Chronically Depressed? What to Do When Antidepressants Don't Work

The range of options includes cognitive behavioral therapy and brain stimulation techniques like ECT.

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Last winter, confined to bed by intense sadness, exhaustion, and headaches, the University of Kansas student found herself considering suicide. Desperate after a years-long struggle with depression, she sought a treatment she had once viewed as extreme: electroconvulsive therapy. After a few sessions, "I literally went from almost unable to function—feeling suicidal—to a 180-degree change," she says.

The student, who still contends with depression, is one of the many people chronically in its grip who, disappointed by antidepressants, are finding some relief in therapies ranging from exercise to various forms of high-tech brain stimulation. Some 27 million Americans were taking an antidepressant in 2005, more than twice the number almost 10 years earlier, thanks largely to the arrival of Prozac and other effective antidepressants with fewer side effects. But a groundbreaking 2006 trial known as STAR*D revealed that about one third of people found total relief with their first drug, and around a third were not helped even after trying several drugs and combinations. ECT, which has been controversial since the days when it was performed without anesthesia and sometimes without proper consent, has evolved considerably in recent years; by inducing a seizure, it is thought to reset dysfunctional brain circuitry. It "is the most effective and rapidly acting treatment for severe depression," says Sarah Lisanby, a professor of clinical psychiatry at Columbia University Medical Center who is a leading brain stimulation researcher.

Because ECT is an invasive therapy that involves anesthesia and often memory loss, people suffering from unrelenting depression are steered to other approaches first. These might include continued medication—though getting a response can take considerable work. Steven Hollon, professor of psychology and a depression researcher at Vanderbilt University, is concerned that family practitioners, who have become much more comfortable writing prescriptions for the newer antidepressants, don't offer enough follow-up. It can take six weeks for an antidepressant to kick in; many people simply give up, especially if the new drug comes with, say, headaches or an upset stomach. "That can be asking a lot of a person," says Matthew Rudorfer, psychiatrist and associate director for treatment research at the National Institute of Mental Health. It may well be, he says, that side effects would subside, or that switching drugs or adding a second one can work.

[Brain Stimulation: Can It Help You?]

Add therapy? Or perhaps a dose of therapy is called for. An August report in Archives of General Psychiatry revealed that people on antidepressants are less likely to also be in therapy than they once were—about 20 percent in 2005, down from nearly 32 percent in 1996. But some evidence suggests that chronic depression may respond more readily to medication plus therapy than to either alone. And one arm of the STAR*D trial showed that turning to cognitive behavioral therapy after a first drug fails works about as well as trying a second medication.

This particular brand of talk therapy doesn't take a Freudian look back into your childhood. Rather, it focuses tightly on correcting the negative or catastrophic thought patterns ("I'm such a failure," "I'm not worthy of being loved") that so often stoke depression. The concept is supported by an increasingly robust body of research. Moreover, some intriguing work in neuro imaging has shown that CBT "not only works to relieve symptoms but is also associated with brain function changes," says Madhukar Trivedi, a lead researcher on STAR*D and a professor of psychiatry at University of Texas Southwestern Medical School.

Clearly, the way we think matters. "In a depressed person's mind, thoughts tend to be overly pessimistic, overly harsh in regard to how the world works," explains Robert DeRubeis, a psychologist and a depression and CBT researcher at the University of Pennsylvania. "Our behaviors follow from the judgments we make" and often just deepen feelings of woe. A depressed person may decide not to attend a party, for example, because he believes no one will talk to him. But with a therapist's probing, he might examine how realistic that belief is and realize he has the power to start the conversational ball rolling. Some research suggests CBT may have a more lasting effect than antidepressants after treatment ends, perhaps because people have mastered the strategies that keep them from getting depressed, says Hollon.