 years, a fuller picture has emerged, and it shows some serious drawbacks. For example, about 40 percentof people taking SSRIs have problems with desire, arousal or orgasm. Although it’s been less well examined, a feeling of emotional numbness may be common in a subset of patients; in a small study, researchers at Case Western Reserve University School of Medicine found this condition in 80 percent of patients taking an SSRI who complained of sexual dysfunction. Also, many people gain weight on anti-depressants. The amount depends on the specific drug you take. Full doses of tricyclics, for instance, often cause users to gain more than 7 percent of their body weight, and even reduced doses are known to expand waistlines.

Moreover, there’s preliminary evidence that antidepressants may have even more dire effects. According to recent research, it’s possible that antidepressants increase the risk of everything from headaches to irritable bowel. Last year a study from Beth Israel Deaconess Medical Center in Boston found that patient mortality in the intensive care unit was 73 percent higher in those taking antidepressants.

“Serotonin regulates numerous processes, including your moods and sodium balance in your blood, and it appears that messing with that system can take a toll on how the body functions,” says Andrews. “We don’t know for sure, but it’s likely that the higher the dose and the longer you’re on antidepressants, the riskier they are.”

In light of the potential risks and drawbacks, ask your doctor about any antidepressants she prescribes. “Physicians are often too rushed to review all the pros and cons with patients, but you deserve some time and attention,” says Steve Balt, MD, a psychiatrist and editor-in-chief of The Carlat Psychiatry Report, a monthly newsletter for psychiatrists. If you can’t get all your questions answered in your initial appointment, schedule a follow-up to talk about your options, or see someone who specializes in your problem. “Antidepressants can be a viable option, but they need to be considered alongside all the other options—psychotherapy, other medications—if you want to make a truly informed decision,” Balt advises.

Next: What to Ask Before You Swallow Pills

Plus, check out this chart that shows what works and what doesn't.

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First Published Fri, 2013-02-01 11:02

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