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Still, a new generation of medications--perhaps tailored to particular serotonin receptors--is urgently needed for the 20% of depressed patients who do not benefit from existing drugs. Researchers hope to come up with compounds that begin acting immediately rather than in a period of weeks. "The Holy Grail of new antidepressant treatment is rapid onset," asserts Dr. John Ascher, a research physician at Glaxo Wellcome in Research Triangle Park, North Carolina. "We're talking about medicine that takes effect in just a day or two."
Ultimately, scientists would like to figure out how genetic defects cause depression, and then to design drugs to correct whatever has gone awry. Gene mapping would be particularly helpful to people at risk for manic-depressive illness: although lithium and related drugs usually relieve the manic episodes, current antidepressants are often ineffective against the acute depressive ones. Says Ascher: "That's the real frontier."
Obsessive-compulsive disorder, which affects 1% to 3% of Americans, was until recently considered a chronic, untreatable condition. Victims more ordinary than Lady Macbeth and Howard Hughes are haunted by persistent, intrusive thoughts or worries (obsessions), and may spend countless hours performing repetitive rituals (compulsions) such as hand washing, counting, hoarding old clothes, arranging napkins in a meaningless symmetry or checking a hundred times to make sure the electric coffeemaker is turned off. Themes of dirt, contamination or germs rule their thoughts, and other common obsessions center on horrific or violent images, a need for symmetry or exactness, or an exaggerated sense of sin or morality.
A key breakthrough in OCD treatment came about in the late 1980s, when researchers discovered that a particular antidepressant, clomipramine hydrochloride (brand name: Anafranil), relieved obsessions and compulsions as no others did. The presumed secret of its success was its ability to inhibit the reabsorption of serotonin in the brain. A few years later, the advent of the ssri family made it even more obvious that obsessive-compulsive disorder was at least in part a serotonin problem. Some 75% to 80% of ocd patients today get substantial relief--sometimes complete remission--from one or another member of the SSRIS.
Recently, positron-emission tomography (PET) scan studies at the UCLA School of Medicine have revealed that either Prozac or cognitive therapy can actually restore normal function in the obsessive-compulsive brain. The scans have documented that ocd patients have abnormal activity in the head of the caudate nucleus, a part of the brain's deep-dwelling basal ganglia, coupled with unusual activity in the orbital prefrontal cortex, just above the eye sockets. The caudate nucleus normally acts as a gatekeeper, determining which thoughts, feelings and behaviors take priority. When it malfunctions, the "worry inputs" generated in the orbital prefrontal region run unchecked, and irrational beliefs become rigid and intractable.