An Absence of Alice

Sex differencesin psychoactive drug response

By PT Staff, published on November 01, 1994

Funny thing. Women are twice as likely to be depressed as men and get 83 percent of antidepressant prescriptions. Yet current dosing recommendations are based on studies of men.

Jean Hamilton, M.D., of Duke University, has more than theoretical grounds for worry. Over a decade ago, while working at the National Institute of Mental Health, she found that normal variations in the menstrual cycle affected women's response to widely used psychotropic drugs, such as lithium. So did oral contraceptives. And when antianxiety drugs were given to women taking postmenopausal estrogen, they suffered seizures; what's more, estrogen was less effective against the menopausal symptoms.

An early benchmark in her research was a manic depressive whose levels of lithium plummeted before her period, making her "literally psychotic." Hamilton boosted the dose premenstrually, then returned it to normal--the two-step dosing worked well.

Hamilton also uncovered some antidepressants and anticonvulsants, used for certain hard-to-treat depressions, that showed menstrual variations. "A two-tiered dosing regimen was helpful in more and more women as we began to look at it," says Hamilton. "It can be the difference between being hospitalized or being suicidal or not." She has also explored gender differences in the side effects of neuroleptics, drugs to combat schizophrenia, and found that women should be receiving lower doses than men, on whom they were originally tested.

What concerns her most now, though, are over-the-counter diet pills. Though 90 to 95 percent of users are women--get this--initial studies proved they were safe in young men. Hamilton sees this as a huge oversight, since earlier animal studies suggested the pills may give women high blood pressure, even stroke, especially if they are also using oral contraceptives.

She thinks there's good reason to study sex difference in psychoactive drug response.