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"I'm a bad person and don't deserve to have any fun." "I'll never get the job, so I won't even apply." "This date will be a disaster because I'm ugly and stupid and no one will ever love me."
Patients suffering from depression are besieged by such thoughts, with the result that they're unable to enjoy much of anything. Their sleep and eating are disrupted, and they often have no energy for the simplest daily activities, let alone work or family.
Thanks to breakthroughs in understanding the brain chemistry underlying depression and in formulating drugs like selective serotonin reuptake inhibitors, or SSRIs, a standard of care for severe depression has evolved: Treatment guidelines for psychiatrists "call unequivocally for medication," says Robert DeRubeis, chairman of the psychology department at the University of Pennsylvania in Philadelphia.
But in the largest and longest-running study to pit medication against psychotherapy, Dr. DeRubeis and colleagues have found cognitive therapy -- which basically teaches patients to think about their thoughts differently -- is at least as effective as standard drugs in treating severe depression. The results of the study, which was funded by the National Institute of Mental Health and GlaxoSmithKline PLC, maker of the antidepressant Paxil, were presented at the annual meeting of the American Psychiatric Association in Philadelphia Thursday.
The findings have shocked hard-core "pharmaceuticals first" psychiatrists like Jay Amsterdam, a research psychiatrist at Penn and a co-author of the study. "I was a skeptic," he says. "I didn't think that in people with real, biochemically based depression, cognitive therapy would be effective. But I told Rob [DeRubeis], 'if you can fix my patients, I'll be a believer.' When I saw the result, I told him he had a highly effective treatment for depression, and that if he could bottle it he'd have a billion-dollar drug."
The results also run counter to those of an earlier study sponsored by the NIMH. In 1989, that three-site trial concluded that although cognitive therapy is as effective as drugs for mild depression, it is much less effective for the moderate-to-severe kind. The NIMH findings remain hugely influential, providing the basis for the drugs-first standard of care. In addition, other research has found that even if cognitive therapy helps initially, therapy patients face a higher risk of relapse than medicated patients.
In the new study, researchers at Penn and Vanderbilt University in Nashville, Tenn., randomly assigned 240 moderately-to-severely depressed patients to one of three groups. One group received 16 weeks of cognitive therapy, consisting of two hour-long sessions each week with one of six psychotherapists at Penn or Vanderbilt. This form of therapy coaches patients to see that their thoughts of worthlessness and hopelessness are exaggerated, that it makes no sense to extrapolate current setbacks into the future, and that sometimes bad things happen to nice people. The second group received 16 weeks of paroxetine, an SSRI that GlaxoSmithKline sells as Paxil. The last group received eight weeks of dummy pills, or placebos.
After two months, 50% of the medicated patients had improved, as measured by a standard scale of depression, plus whether they were sleeping, eating and functioning better. So had 45% of the patients receiving cognitive therapy. Only 25% of placebo patients were getting better. After four months, the response rates for the first two groups were an identical 57%, while the placebo group still lagged behind.
"Cognitive therapy may work more slowly than drugs, but after four months patients receiving cognitive therapy fare just as well," Dr. DeRubeis says.
These "responders" kept it up. Patients who had undergone 16 weeks of psychotherapy, but then had only three or fewer "booster" sessions during the next year, did even better than those who remained on drugs. Of those who had received cognitive therapy, 75% avoided relapse, compared with 60% of patients on medication. "This suggests that cognitive therapy has an enduring effect that protects against relapse," says psychologist Steven Hollon of Vanderbilt, a co-author of the study. "It looks like people walk away from psychotherapy with something they can use for life."
A key unanswered question is which patients will respond better to drugs and which to talk therapy. Severity doesn't seem to determine that. Chronicity, however, does: The longer a patient has been depressed, the harder it is for cognitive therapy to help. That may reflect the entrenched nature of the depressive thoughts and the difficulty of changing the way the patient views them.
In addition, patients who also suffer from generalized anxiety disorder did better on drugs than with cognitive therapy. That concerns some proponents of pharmacological treatments.
"More than 50% of depression patients in actual clinical practice also have an anxiety disorder," says Prakash Masand, clinical professor of psychiatry at Duke University School of Medicine in Durham, N.C., and a consultant to GlaxoSmithKline.
Doctors are reluctant to recommend cognitive therapy instead of drugs for depression not only because of the influence of the earlier NIMH study but also because of concerns about cost and insurance. Despite the widespread belief that long-term psychotherapy is financially impractical, however, in the Penn-Vanderbilt study it cost an average of $2,250 for the four months that patients received it. Treatment with drugs, which patients took for 16 months, cost $2,590. But insurance reimbursement favors drugs, so most primary-care doctors prescribe one of the SSRIs for depressed patients. HMOs, Dr. DeRubeis says, typically cap psychotherapy sessions at four. Many other plans cover half of allowed psychotherapy costs but a much larger percentage of prescription costs.
Another concern is how quickly the effects of drugs and therapy kick in. "Early in the study, the Paxil group had higher response rates than the cognitive-therapy group, so when it most matters, in terms of getting better quicker, the drug group does better," Dr. Masand says.
The availability of competent cognitive therapists is also an issue. The patients in the new study received cognitive therapy from state-of-the-art centers, notes Steven Paul, a psychiatrist and group vice president at Eli Lilly & Co., maker of the antidepressant Prozac. They are less likely to find skilled therapists elsewhere. But, Dr. Masand says, antidepressants "are available in the smallest city in the country."
Write to Sharon Begley at sharon.begley@wsj.com
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