Men & Depression: Facing Darkness

Depression-screening tests are so effective at early detection and may prevent so many future problems (and expenses) that the U.S. Army is rolling out a new, enhanced screening program for soldiers returning from Iraq. College health-center Web sites nationwide provide the service to their students, and even the San Francisco Giants organization offers these tests to its employees.

At Clark University in Massachusetts, where Sigmund Freud introduced his theories to America, researchers are developing new clinical strategies to encourage men to seek help. The Men's Coping Project, led by Michael Addis, recruits men for interviews and discussion groups that focus not on depression but on how they deal with "the stresses of living." At a recent staff meeting, the team reviewed the file of a middle-aged local man who described himself as stressed, angry and isolated, but vehemently denied that he was depressed. In a questionnaire, the man indicated that he preferred "to just suck it up" rather than dwell on his problems and that he believed part of being a man was "being in control." Researchers decided that rather than say "you have a problem" or "you need help," they would praise his self-reliance and emotional discipline, and suggest that meeting with a counselor might be the most effective way for him to "take charge of the situation." So far, Addis and his team have met with 50 men, some of whom said they would seek counseling, and they plan to interview another 50 before the program concludes next year.

For decades, scientists believed the main cause of depression was low levels of the neurotransmitters serotonin and norepinephrine. Newer research, however, focuses on the nerve cells themselves and how the brain's circuitry can be permanently damaged by hyperactive stress responses, brought on by genetic predisposition, prolonged exposure to stress or even a single traumatic event. "When the stress responses are stuck in the 'on' position, that has a negative effect on mood regulation overall," says Dr. Michael C. Miller, editor of the Harvard Mental Health Letter. A depressed brain is not necessarily underproducing something, says Dr. Thomas Insel, head of the National Institute of Mental Health—it's doing too much.

These discoveries have opened up broad new possibilities for treatment. Instead of focusing on boosting neurotransmitters (the function of antidepressants in the popular SSRI category such as Prozac and Zoloft), scientists are developing medications that block the production of excess stress chemicals, hoping to reduce damage to otherwise healthy nerve cells. They are also looking at hormones. In a recent study, DHEA, an over-the-counter hormonal therapy, was shown to be effective in treating major and minor midlife-onset depression. And Canadian scientists have had success with deep brain stimulation—a procedure in which two thin electrodes are implanted in the brain to send a continuous electrical current to Area 25, a tiny, almond-shaped node thought to play a role in controlling emotions. In recent trials involving patients who got no relief from other forms of treatment, all the subjects reported mood improvements within six months and, remarkably, most said they were completely cured of depression.

Researchers at the NIMH are also experimenting with the idea of fast-acting antidepressants that would relieve symptoms in a few hours instead of the eight weeks or more needed for most antidepressants to take effect. In clinical trials, scientists found that a single, IV-administered dose of ketamine, an animal tranquilizer, reduced the symptoms of depression in just two to three hours and had long-lasting effects. Because of its hallucinogenic side effects, ketamine can never be used out of controlled environments. But the success of the trial is giving scientists new ideas about drugs and methods of administering them.

The most effective remedy remains a combination of medication and therapy, but finding the right drug and dosage is still more art than science. The nation's largest depression-treatment study, STAR*D, a three-year NIMH-funded project, found that 67 percent of patients who complete from one to four treatment steps, such as trying a different medication or seeking counseling, can reach remission. The process can be onerous and frustrating, and the potential side effects, including a low libido, can be hard to take—especially for men. Stephen Akinduro, 35, an unemployed phone operator in Georgia whose mother had committed suicide, tried two different drugs over a three-year period, but both resulted in weight gain, fatigue and a diminished sexual performance. "When that happened I was, like, 'What is going on here?' " says Akinduro. Frustrated, he gave up on antidepressants. Today he gets free counseling through his church and a local support group. Twelve years after his diagnosis, he is still struggling.