June 2, 2000 -- "I look so awful, I'm afraid to leave the house!" Maura, a graceful 39-year-old Irish woman, had been a psychotherapy patient of mine for about a year when she began developing strange, fluttering tics around her eyes. The tics eventually grew to include involuntary chewing motions and twitching of her lips. Her tongue darted in and out uncontrollably. She wore sunglasses and scarves to cover the disfiguring movements.
What happened to Maura is called "tardive dyskinesia," and it's one of the most worrisome side effects of many psychiatric drugs prescribed in America, including Prozac. Maura's primary care physician had put her on Prozac two years earlier because she'd been feeling anxious and weepy whenever she drove on highways. A year after that, she became my psychotherapy patient, and after she successfully completed therapy, we began cutting back on her Prozac prescription.
Still, what had started as mild facial tics became uncontrollable symptoms that confined Maura to her house. It took six months for the worst of these disfiguring tics to subside. She still has twitching around her lips.
Doctors are now seeing side effects with Prozac indicating a range of loss of motor control: tics, twitches, muscle spasms, immobilizing fatigue, and tremors. While this drug is marketed as a panacea, and the public's general impression is that it brings only incidental side effects, Eli Lilly and Co.'s (Prozac's manufacturer) official product information acknowledges that tremors alone occur in 10% of patients on Prozac. (Any side effect occurring in 1% or more of patients is acknowledged as "frequent" by the pharmaceutical industry.)
More than 28 million people have taken Prozac and other related antidepressant drugs such as Zoloft, Paxil, and Luvox, which are thought to increase levels of serotonin, a chemical messenger in the body associated with mood, among other things. Of these, about 70% get their prescriptions not from psychiatrists trained in diagnosing and treating depression, but from primary care physicians who often have neither the time nor the expertise to fully evaluate their patients' mental health and advise them about different therapies. Many primary care doctors aren't happy with this state of affairs, but they feel pressured by health insurers not to refer patients to specialists.
The "if depressed, then Prozac" model puts millions of people needlessly at risk of serious side effects. The most dangerous of these is an "overstimulation reaction" that has been linked to compulsive thoughts of suicide and violence. This risk of suicidal thoughts, which occurs in an estimated 1% to 3% of patients, so alarmed the German equivalent of the U.S. Food and Drug Administration that a warning appears in Eli Lilly and Co.'s official information on Prozac in Germany.
Suicidal thoughts and loss of motor control are not the only side effects of these antidepressants. Others include:
- Severe withdrawal. It can take patients months to wean themselves off an antidepressant like Paxil without suffering symptoms such as dizziness, anxiety, and difficulty balancing.
- Significant weight gain, often after initial weight loss.
- A loss of effectiveness. Prozac, for example, wears off in about a third of patients within a year.
- Sexual dysfunction, reported in as many as 30% to 60% of patients.
These important concerns are downplayed by Prozac's manufacturer, Eli Lilly and Co. Moreover, the published risks are based on short-term studies. No one really understands how normal functioning of the brain may be impaired by Prozac-type antidepressants in the long run. Indeed, one worrisome study, published in the March 2000 issue of Brain Research, indicates that Prozac and Zoloft may be toxic to the very cells they target in the brain.
Does this mean that no one should take these antidepressants? Emphatically not. I still prescribe Prozac and related medications for patients in my practice. I've seen firsthand the benefits they offer. But any drug that also has the potential for serious harm should be prescribed only by experts, and then only with restraint and careful monitoring.
Patients should have moderate to severe depression symptoms that affect them to the point that they risk real damage -- the loss of a job or a relationship, or the abandonment of an important goal -- before they consider starting antidepressant medication. Even then, these drugs should be used in combination with other types of treatment, like psychotherapy, couples therapy, or 12-step programs in order to ultimately reduce long-term dependence on the drug.
If your doctor suggests an antidepressant, ask for a referral to a psychologist or a psychiatrist for a second opinion. And should you start taking the drug, don't just blindly renew your prescription over the telephone. Sit down with your physician every six months or so to reassess your situation. Ask questions: Do you still need it? Can you lower your dosage?
As Maura learned the hard way, these antidepressants are not right for everyone. Don't accept the risks they may pose lightly.
Joseph Glenmullen, MD, a clinical instructor in psychiatry at Harvard Medical School, is on the staff of Harvard University Health Services and has a private practice in Harvard Square. He is the author of Prozac Backlash: Overcoming the Dangers of Prozac, Zoloft, Paxil, and Other Antidepressants With Safe, Effective Alternatives.
By Frederic Quitkin, MD
June 2, 2000 -- In the wrong hands, the scariest volume of horror stories in the world can be the Physician's Desk Reference -- the guide to drugs and drug interactions found in every doctor's office. I could take any commonly prescribed drug listed there, run through the list of possible side effects, and frighten any patient away from taking it.
No matter how benevolent and time-tested a medication, it will have side effects. If you consider those side effects out of context, without proper background, you might well be convinced that the drug is going to harm you, not help you. You might therefore give up the allergy medication that lets you go outside in the summer, the beta-blocker that helps control your heart failure, or the drugs that help stabilize your diabetes -- all based on "side effect panic."
Sound farfetched? Not really. In the wake of overhyped publicity about the side effects of antidepressants, spawned by Joseph Glenmullen's new book Prozac Backlash, I fear such panic will strike thousands of people whose daily lives are immeasurably better thanks to the prescription of antidepressants that are thought to regulate brain levels of the chemical serotonin in our bodies. These drugs, commonly known by brand names such as Prozac, Zoloft, and Paxil, have been carefully studied and are closely regulated. But you wouldn't know it to read the book by Harvard psychiatrist Glenmullen, MD, who paints a distorted picture of a psychiatric Wild West in which anything goes when prescribing these antidepressants.
My colleague at Yale, Harvey Ruben, MD, tells the story of a young man who came to him and said, "I've got to stop my Prozac." Why, he was asked, when he felt so much better since he'd been on it? "My fiance says she won't marry me if I don't go off Prozac. She's afraid I'll kill her." The woman's fears weren't based on his behavior, but on stories she'd picked up in the media about extreme (and rare) side effects such as neurological problems, loss of sexual function, and psychosis. Based on such reports, the young man had to choose: his fiance, or his mental health.
This story illustrates the dangers of a book like Prozac Backlash. It takes individual instances of known but rare side effects -- tremors and weight gain, as well as psychosis and sexual dysfunction -- and blows them out of proportion. Yes, side effects should concern both patient and physician, but they must be placed in proper context. Instead, Glenmullen exaggerates the risk. Indeed, some of the researchers whose work Glenmullen cites in the book, such as University of Massachusetts psychiatry professor Anthony Rothschild, MD, have warned that the book misrepresents their work.
Prozac Backlash and the antidepressant "chorus of doom" that accompanies it may unnecessarily frighten patients for whom antidepressants have been a godsend. Worse, they may choose to give up their medications -- risking far more serious personal, emotional, and medical problems than are posed by the comparatively small possibility of side effects.
Part of the problem is that the antidepressant critics see a symptom occur after a patient has taken Prozac and label it a side effect. Yet often we can't know if the symptom was actually caused by the drug. Consider suicide: Studies have shown that 15% of people with unsuccessfully treated clinical depression will commit suicide in their lifetime -- Prozac or no Prozac. So it's no surprise that Glenmullen found a handful of people who have considered or attempted suicide while on Prozac. It simply shows that we're dealing with a group of people who are very ill and who may attempt suicide regardless of what treatment they are given.
The antidepressant naysayers also point to a small body of research that, they say, shows that the benefits patients experience on antidepressants are no greater than those they might get taking a placebo or through other kinds of therapy. That is hogwash. About 60% to 70% of studies show that antidepressants outperform placebos in reducing and managing depression. The likelihood of such a result happening by "accident" is remote.
Do antidepressant side effects exist? Of course they do, and they must be taken seriously. Do some physicians prescribe antidepressants without careful diagnosis and evaluation of the patient's condition? Unfortunately, that is also true. Yet this carelessness is not a common occurrence, and it is better remedied by ongoing education of physicians.
A book that discussed responsible use of antidepressants wouldn't be a danger -- it would be a public service. But something called Prozac Precautions wouldn't fly off the shelves as Prozac Backlash has. At what cost? I, for one, am deeply concerned that as a result of this overhyped book, people with serious depression may forgo the treatment they desperately need.
Frederic Quitkin, MD, is a professor of clinical psychiatry at Columbia University College of Physicians and Surgeons and director of the Depression Evaluation Service of the New York State Psychiatric Institute at Columbia Presbyterian Medical Center.
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