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irony is that Prozac became popular precisely because it was nontoxic and easy to use, which is why
so many primary care physicians prescribe it. More recently it has been claimed that long-term use of
Prozac causes neurologic toxicity, and it remains to be seen if this is another myth that will be
dispelled. Over twenty other FDA-approved antidepressant medications are also available. These
prescription medications vary in their possible side effects, and require medical monitoring.

St. John's Wort and SAM-E

What about hypericum, otherwise known as St. John's wort? Many patients are already taking this
agent when they first come to our depression clinic (I codirect both the Memory Disorders Center
and the Late Life Depression Clinic at our hospital). Some people report minimal to mild
improvement on St. John's wort, and others report no change whatsoever in their depression. The
National Institute of Mental Health is now supporting a large-scale clinical trial to find out if St.
John's wort really works. Another substance called S-adenosyl methionine (SAM-E) is also gaining
popularity, but clinical studies with this substance have been very limited. More information from
systematic studies is needed before I can recommend these alternative medications as treatments for
depression.

Psychotherapy

Psychotherapy can be useful in the treatment of milder forms of depression. Cognitive-behavioral
and interpersonal psychotherapy, which require the therapist to be very active compared to
traditional psychoanalysis, have been shown to be effective in the treatment of mild to moderate
depressive illness. Highly motivated patients show the greatest benefit from these forms of therapy—
for example, cognitive therapy requires patients to do homework exercises to help correct their
negative, distorted attitudes about themselves and other people. A recent pharmaceutical industry-
supported study by Keller and his colleagues suggested a synergistic effect from combining the
antidepressant nefazodone (Serzone) and cognitive-behavioral psychotherapy, but these results are
not consistent with the prior literature on combining antidepressant medications and psychotherapy.