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Doctors Weigh In On Antidepressants

From Pittsburgh Post-Gazette (PA), Feb. 17--Tom Cruise famously denounced them on the "Today" show. In books like "Listening to Prozac," "Prozac Nation" and "Prozac Backlash," they were proclaimed as either a wonder drug or a personality-numbing crutch.

Now comes Newsweek’s Feb. 8 cover story, suggesting that antidepressants like Prozac, and its descendants, Zoloft, Celexa, Paxil, are actually a lot less than they’re cracked up to be.

"Anti-Depressants Don’t Work," the story’s headline proclaims, citing new research that shows these widely prescribed drugs are no more effective for mild to moderate depression than a sugar pill.

Is this real news, or just the latest salvo in the long-running debate that has simmered since the late 1980s, when Prozac was first introduced? Back then, SSRIs, or selective serotonin reuptake inhibitors -- were described as a new breed of drug, relatively free of side effects compared to their predecessors. By 2005, they were prescribed to nearly 27 million people -- more than twice that in 1996.

But an article in January’s issue of the Journal of the American Medical Association reviewed six large drug trials involving two types of antidepressants: SSRIs and another class of drugs known as tricyclics, and found that for moderate to mild depression, placebos worked almost as well. A real difference was found only in the most severe cases of depression.

And in a new book, "The Emperor’s New Drugs: Exploding the Anti-Depressant Myth," psychology professor Irving Kirsch cites his own studies and others that came up with the same result -- that the very act of taking a pill, whether it’s real or a placebo -- has been found to improve mood.

"These drugs work because people hope and expect they will," said Dr. Kirsch in a telephone interview from his home at the University of Hull in England. "The core of depression is hopelessness, and anyone feeling a sense of hope that comes from treatment is probably going to feel better. But these studies are telling us that there is probably not a chemical effect involved."

Dr. Kirsch said he’s not advocating people stop using antidepressants if they feel they help, but he notes that a course of psychotherapy for 15 to 20 weeks works as well as a placebo or medication -- and without a drug’s side effects, which may include loss of libido, nausea or insomnia.

In fact, his and other studies have had an impact in Britain, Dr. Kirsch says. The National Health Service has shifted its emphasis toward the use of psychotherapy -- training 10,000 new therapists in cognitive behavioral or problem-solving therapy -- as a first line of defense in treating mild to moderate depression. In Britain, at least, it’s cheaper and as effective to train therapists -- and ultimately less expensive than maintaining patients on medication, he said.

That’s not the case in the United States, where many physicians who prescribe these drugs aren’t trained in psychotherapy -- which isn’t covered by many insurance plans anyway -- and many therapists aren’t permitted to prescribe these drugs, so patients tend to fall between the cracks.

"It’s a function of economics," said Ellen Frank, professor of psychiatry and psychology at the University of Pittsburgh School of Medicine, noting that it’s far less expensive for insurers to pay for an occasional doctor’s visit than having 12 sessions of psychotherapy.

Ideally, "what these results do suggest is that maybe most patients, mildly to moderately depressed patients, should begin with psychotherapy, and if that isn’t helping sufficiently, then we should go to the addition of medication," she said.

Nonetheless, she and other psychiatrists question whether the JAMA study -- and Dr. Kirsch’s new book -- break any new ground, while, in psychiatric journals and academic centers, questions have been raised about the JAMA study’s methodology. The authors, led by Jay C. Fournier and Robert J. DeRubeis at the University of Pennsylvania, claim theirs is the first to delve deeply into data involving mild to moderate cases, rather than severe depression.

Others disagree.

"These basic findings are not new," said Michael Thase, a psychiatrist at the University of Pennsylvania who was not involved in the JAMA study, noting that more than 200 studies have been conducted into antidepressants.

"We’ve always known severe depression is more like an illness and you have a better chance of being helped by these drugs than you do if the depression is mild or moderate," Dr. Thase said, adding that other studies show medication "is one of several proven options, just as some psychotherapies are also proven options."

In any clinical trial, patients with depression might end up feeling better, regardless of whether they’re given a sugar pill or the real thing, added Dr. Frank, who also directs the Depression and Manic Depression Prevention Program at Pitt’s Western Psychiatric Institute -- whose reputation rests, in part, on its research into the biological roots of depression and the use of medication to treat mood disorders.

People suffering from depression may derive some comfort in participating in a study, Dr. Frank added, which involves office visits, questionnaires from sympathetic clinicians and meetings with doctors in an atmosphere of support and empathy.

"There is a whole lot that goes on in the human interaction between an experienced psychiatrist who is skilled at treating depression, and the patient," she said, noting that she has consulted with pharmaceutical companies about antidepressants.

In her own office, she said, "We select our secretary for her personality, her ability to reassure people, to calm them, to feel welcome. All of these things have an effect, which gets even bigger in the context of a randomized control trial." She noted that the placebo effect would probably vanish if the pills were given out by an ATM machine.

Most mental health experts acknowledge, however, that they don’t know why these medications work -- except that they do.

Daniel Schraeger, a local psychiatrist, said he’d been initially reluctant to prescribe Prozac when it first came out 30 years ago, but its benefits have proven themselves to him over time.

"At first I thought, well, I’ll try this, but it probably won’t make a difference," he said. "Then my patients started feeling better, and remained this way for years. This happened repeatedly, and it’s been a revelation to me. The exact mode of action remains unknown, but when something works, you use it."

The main concern about this latest round of anti-antidepressant literature is that it will discourage people from seeking treatment, added David Kupfer, longtime chair of the department of psychiatry at the University of Pittsburgh School of Medicine and director of research at Western Psychiatric Insitute of Western Pennsylvania.

"My own sense is that we as a society continue to do a very good job of stigmatizing these illnesses, these disorders, and this just makes it more difficult for people to accept that medication can positively affect the outcome of a depression, just as taking blood pressure medication will reduce those symptoms," said Dr. Kupfer, who has consulted with pharmacological companies about antidepressants.

Dr. Kirsch stressed that he’s not recommending that anyone wean themselves off these drugs willy-nilly, given the danger of withdrawal symptoms.

"If they’re happy, and there are some people who swear by these medications, if they’re not troubled by side effects, by all means, stay on them," he said. "But others need to know there are alternatives out there."

Mackenzie Carpenter: or 412-263-1949.

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Posted: February 2010