Depression is a chronic illness with recurring episodes. So should we deploy antidepressants battle by battle, or order them in for the long war?
When Sheila Singleton, 45, filled her first prescription for an antidepressant, she assumed it would also be her last. "I thought OK, when the pills work and get myself straightened out, I'll go back to taking nothing but my vitamins," she says. Seventeen years later, Singleton still pops a pill every day. During the brief intervals when she's gone off medication, or when the ones she was on stopped working, the depression returned with a vengeance.
Among the newer antidepressants, options range from SSRIs (selective serotonin reuptake inhibitors) such as Prozac, Paxil, and Zoloft, to those—Wellbutrin and Effexor, for example—that target different or combined neurotransmitters. Most satisfied patients claim they provide highly effective relief with few side effects.
But there is one notorious downside: roughly 70% of SSRI users are plagued by sexual difficulty. "It's a big problem," acknowledges Donald Klein, M.D., professor of psychiatry at Columbia University and director of research at the New York State Psychiatric Institute. "There are no hard data on how many people actually discontinue treatment due to the sexual side effects; it largely depends on how they are handled by the specific doctor. Zoloft, for example, is short-acting and can be stopped for a couple of days, restoring sexual function for that period. Adding Wellbutrin to an SSRI is another way to restore libido. But not all doctors may try these adjustments; they may just say that's the price you have to pay."
Another fly in the psychiatric salve is that that these drugs have been officially approved only for short-term use—six to 12 months—yet are routinely prescribed for indefinite periods, in order to prevent future depressive episodes. It's not that the drugs are contraindicated for long-term use, it's just been impossible to conduct long-term studies. Americans move or drop out.
"So you have this disparity between the length of time for which the medications are approved and the length of time you might have to take them in order to have a good interval without depression," says Peter D. Kramer, M.D. "No one has really bridged that gap and figured out just what is appropriate for long-term treatment. It does seem that recurrences are prevented. On the other hand, do the medications lose their effectiveness? Are there long-term side effects? These are just not known."
What is known is that although many individual depressive episodes can be temporarily "fixed" by antidepressants, the drugs are not curative, no more than insulin cures diabetes or anti-hypertensives cure high blood pressure. The demon almost always returns at some point.
"We're increasingly recognizing something our European colleagues, who've been able to do longitudinal studies on depression, have known for some time: That major depression is predominantly a recurrent illness," says Fred Goodwin, M.D., professor of psychiatry at George Washington University, former director of the National Institute of Mental Health, and host of "The Infinite Mind" on National Public Radio. "Eighty percent of people who have had one episode will eventually have another one, one year or many years down the road."
So why not just stop the medication after one episode is cured and wait until the next one hits before resuming treatment? Kramer points to a phenomenon known as kindling: the more episodes you have, the worse they get—and the less stress it takes to trigger them. Anecdotal evidence also suggests that going on and off medications may increase the dose needed next time to achieve the same benefit as last time. In the long run, stopping and starting doesn't reduce overall drug exposure.
Untreated, some depressive episodes eventually resolve themselves, on average, says Goodwin, in less than a year, though there is considerable variation from person to person. What antidepressants do is speed recovery by eliminating symptoms and enhancing motivation and energy.
Klein points out that of 100 depressed patients given any antidepressant, only 66 will show improvement. However, half of these positive responses are a placebo effect. Thus, only a third of patients are truly responding to the specific drug.
In Klein's estimation, the vast majority of sufferers—85% to 90%—can find substantial relief with one or a combination of drugs within six to eight weeks, assuming they faithfully follow the prescribed drug regimen ("total compliance" in medical jargon). Most people with depression, he says, can find relief with the first or second antidepressant they try. Only about 10% to 15% of patients, unipolar and bipolar, are truly resistant to treatment.
A study of 161 outpatients, reported in the Journal of the American Medical Association, demonstrated that long-term treatment with sertraline (Zoloft) prevents recurrence of chronic severe depression. In the study, conducted for 76 weeks, 50% (42) of 84 placebo-treated patients experienced recurrence of significant depressive symptoms, versus only 26% (20) of 77 patients given sertraline.
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chronic illness,
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donald klein,
downside,
indefinite periods,
new york state psychiatric institute,
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serotonin reuptake inhibitors,
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sexual function,
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