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Study provides doctors with method to determine most effective drug doses

IOWA CITY, Iowa -- While most people believe that more is better, a University of Iowa psychiatrist offers proof that it is not always true.

Taking more of a medication that didn't work the first time is often common practice, both among physicians and self-medicators. However, a study by Dr. William Coryell, UI professor of psychiatry, may lead psychiatrists to reconsider how they prescribe drugs for schizophrenia and other mental illnesses.

The study, published in the January 1998 issue of the American Journal of Psychiatry, revealed that increasing a commonly used medication for patients with schizophrenia when the initial dosage is ineffective may not be the best way to go.

Coryell studied the effects that different doses of haloperidol, an antipsychotic medication marketed as Haldol, had on schizophrenic patients. He found that a patient's plasma level may enable doctors to determine if an increased or decreased dose would be more effective in easing symptoms. According to Coryell, the study findings can help guide doctors toward getting better results when prescribing drugs. It provides a way of determining the best dose for each patient.

By looking at the various plasma levels of 66 schizophrenic patients and comparing the drug's effectiveness on each patient, Coryell determined that haloperidol could be more effective for certain patients when administered in smaller doses rather than a larger one.

Haloperidol is one of the most commonly prescribed conventional drugs for schizophrenia and works to relieve the "positive" symptoms of the disease, such as hallucinations and delusions. Newer, atypical antipsychotic drugs have been developed to improve schizophrenia's "negative" symptoms, which include blunted affect, lack of drive and lack of sociability.

Typically, when the first prescription dose of haloperidol does not improve a schizophrenic patient's condition, doctors respond by increasing the dosage. If the higher dose does not produce better results, the doctor has to look for an alternative treatment. The key, according to Coryell, is to make the drug more effective the first time by finding out specifically what dosage will be most beneficial while causing the fewest side effects.

"The idea is that if you exceed a certain blood plasma level it may increase the side effects of the drug but not the benefits," Coryell says.

The side effects of haloperidol and other antipsychotics are drowsiness and movement disorders, usually stiffness and tremors, and a lack of facial expression.

To test the theory that plasma levels can determine an optimal dose, Coryell gave the 66 patients fixed doses of haloperidol and watched for decreases in symptoms. A simple blood test was done to determine each patient's plasma levels. The patients with higher plasma levels showed less improvement after taking the haloperidol. These patients who experienced less improvement were randomly reassigned to one of two groups. One was given a higher dose, the other a lower dose of the drug. Those whose dosages were lowered experienced significantly more improvement than those whose dosages were increased.

"The high plasma levels may be interfering with the benefits of the drug," Coryell says.

If the plasma levels of patients seeking drug therapy is determined, doctors have a better chance of prescribing the best dose the first time. This could save patients time and money, and more importantly, deliver relief faster.

3/13/98