Better Living Through Chemistry

Psychiatric drugs are a tricky business. Finding out which chemicals affect the brain—and how—may require looking at the genes.

MONYA BAKER

“Each and every doctor I have ever visited has �diagnosed� me with a different type of depression. I am still totally clueless just what is wrong with me. I continue to feel incredibly depressed, but no one seems to be able to find the correct treatment for me.”

— Anonymous posting to an online community for people with depression

This story will sound familiar to anyone involved in mental health. While physicians may fret that patients unnecessarily medicate themselves for a mild case of the blues, no one denies the reality of bipolar disorder, depression, or schizophrenia. Yet psychiatrists often resort to hunches to find combinations of prescriptions and psychotherapies to help patients. Even then, doctors find that a drug may take weeks to work, and patients may quit treatment too early. In its literature on obsessive-compulsive disorder, the National Institute of Mental Health urges: “If one drug does not work, others should be tried.” Psychiatrists apply this advice to bipolar disorder, depression, and schizophrenia as well. Paul Hoholik is a case manager for adults with mental illness and has himself struggled with major depression and anxiety for more than a decade. He has lived through the limitations of current treatments. Some of his bipolar patients, he says, have “been on the same medication for years, and all of a sudden it just doesn�t work.”

Hoholik estimates that he�s tried more than ten different antidepressants and feels that he�s constantly choosing between the “least of the worst.” He tried Elavil, which meant constipation and an unbearably dry mouth. Effexor did not help his mood consistently, plus it made him nauseated and bloated. He still felt depressed after six weeks on Parnate, so his psychiatrist urged him to stop. When he tried Paxil, he had sexual problems and night sweats and gained 20 pounds. Prozac made him yawn, suffer sexual dysfunction, and have terrible dreams.

Experts speculate that if 100 people diagnosed with major depression all started taking, say, Prozac (Eli Lilly, fluoxetine), perhaps 50 to 60 individuals would respond. If the same 100 people took another antidepressant, say, Wellbutrin (GlaxoSmithKline, bupropion), the results would be similar, but a different set of people would start to feel better. After trying different antidepressants and augmenting medication in sequence or various combinations, clinicians would find current treatments completely incapable of helping 5 to 10 patients, and effects in the other patients might be incomplete or intolerable. The situation is similar for schizophrenia and bipolar disorder, except that fewer of the people who respond to the drugs continue taking them.

The solution is simple—if only fictional today: shortly before a first visit to the psychiatrist, a patient would submit a blood sample or cheek swab for a mental health genotype. It would show which mental illnesses a patient is most vulnerable to, and thus help a psychiatrist distinguish between an unusual manifestation of bipolar disorder, for instance, and schizophrenia. The genotype would also help predict the type and severity of side effects for various drugs; even before meeting a patient, a psychiatrist could conceive the best combination of drugs and psychotherapies. Subsequent blood samples would monitor body chemicals so a psychiatrist could adjust treatment. In short, treatment that has been based to date only on what a psychiatrist sees and hears from a patient would be supplemented by physiological measures and genetic information.