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Mental Illness: Is 1 Drug Better Than 2?

Mixing mental illness drug 'cocktails' is still more art than science.

By Daniel DeNoon
WebMD Feature

Reviewed By Michael Smith

They call them drug cocktails. They're becoming the vogue for mental illnesses such as bipolar disorder and schizophrenia. But mixing drugs is still more art than science.

If you have a serious mental illness, it's becoming more likely that you'll be treated with multiple drugs. Doctors call this polypharmacy. Polypharmacy is common for conditions such as heart disease, cancer, and HIV infection. The basic idea is to attack the mental illness on multiple fronts, using different drugs with different actions.

That's the upside. It can offer mental illness patients tremendous benefits when doctors have a careful, rational plan for trying multiple drugs. But there's a downside, too, says Andrew C. Furman, MD, director of clinical services for psychiatry at Atlanta's Grady Memorial Hospital and associate professor of psychiatry at Emory University.

"Unfortunately, in the majority of cases doctors are just throwing everything they possibly can at a mental illness in hopes that something will get better," Furman tells WebMD.

That happens too often, agrees Alan J. Gelenberg, MD, head of psychiatry at the University of Arizona and editor-in-chief of the Journal of Clinical Psychiatry.

"What often happens in busy practices, both private and public, is that medications are thrown on without adequate information," Gelenberg tells WebMD. "Patients can end up with regimens that include multiple drugs without a rationale for using them all. It is not uncommon to look at a medical chart and say, 'I can't figure out why a patient is on this combination regimen.'"

That can be bad news for mental illness patients, says Beth Murphy, MD, PhD, a psychiatric drug researcher at McLean Hospital in Belmont, Mass., and instructor in clinical psychiatry at Harvard University.

"The bad news is it costs more. And the more medicines you take, the more likely it is you will have an adverse response," Murphy tells WebMD. "Moreover, it increases the chance your medicines will [harmfully] interact with one another."

Mental Illness: Much to Learn About Drugs

When they prescribe drugs for physical diseases, doctors usually know exactly how each drug acts on the body. What is more, they have a precise idea of how this helps treat disease. Drugs for mental illness work on the brain -- by far the most complex and least understood part of the body. That makes prescribing mental illness drugs far different from prescribing drugs for heart disease, Gelenberg says.

"Definitely the increase in psychiatric polypharmacy is not coming from a better understanding of disease," Gelenberg tells WebMD. "Psychiatry isn't the same as cardiology in our understanding of the exact mechanisms of illness."

"This being the decade of the brain, there has been a burgeoning of understanding. But even with these incredible advances, the understanding of the brain is not at the same place as the understanding of the heart," Murphy tells WebMD. "We don't have enough understanding to know exactly which medicines a given individual will respond to. We have increased our understanding of the biochemistry that underlies these illnesses, but we don't know all we would like to know."

Multiple drug treatment is becoming state-of-the-art treatment for bipolar disorder, notes Mark A. Frye, MD, director of the UCLA bipolar disorder research program and associate professor of psychiatry at UCLA's David Geffen School of Medicine. But he emphasizes the word "art."

"We have little clinical trial data on which to base this, so it is still more an art than a science," Frye tells WebMD. "This is a painful contrast to other areas of medicine where doctors have large-scale clinical trial data to guide them. That is only just happening now in psychiatry."

Mental Illness: A Delicate Balance

If they don't know exactly what they are doing -- and there are no large clinical trials to guide them -- why prescribe multiple drugs for mental illness?

"This is part of a trend not to accept anything less than wellness," Murphy says. "Years ago, if a psychiatric patient was not in the hospital, that was good enough. Now, because of advances in our understanding of mental illness and mental wellness, health is the goal. So often multiple treatments are an attempt to reach that goal."

In the right patient at the right time, one mental illness drug can enhance the action of another, Frye suggests.

"There is a trend to maximize outcome, to use medications that enhance one another," he says. "We can clinically show that often when there is [enhancement], we get lower doses of both drugs and better adherence and fewer side effects."