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For many Americans, antidepressants can be a lifesaver. But others complain that the drugs take the edge off their memory, concentration, creativity, and drive. Is this true? Are the wrong people getting the medication? Are the wrong doctors prescribing it?
I made an appointment to see an endocrinologist because something told me that my hormones had taken leave of their senses. I was only 40, but strange things were happening. I was fatigued and anxious, I'd lost my appetite, I couldn't sleep, my thick blonde hair had started to thin and turn gray, my skin was itchy-dry, and I wondered if I could make it through the day. Friends were concerned about my precipitous weight loss; I'd slipped past lithe to something on the order of skeletal.

The doctor ordered a blood panel, and the results were all within normal range. There was no evidence of thyroid dysfunction or the onset of perimenopause. I was suffering from depression, she suggested, and although it might be wise to get some psychotherapy, she'd be happy to write me a prescription for antidepressants. I filled it and dutifully began swallowing the pills. I had plenty of friends who were taking antidepressants, and I looked forward to developing a certain resilience, as they had. Soon, I thought, stress would roll off me like water off a duck's back.

But that didn't happen. Before long whatever zest I'd had for work and family disappeared. My emotions seemed to vanish, and with them, my sense of humor. One morning a little more than a month later, in the middle of an important meeting, I lost track of four out of the six key points I'd rehearsed the night before. The names of three coworkers around the conference table also evaporated into thin air. Under pressure I was usually as sharp as a buzz saw. It had to be the drug. After the meeting, I dashed to my office, twisted open the vial of pills, and dumped them into the trash.

Last year, as part of my research for a book about memory, I decided to find out whether antidepressants could engender cognitive side effects, such as changes in motivation, memory, and concentration, or if what happened to me was a metabolic fluke. With barely any research published on the topic, I started rather unscientifically by asking around: Were other people troubled by such symptoms? Most said no; antidepressants actually made them more clearheaded and animated. But I'd read that the novelist John Irving (The World According to Garp) stopped taking one of these drugs after concluding that it made him feel detached and dulled his urge to write. And when I posted inquiries on a few websites, including, within hours I found I was not alone.

I feel emotionally castrated because not only do I not have negative feelings, I barely feel anything at all. I'm an artist who can no longer draw or paint or create. Instead, I sit around and do absolutely nothing.
— B.J. Cade, 53

I have been on antidepressants for the past 20 years or so. I started taking them after my second divorce. I am currently weaning myself off medication because I have no zest for life. My edge is gone. It's a subtle loss, and it is not always realized. I want me back.
— Kathy Costello, 58

I have been on a combination of more than 20 different types of antidepressants, anxiety medication, antipsychotics, and sleeping pills (not all at one time!), and was eventually able to go off everything but my antidepressants and an OCD drug. I have no memory left—if I don't write things down, I immediately forget them. I am trying to go back to school to pursue a dream, but I can no longer get myself to function well enough to pass the GRE. I went from scoring at about the 80th percentile several years ago down to the 59th percentile. I'm trying to make changes, but I am so unmotivated that I am literally appalled at myself—and I know it's the meds.
— Christine Giffin, 33
Before I went on antidepressants for four years, I was outspoken and opinionated. I lost all that. I was allowing my life to be mediocre—letting it just evolve around me. I've been off medication for the last ten months, and since then, I've returned to school so I can study law, signed up for dance classes at Arthur Murray, started traveling—even that had slacked off. I've got my drive and heated passion for life back. It's wonderful.
— Tracey Coppotelli, 43

One after another, the e-mails came in. Whether unremitting depression itself was responsible for the memory loss and apathy or whether these cognitive side effects were somehow related to the drugs was devilishly hard to say. But as I dug in, talking to many of the top experts in the field—psychologists, psychiatrists, neurologists, psychopharmacologists, government researchers, academics, and drug company representatives—it became clear that this question was a legitimate one to be asking.

To back up for a moment, it's almost impossible to adequately emphasize how valuable these drugs can be. Often whatever side effects they may produce are a small price to pay for individuals with specific types of recurring psychiatric problems, including clinical depression, anxiety, panic, and bipolar disorders. "The drugs allow people to carry on with their lives," says Peter Kramer, MD, the author of Listening to Prozac and Against Depression. Untreated depression is dangerous. Fifty to 60 percent of individuals who've had one bout of major depression will have another; for those with two episodes, there is an 80 to 90 percent chance of a third. In a recent essay, Kramer wrote, "Research shows depression to be an aggressive, destructive process. A variety of studies suggest that it is linked to progressive damage in the brain … Nor is the brain the only organ at risk. Scientists have found depression to be correlated with heart disease, bone fragility, abnormalities of endocrine glands, and changes in blood elements."

But for some of these patients, antidepressants aren't helpful. According to the largest clinical trial on depression to date, funded by the National Institute of Mental Health (NIMH), only about half of "real world" patients with major depressive disorder had a significant response after taking an antidepressant for 12 to 14 weeks. (About 30 percent achieved full remission, which is in line with other studies, and another 10 to 15 percent found their symptoms reduced by at least half.) An estimated 20 percent of people with major depression fail to improve even with multiple treatments—different medications, therapy—according to various experts, including researchers at Columbia University Medical Center.

Yet the drugs are such an effective and easy solution for milder depression, they're readily prescribed—and sometimes, experts worry, overprescribed. Joseph Glenmullen, MD, a clinical instructor in psychiatry at Harvard Medical School, believes the majority of antidepressants are handed out to people who don't need them—many suffering from distress over a specific event such as divorce, illness, or a death in the family. "Physicians have become so comfortable with using these medications," says William Prey, MD, a San Francisco neuropsychiatrist, "they're prescribing them to treat conditions that would have previously merited a stiff upper lip." As one government expert, Matthew Rudorfer, MD, acting chief of the NIMH's Adult Interventions branch, puts it, "If there is a real condition there that warrants a diagnosis, I wouldn't want to miss it. But a lot of these cases that present for treatment are common problems of everyday living, and we are labeling them as pathology."
In the 1950s and '60s, only people with severe symptoms were labeled as depressed. The drugs used, tricyclics, says Rudorfer, were "potentially toxic to the heart and extremely dangerous if you overdosed on them. Anyone who took these drugs required a lot of time and attention from physicians—repeated visits and regular dosage adjustments. Prescribing them was generally restricted to psychiatrists. They were used in anything but a casual fashion."

Since the late '80s, when the new antidepressants started hitting the market—SSRIs, which boost serotonin, and related drug classes like SNRIs that also affect other brain neurotransmitters—the medical community has been prescribing them without a psychiatrist's input. As a result, according to The Wall Street Journal, 75 percent of prescriptions for antidepressants are written today by primary care physicians, most of whom have little training in diagnosis and management of psychiatric disorders.

Meanwhile, there is no shortage of patients. In June, a much-publicized survey funded by the National Institute of Mental Health suggested that one in four people experiences a mental disorder during any given year, and half of Americans will have one during their lifetime. How, as a nation, have we come to suffer such a widespread psychological affliction?

"I expect we're going to find that the definition of mental illness has been too broadly drawn," says David Kupfer, MD, chairman of the department of psychiatry at the University of Pittsburgh Medical Center and extremely influential in his field. "When I heard about the results of this study, I thought I'd be spending all my time taking care of patients."

With antidepressants now being used to treat not only depression but an ever-expanding variety of conditions (shyness, eating disorders, premature ejaculation, sexual addictions, smoking, premenstrual syndrome), they've almost gained the status of all-purpose wonder drugs. As Andrew Solomon, the author of The Noonday Demon, a brutally honest and much-heralded tome on depression, noted in a recent article, there are "people with an inflated idea of how happy we should be, who want to medicate away their personalities." My question is: At what cost?

I began to check with clinical psychologists and psychiatrists as well as psychopharmacologists (experts at prescribing psychoactive medications) and academics studying patients and drugs. Charles Nemeroff, MD, chairman of psychiatry and behavioral sciences at Emory University in Atlanta, who has spoken on behalf of several antidepressant drug companies, estimated that between 15 and 20 percent of his patients on medication complain of emotional blunting, although most would prefer that to severe depression. "Someone will say that she loved to play the piano, that it was her greatest pleasure in life, but that she can't get interested in it anymore."

Harvard's Glenmullen, whose books Prozac Backlash and The Antidepressant Solution both address the side effects of these drugs, added, "We've known about cognitive side effects of SSRIs for more than a decade. Often they creep up slowly. And if nobody's watching, the patient can make all kinds of assumptions about the nature of these changes—that this is who he or she has become."
At Columbia, David A. Kahn, MD, clinical professor of psychiatry at the university's medical center, gave a similar response. "There is a small group of patients on the drugs—and I can only guesstimate this at about 10 to 20 percent—who will feel slightly off in terms of trouble with recent recall or finding the right word or remembering a name. It's not their imagination." Some people may also feel sedated or apathetic on many antidepressants, he says, although the newer drugs, which act on multiple neurotransmitters, tend to give people more energy (they still can affect word-finding and memory abilities). "For the most part, the improvement in daily functioning and thinking that comes with treating depression leads to a net gain," Kahn said. "But occasionally the cognitive problems are serious enough to warrant stopping the medication. The point for patients and doctors to be aware of is that it can happen, and if it does, not to scoff at it or dismiss it but to experiment and perhaps switch medications."

Kahn sent over a recent study from a journal called Human Psychopharmacology: Clinical and Experimental on SSRIs and cognitive performance in young patients (their youth—mean age, 32—being important because it ruled out memory loss due to normal aging). The article shows "how equivocal the literature is," he said, "but with a trend toward acknowledging that some people do experience cognitive side effects." The study found that compared with a control group, patients on the drugs showed more memory impairment, including delayed recall; yet the researchers were careful to allow that the results might also be due to the subjects' underlying depression not being fully treated.

After I asked several of the pharmaceutical companies for their take on whether antidepressants cause memory problems or dulling of drive, one spokesperson stated, "The cognitive side effects you reference do not meet the statistical threshold determined by the FDA for inclusion in package literature or patient information." In other words, pharmaceutical companies have no obligation to report or disclose cognitive side effects when there's insufficient data to prove that the drugs cause the symptoms, according to government standards. And he's right, says Susan Cruzan, a media representative at the FDA: A side effect would only be included in patient information if it occurred in at least 5 percent of participants in the trial, and at twice the rate of those in the placebo group. She checked with Thomas Laughren, MD, FDA division director for psychiatric products, who offered this: "The events you are focusing on do not emerge from controlled trials as drug related and that is why they do not get any prominence. In fact, currently used antidepressants are not thought to have cognitive side effects."

The studies required for FDA approval of these drugs, however, generally lasted six to eight weeks, and it often takes much longer for side effects to become apparent. Only recently, for instance, has increased risk of suicide been identified as a possible side effect of antidepressants. In June the FDA put out a public health advisory, noting that several scientific publications have now suggested there is a relationship between taking the drugs and suicidality in adults (the agency has already started requiring manufacturers to add a black box warning for children and adolescents on antidepressants). The FDA announced that it is currently going over hundreds of clinical trials on antidepressants for signs of suicidality, which did not show up in the initial analyses. In the meantime, it warns that adults on these drugs should be watched closely for suicidal thinking or behavior, this being "especially important early in treatment or when the dose is changed, either increased or decreased."
Every drug has side effects, and for many patients, the benefits of antidepressants far outweigh any cognitive downsides. Becca Moran, 32, who complained of serious memory problems and numbness while on medication for depression, says, "I can't help but remember the night—before I went on antidepressants—when I was suicidal, about to kill myself. Compared with those feelings, I will take memory loss, poor sex drive, and general emotional give-up any day."

But side effects do become an issue, for example, when they are more debilitating than the original problem the drugs were prescribed—sometimes inappropriately—to treat.

Megan McCoy (not her real name), 34, who has four children under the age of 9 and works part-time, wrote on a post to that she had been on various antidepressants for the past two years. All of them made her numb and apathetic. "I felt like I was sleepwalking through my life. I had no drive of any kind."

After reminding her that I was only a journalist, not a mental health professional, I took a wild guess and suggested that rather than depression or the drugs, maybe the pressure of raising four young children while working was causing her problems. (To confuse the issue, chronic stress can wreak havoc with mental abilities, exposing the brain to relentlessly high levels of cortisol, a hormone that slowly impairs the hippocampus, which controls learning and memory).

"Not really," she said. "My kids are great. It's my husband. His primary care doctor put him on a stimulant for adult attention deficit disorder. And then a psychiatrist put him on antidepressants and antianxiety meds. When he comes home from work, he goes directly to bed. He used to do the yard, clean the garage, play with the kids. Now the man is barely functioning. The only decent time we have together is in the morning, when we have coffee.

"The reason I want to be off these drugs is so that I am not—ever—like him. But I feel I have to stay on something so I can stay above water and keep everyone happy." Her misery was palpable.

Becki Kurschinske, 20, also wrote in. The mother of an 18-month-old daughter, she had been taking one of the SNRIs. "I stopped doing the laundry and the cooking. My husband had a lot of trouble getting my attention. My mother often asked me what was wrong because I would sit on her couch, spaced out. I could stand in the middle of the living room for five minutes staring at the door, trying to remember if I did everything I needed to do to leave. I couldn't read a book for more than ten minutes before I realized that I'd stopped turning the pages."

As with Megan McCoy, Kurschinske first assumed that her problems were drug side effects. But when I phoned her, she told me that in the months that had elapsed since she posted on the Web, things had changed. A 120-mile round-trip commute to her job as an administrative assistant for Boeing had kept her away from home 12 hours a day for the first year of the baby's life. Her time with the child consisted of waking her up and putting her to bed, and then getting up to feed her in the middle of the night. The symptoms had abated when Kurschinske found a new part-time work arrangement. "I thought the drugs were making me feel so spacey," she says, "but now I think it was the way I was living my life."

Many of the people I talked to, it seemed, were medicating themselves to accept difficult situations they felt powerless to change—family problems, financial pressure. The drugs were supposed to buck them up and help them move on, but ironically the resulting low energy and lack of motivation worked against them.
Cognitive side effects also wouldn't be of such concern if they were short-lived. But many patients go on these drugs for years, even decades. "If, as was once done, you merely give antidepressants for, say, a few weeks, to interrupt an episode of depression," says Peter Kramer, "you do not hear complaints about loss of libido or ambition—only reports of gratitude for the remission of symptoms." But doctors now know more about the gravity of depression—that it often recurs and causes serious damage to both brain and body. As a result, he says, "these medications are given longer and in fuller doses than in the past."

There are currently no definitive guidelines for when depression should clear up after a patient starts on medication, but several doctors mentioned four to six weeks as average for seeing significant improvement. Once the disorder remits, the American Psychiatric Association recommends continuing treatment for a minimum of 16 to 20 weeks to prevent relapse. Experts agree that long-term medication is not necessarily appropriate after a single bout of depression, which means patients kept on antidepressants for years should be questioning why. And anyone whose drug cocktail includes antianxiety meds may get a double whammy: Benzodiazepines like Ativan and Xanax list "memory impairment" as a possible adverse reaction on their package inserts.

Many in the field would like to see much more emphasis on psychotherapy, in particular short-term cognitive behavioral therapy, which studies have shown to be very effective. Originally, the idea of medication, says Glenmullen, "was to improve the patient's emotional state to the point where he or she could begin to initiate changes in his or her life, often with the help of psychotherapy. Somehow that thought was lost, replaced with the idea that the drugs alone can do the job."

Also lost, experts argue, is the idea that patients should be monitored for as long as they're on antidepressants. "I think of using these medications as turning dials on the control panels of the brain," says Prey. "There is the need for constant and very precise tuning, because people don't stay the same." Richard Friedman, MD, director of psychopharmacology at Weill Cornell Medical Center, stresses, "It's not necessary to choose between feeling emotionally well and living with cognitive side effects, or stopping the drugs and getting depressed. That's a false choice. A good clinician asks about side effects and tries to adjust the medication. Sometimes that means lowering the dose; sometimes it means switching to a different drug."
Patients who receive medication after being diagnosed with major depression should have three or more doctor's visits in the first 12 weeks, according to guidelines developed by the National Committee for Quality Assurance (NCQA), a private, not-for-profit organization dedicated to assessing and reporting on managed care plans. That happens, however, just 20 percent of the time. It's easy to lay the blame on the primary care doctor or HMO, but just as often, the patient fails to show up for appointments, coming in only when the prescription can no longer be refilled.

Most experts agree that treatment of a mood disorder should also include increased exercise, which, along with cognitive behavioral therapy, has been proven in some studies to be at least as effective as antidepressant treatment—and it comes without side effects. "Turn off the computer or the TV and get a decent night's rest," suggests Prey, who is convinced that much depression arises from too little sleep, resulting in a malfunction of the body's circadian clock. Many doctors recommend meditation to reduce anxiety and, as some research suggests, to boost mood. Studies have also shown that eating more omega-3 fatty acids can make a difference. Finally, consider that what seems like depression may be due to an imbalance of thyroid, reproductive, or adrenal hormones, says Richard Shames, MD, the author of a recent book about endocrine imbalance called Feeling Fat, Fuzzy, or Frazzled?

It took almost a decade for me to get to the bottom of the problems that originally sent me to the endocrinologist. Eventually, I learned that my thyroid level had been tripping me up. (Reexamination of my records showed that I'd been at the very low end of normal at that first assessment, and, at least to my new doctor, my thyroid-related symptoms had been as clear as day.) I began taking a small amount of synthetic thyroid hormone. Within weeks I was sleeping well, my weight stabilized, my skin stopped itching, my hair began to grow back, and I usually had enough energy to make it through my busiest days.

Whether antidepressants are right for you, only you and your physician can decide. What's clear to me, however, is that the choice to get on them is not something to be entered into lightly. Nor, I should stress, is the decision to go off them—it's crucial not to quit suddenly.

With my physical symptoms under control, a number of people—after many years of greeting me with distressed expressions on their faces—have started to tell me that I look really well. I think they're right. Still, there are days when the stress level builds, everybody needs everything ASAP or faster, the tension in my shoulders grows, and I am convinced that I am falling into a bottomless pit from which I will never be extricated. These are the kinds of feelings that typically describe depression. But I know that—at least for me—this, too, shall pass. My emotions, my motivation, and my intuition are among the personal characteristics I hold dear. There is no way I'd trade them for the promise of life on an even keel.


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