When determining who is a candidate for long-term drug therapy (lasting more than one year), doctors consider frequency of and length of time between episodes, severity of depressive symptoms, risk of suicide as well as family history of mood disorders. One of the most debated treatment dilemmas today is how to handle the persistent low-grade depression known as chronic dysthymia: does it merit long-term medication, or medication at all? Jesse Rosenthal, M.D., chief psychopharmacologist at Beth Israel Medical Center in New York City, suggests that the personal price paid by the chronically dysthymic can be as great as that paid by people with major depression, in terms of damaged relationships, poor work performance and overall low energy.
Still, it's not as simple as just putting everyone who is depressed on long-term drug therapy. Some patients will run into so-called "Poop-out"; the medications simply stop working after a while. There are no official data on the antidepressant poop-out rate, but experts estimate it at about 20%. According to Klein, poop-out is highly unlikely to occur before three or four months of treatment; after that, there is no saying whether or when it wilt. "Poop-out is not uncommon, but it's not the expectation" says Goodwin. "It is possible to keep taking these drugs indefinitely at the same dose and maintain the same level of relief."
Another unknown is what's behind poop-out—whether it is true pharmacologic failure or a worsening of the disease, a relapse that overrides medication. Other factors that can dent a medication's apparent effectiveness are aging (which tends to worsen or change depressive symptoms), substance abuse, a co-existing medical illness and noncompliance, a big problem.
Rajinder Judge, M.D., clinical research physician for Prozac at Eli Lilly, estimates that just 50% of patients actually take antidepressants properly. "They miss doses or just stop on their own," she says. It is not uncommon for patients to drop their medications after four months, although prevention of relapse is believed to warrant longer treatment. Some find the side effects too pesky. Others become overconfident because they feel so much better. "Once you recover," Judge explains, "you don't want to be reminded of those dark days and the only thing reminding you is this little pill."
Whatever the cause of poop-out, it can almost always be remedied by upping (or sometimes even reducing) the dose, or changing or adding medications. Whereas older medications—so-called tricyclic antidepressants and monoamine oxidase (MAO) inhibitors—can be dangerous at high doses, amounts of the SSRIs can be doubled and then doubled again without harm, according to Peter Kramer. "Sometimes the patient ends up on a more complicated regimen to get the same effect," he says. "Or sometimes it's a matter of taking a person off one drug and reintroducing it later. One way or another, it is mostly possible to get people back to where they were."
While Kramer is a proponent of antidepressants, he also expresses some skepticism, especially where dosing and long-term side effects are concerned. "My sense is that we're giving Prozac at too high a dose. Many people can do well with 10 mg, but 20 mg to 80 mg is common. Also, there's suspicion that the SSRIs may affect memory in the long run; it's hard to be sure because depression itself impairs memory."
And what role does good old-fashioned psychotherapy play these days? A mega-analysis of 595 patients with major depressive disorder, reported in the Archives of General Psychiatry, concluded that the best treatment plan involves a combination of psychotherapy and drug therapy.
But there are many kinds of therapy and not all are equally effective. Goodwin advocates a here-and-now approach of behavioral and cognitive techniques.
Furthermore, he says, even patients prescribed medication alone need psychological attention. Knowledgeable clinicians "can miss things like poor compliance, life stresses and substance abuse that can interfere with the medicine's working."
Depression, Donald Klein asserts, is among the most medically treatable illnesses. Accepting that short-term treatment may not be a possibility for most is perhaps the next hurdle to get over. "I now know that there is no cure," says Sheila Singleton. "I will have depression for the rest of my life and I'll take medication the rest of my life."
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