by Mark Derewicz

(Medical Xpress)Put yourself in the shoes of a psychiatrist. You just diagnosed a person with schizophrenia, and you can prescribe any number of antipsychotic drugs, all of which can cause serious side effects. You know that older drugs, such as haloperidol, work well, but a third of all schizophrenia patients who take it suffer from Parkinsonian-like symptoms, such as tremors, involuntary spasms, and uncontrollable facial movements. You also know that those side effects are permanent in about half the people who experience them. In other words, you could be prescribed a drug that causes permanent brain damage.

So you consider prescribing a newer drug, such as clozapine, which also helps a large portion of patients. But clozapine causes severe weight gain and diabetes in many people. You check your patient's history. He smokes, as do 90 percent of people diagnosed with schizophrenia. He weighs a lot for his height. Taking clozapine will substantially increase his risk of heart disease, and the drug costs much more than haloperidol. Your patient can't afford it.

Choosing the right drug is difficult, but you have to choose one. Letting the patient go without medication is not an option; untreated schizophrenia is much worse than even the most serious side effects.

What do you do?

You know what you'd like to do: run a blood test to figure out your patient's genetic susceptibility to the permanent side effects of haloperidol. But that genetic screen doesn't exist. In fact, the genetic underpinnings of drug side effects, in general, are not well understood.

Researchers at the UNC School of Medicine are trying to change that.

Two labs headed by statistical geneticist William Valdar, PhD, and psychiatric geneticist Patrick Sullivan, MD, have developed a new statistical model that scientists can use to parse the complex genetics of side effect susceptibility.

In a paper featured in the journal Genetics, their teams describe how they've begun to strip away the mystery behind haloperidol. Their findings represent the first quantitative description of the genetic architecture of haloperidol response.

Genetic smoke screen

Excerpt from:
The genetics of drug tolerance

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