For example, practice guidelines from the American Psychiatric Assn. suggest that people with atypical depression -- who might oversleep and overeat instead of staying up at night and losing weight -- tend to do better with SSRIs or MAO inhibitors than with tricyclics. People who have obsessive-compulsive symptoms in addition to depression may benefit from a drug used to treat both conditions, such as an SSRI. The best treatment for people with symptoms of psychosis and depression is a combination of antipsychotics and antidepressants.
Although these suggestions may help steer doctors in the right direction, Dr. Maurizio Fava, a professor of psychiatry at Harvard Medical School, cautioned against reading too much into the few studies that match subtypes to specific drugs.
"At this point, many of the treatment recommendations are oversimplifications," he said.
About 60% of patients get at least some benefit from the first drug they try, with half of those recovering fully. Doctors can add a second treatment or switch to a new one if the first drug doesn't work. The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, a large study funded by the National Institute of Mental Health that was published in 2006, confirmed that a second drug from the same class is just as likely to work as one from a different class. That is, people who don't respond to one SSRI have just as good a chance of responding to a second SSRI as to an SNRI or Wellbutrin.
Although patients become less likely to respond with each new cycle, a significant number still do. STAR*D, which looked at drugs and psychotherapy, found that 37% of patients went into remission after the first round of treatment, 31% after the second, 14% after the third, and 13% after the fourth. A third of patients in the study continued to struggle with depression after four cycles of treatment.
Compounding the problem of finding the right drug is the fact that antidepressants take so long to work. Many people, accustomed to speedy results from drugs such as aspirin, stop taking their antidepressant if they don't feel better after a week or two. STAR*D showed that it can take as long as eight weeks for a drug to begin working and up to 12 weeks to get the full effect. Doctors don't know why the drugs take so long to work; one theory is that the increase in neurotransmitters allows neurons to adapt, grow and establish new connections over time.
Friedman said that one of the most common reasons patients get incorrectly labeled "treatment-resistant" is that they haven't taken the drug for long enough or in a high-enough dose.
But waiting can be difficult for someone suffering from intense despair. As the weeks and months tick by, people with depression may be struggling with simple tasks like paying bills or getting dressed. Jobs are lost; marriages are strained. Some people kill themselves.
People who don't respond well enough to drugs and counseling still have treatment options.
One is electroshock therapy, which works well but can cause temporary memory loss. A newer alternative, called transcranial magnetic stimulation, doesn't affect memory but may be less effective. This is the treatment that Porter turned to after his long struggle with depression. He said that he was feeling much better after a month of daily treatments five days a week at UCLA.
"The critical thing for patients is not to get demoralized and give up," said Fava.