High-dose clozapine and high-dose olanzapine appear to have similar efficacy for patients with treatment-resistant schizophrenia, according to an article in the January 23 issue of the Journal of Clinical Psychiatry.

Herbert Meltzer, MD, director of the Schizophrenia Program in the Department of Psychiatry, Vanderbilt University, and colleagues have shown that the success of clozapine in treating patients with treatment-resistant schizophrenia was not due to unique pharmacologic features of the drug itself, but the fact that it was used at higher doses than is used to treat patients with schizophrenia who respond well to antipsychotic drugs. Clozapine is rarely used for the 70 percent of patients whose psychotic symptoms respond well to a wide array of other antipsychotic drugs.

The study included 40 men and women, ages 18 to 58 years, diagnosed with schizophrenia or schizoaffective disorder. Patients were recruited from three U.S. outpatient community mental health treatment facilities, including Nashville's Centerstone Mental Health Center. The double-blind trial randomized patients to olanzapine (mean dose, 34 mg/day; 19 patients) or clozapine (mean dose, 564 mg/day; 21 patients).

Olanzapine, whose pharmacology is considered closer to clozapine than that of any other drug available was as effective as clozapine in improving psychopathology and cognition in these treatment-resistant patients. The study showed that patients taking higher doses responded more slowly than average patients taking conventional doses. In fact, both drugs needed to be given for six months before a good treatment response occurred, compared with six weeks for the average patient at the lower dose range.

"The results provide another option for treatment of those patients," Meltzer said.
He added, "Because of the risk and hassle, clozapine was never as widely used as it should have been. Instead of 30 percent of patients (those who are treatment-resistant) taking the drug, at most, 5 to 10 percent did."

A side effect of both clozapine and olanzapine is weight gain. "Both of these drugs very often produce serious weight gain, sometimes as much as 50 to 100 pounds," Meltzer said. Patients in this study taking olanzapine gained significantly more weight (16 pounds) than those on clozapine (3 pounds).

"This study shows that olanzapine is a viable option for those truly treatment-resistant patients who won't or can't take clozapine, providing you take the dose up to the range we used, which was three to four times the dose now established as the optimal effective dose, and if you take caution to limit the weight gain, which unfortunately may not always be successful," Meltzer said.

He cautioned that a larger study is needed to confirm his findings that the two drugs are essentially equally effective in treating this group of difficult-to-treat patients.