/publications/gpr/2006/GPR_2006-02/GPR_2006-02_3432

GENERIC SCHIZOPHRENIA DRUG PASSES TEST

Author: Eileen Koutnik-Fotopoulos, Staff Writer

Can a generic schizophrenia medicine from the 1950s be in the same league as the newer antipsychotic drugs? A $67-million federally funded study found that, overall, the medications were comparably effective. "When we first started the study, we chose a first-generation drug because we wanted to give it [the drug] an optimal chance,"said Scott Stroup, MD, MPH, coprincipal investigator of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study.

Dr. Stroup said that the significant differences in the CATIE study were that it was the longest and largest study (January 2001 to December 2004) to look at schizophrenia drug treatment in real-world settings, and that it was conducted independently. The National Institute of Mental Health (NIMH), which funded the investigation, pushed for an independent analysis, because the studies that are conducted by pharmaceutical companies to get approval for their medicines are not modeled to compare them with other available treatments. These studies also do not shed light on the conflicting claims about the risks and benefits of new drugs, compared with each other and with older drugs.

The study's 1432 patients with schizophrenia were recruited at 57 clinical sites in the United States, including university clinics, state mental health agencies, Veterans Affairs medical centers, and nonprofit agencies. At the study's onset, the patients were randomly assigned to receive 1 of 5 medications for 18 months: the older antipsychotic perphenazine, olanzapine (Zyprexa, Eli Lilly), quetiapine (Seroquel, AstraZeneca), risperidone (Risperdal, Janssen), and ziprasidone (Geodon, Pfizer).

Reporting in the New England Journal of Medicine (September 22, 2005), the investigators found that nearly 75% of the participants discontinued their assigned medications in <18 months. The percentages of patients that discontinued each drug were as follows: 75% for perphenazine, 64% for olanzapine, 82% for quetiapine, 74% for risperidone, and 79% for ziprasidone. The patients cited inefficacy, intolerable side effects, or other reasons for stopping their medications. Dr. Stroup noted that these patients switched to another drug in the study. (In clinical settings, it is not unusual for patients to discontinue one drug and begin taking another.)

"It is very hard to find a medicine to treat schizophrenia. There are a lot of individual differences in how people react to drugs. Patients who take medicines are far less likely to relapse,"noted Dr. Stroup.

The results of the study showed that patients who started on olanzapine were less likely to be hospitalized for a psychotic relapse and tended to remain on the medication longer, compared with patients taking the other drugs. Olanzapine did cause patients to gain significantly more weight, however, and to experience more metabolic changes linked with an increased risk of diabetes, than did the other drugs.

One reason physicians may have resisted prescribing older drugs is the long-standing fear about movement side effects (rigidity, stiff movements, tremor, and muscle restlessness) associated with them. This was not the case in the CATIE study, however. Movement side effects actually were seen less frequently with perphenazine than with the newer drugs.

The researchers concluded that the newer medications have no substantial advantage over perphenazine. The findings are significant, considering that perphenazine costs only about $50 a month, compared with hundreds of dollars for the newer drugs, depending on the dose, said Thomas Insel, MD, director of the NIMH. The second-generation antipsychotics comprise 90% of today's market and reached $10.1 billion in US sales last year, according to IMS Health.

What do the findings mean for physicians who treat the 3.2 million patients with schizophrenia? Dr. Stroup suggested that physicians should "consider first-generation drugs along with second-generation drugs when looking at treatment for patients."

Future phases of the study will explore a range of topics (eg, cost-effectiveness of the medications, quality of life, predictors of response) and will provide a more comprehensive picture of the interactions between patient characteristics, medication, and outcomes.