"It's a stealth side effect," observes Jerrold Rosenbaum, M.D., chief of psychiatry at Massachusetts General. "It emerges subtly over time and surprises everybody."
Physicians must consider what is tolerable in exchange for a medication's primary effects and understand that the bar has been raised. "As the cookie lady Mrs. Fields once said, 'Good enough is not good enough,'" says Dunner. "Just because a patient improves doesn't mean the treatment should be stopped."
Sometimes the problem lies with patients themselves. Often, they feel better and stop their medication, thinking it's no longer needed. "Although an individual patient might win, it's a mistake," observes Dunner. "The odds are against her."
At least as often, side effects interfere with long-term patient compliance. Therefore, clinicians must know how to manage the dosage or try to augment the antidepressant with another medication so the patient will stay on course. Psychostimulants such as Dexedrine, Ritalin and Adderall are widely used as antidepressant adjuncts, even though their primary indication is for attention deficit disorders or narcolepsy. Provigil, recently approved for the treatment of narcolepsy, is also used to boost the efficacy of antidepressants or reduce the drowsiness they cause. Thyroid hormones and natural remedies such as omega-3 fatty acids and SAM-e are also being explored.
Leading psychopharmacologists contend that antidepressant treatment can be delivered in a way that instills confidence in patients—enough to ride out early difficulties. "I try to emphasize the early side effects that might occur and how to manage them," reports Dunner. "So if a patient suffers from them, he doesn't say, 'What is all this about?'"
It's also important for patients to know that taking one pill will not instantly make them better; in fact, the drugs are not likely to begin working for three to four weeks. Treatment will then progress in eight to twelve weeks.
Some 30 percent of depressed patients do not respond to the first drug they try. If there is no improvement after a patient uses a medication at an adequate dose and for an adequate duration of time, a switch is in order. A drug with a different mechanism of action may be preferred. The trial, though, isn't lost. The patient may have lost time, but valuable information has been gained.
"We're trying to get the patient over that last little hump," says Dunner. "Granted, we can improve most patients, but can we actually get them back to normal? I think we can do this with many more patients than we used to."
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