Sex differences in the body's response to medication have long been overlooked. In fact, until the 1990s women were banned from participating in clinical trials in the U.S. Yet women are now almost twice as likely to be prescribed psychotropic medication as men, and research suggests that their different hormones, body composition and metabolism may make them more sensitive to certain drugs. Further, women are between 50 and 75 percent more likely to experience side effects. Last year the U.S. Food and Drug Administration announced the first sex-specific dosing guidelines for a psychopharmaceutical drug: the sleep medicine Ambien was discovered to be doubly potent for women. Here are a few of the medications that are known to act differently in men and women—but research is just beginning.
• Women experience greater pain relief from opioid painkillers, perhaps because estrogen, which fluctuates during menstrual cycles, modulates the pain response.
• Men are more likely to overdose on painkillers than women. But women have a harder time quitting. Once addicted, they are more likely to relapse—particularly in the middle of the menstrual cycle, when glucose in the brain is lower. Glucose is necessary for self-control.
• Multiple studies suggest that women respond better to SSRI antidepressants than men (particularly Zoloft), whereas men may have better luck with tricyclics.
• Some antidepressants are more potent for women. Women have less binding capacity in their blood, meaning their blood proteins mop up fewer foreign substances. If taken with other drugs, certain tricyclic antidepressants (such as amitriptyline) could overflow into the bloodstream, potentially causing more side effects. Further, women's stomachs are less acidic than men's, so SSRIs may be absorbed more quickly, which can increase their toxicity. Women's body fat may also trap antidepressants in the body for longer.
• Most psychotropic drugs are metabolized in the liver. Because the male body breaks down Ambien and other sleep aids faster, women typically have more of the drug in their system the next morning—creating problems when they have to be alert for work and driving.
• Women's less acidic stomachs may cause them to feel the effects of antianxiety medication faster and more powerfully, and the drugs could be more toxic to women at standard doses.
• Men's kidneys filter out drug compounds faster than women's. Women may need to wait longer before taking a second dose, especially of benzodiazepines such as Xanax.
• Benzodiazepines are designed to dissolve in lipids to cross from the bloodstream into the brain. Because women have more body fat, the drugs can linger in their system longer, potentially causing toxicity and side effects at lower doses.
• First generation, or “typical,” antipsychotics such as haloperidol seem to be more effective for managing hallucinations and delusions in women than in men, who require higher doses to improve their symptoms.
Anticonvulsants and more
• The liver enzyme CY P3A4 is especially active in young women, rendering some drugs—such as anticonvulsants—less effective. Preliminary research suggests several liver enzymes work at different speeds in men than in women, which might affect how the body responds to antidepressants, anxiolytics, painkillers and other drugs.
From animal studies to clinical trials, drugs are often tested on males only. Yet eight out of 10 drugs pulled from the market by the fda between 1997 and 2001 posed greater health risks for women than men, according to a government report. This testing bias can be unwitting or intentional—many clinical trials exclude women because their different hormones are considered a “confounding variable.” Pregnant women also typically do not take part in clinical trials for safety reasons, but mounting evidence suggests that their hormonal changes can alter the effects of certain drugs. For example, a study last year found that pregnant women with bipolar disorder require higher doses of the drug Lamictal to control their depression. In addition, medications taken only by women, such as birth-control pills, may interact with psychotropic medications with unknown consequences. The fda recently announced that it would step up its effort to account for sex differences in clinical trials.