Study finds that costly new antipsychotics offer few benefits over traditional drugs

The results of a major 18 month study indicate that four new drugs used to treat schizophrenia offer few, if any, benefits over much less expensive older medicines.

The study has been described as “the largest, longest, and most comprehensive independent trial ever done to examine existing therapies for this disease” by Thomas Insel, director of the US National Institute of Mental Health, which funded the research.

In the study 1493 patients from a wide variety of treatment settings at 57 sites in the United States were randomly assigned to one of five drugs, four of which were relatively new—risperidone, quetiapine, ziprasidone, and olanzapine—and one of which, perphenazine, was developed more than 40 years ago. The findings were published last week in the New England Journal of Medicine (2005;353:1209-23).

The findings show that all the drugs helped to control symptoms of schizophrenia, but 74% of participants stopped taking their drug because of discomfort or specific side effects, such as involuntary movements, jerkiness, tremors, or akathisia.

Patients who were given olanzapine were less likely to be hospitalised for a psychotic relapse and tended to stay longer on the treatment. However, they experienced more weight gain and metabolic changes associated with a higher risk of diabetes than patients taking the other drugs.

In the doses used in the study a month's supply of perphenazine costs about $60 (£34; £50), while the monthly costs for the newer drugs are $520 for olanzapine (Zyprexa), $450 for quetiapine (Seroquel), $250 for risperidone (Risperdal), and $290 for ziprasidone (Geodon).

The newer antipsychotics that drug makers introduced in the 1990s allegedly cause fewer neurological side effects. Intense promotional efforts have led to the drugs capturing 90% of the national market in the US, equivalent to some $10bn, said IMS Health, a global corporation that provides pharmaceutical market intelligence. The National Center for Policy Analysis estimates that Medicaid programmes spend at least $3bn a year on antipsychotics, more than for any other class of drugs.

Jeffrey Lieberman, the trial's principal investigator and chairman of the Department of Psychiatry at Columbia University and director of the New York State Psychiatric Institute, said, “The message is the glass is half full. The drugs work but they are not satisfactory to many patients, and three quarters of the people in our study voted with their feet and discontinued the drugs.”

The National Institute of Mental Health concluded, “Future reports will address a multitude of topics (eg cost effectiveness of the medications, quality of life, predictors of response) and will provide a more detailed picture of the interaction between patient characteristics, medication, and outcomes. The information from the study will inform new approaches for improving outcomes in schizophrenia.”

An editorial in the New York Times (21 Sep, sect A: 26), entitled “Comparing schizophrenia drugs,” said that the government should sponsor further similar studies. It concluded, “Surely it would be cost-effective for the government to sponsor large studies comparing a slew of expensive drugs with their cheaper alternatives.”