Schizophrenia is notoriously difficult to treat, but a new study out this week in the New England Journal of Medicine could help patients and their doctors sort out the best medications. Yet the study raises nearly as many questions as it answers and the biggest finding may be how much room we have left for improvement in treating the millions who suffer from this debilitating mental illness.

The 18-month nationwide study of nearly 1,500 schizophrenia patients pitted five different antipsychotic medications, one old and four new, against one another. By the end of the study, about three fourths of the patients had either quit taking their medication or switched to a different one because they felt it wasn't helping or because the side effects were too much to handle.

"It's humbling and very important to realize that we don't yet consistently have a medication that is something people want to take," says Ken Duckworth, a psychiatrist and medical director of the National Alliance on Mental Illness who was not involved with the study.

More patients, 36 percent, stayed on a brand-name drug called Zyprexa until the end of the study than any other. People on the other drugs discontinued at about the same rates. Perphenazine, an older, generic drug, did about as well as any of the others, which surprised some given that it is older and considerably much less expensive than the newer drugs.

Zyprexa, currently the top-selling of these drugs, has fallen out of favor recently because patients sometimes gain weight and can develop Type 2 diabetes. In this study, 30 percent of the patients taking Zyprexa gained 7 percent of their body weight or more over the course of the study. On the other hand, perphenazine and other some of the other medications are less likely to cause weight gain but have been associated with muscular side effects similar to those seen in Parkinson's disease.

The bottom line of this study is that doctors will still have a hard time deciding what to give their schizophrenia patients.

"The patient with schizophrenia and his or her doctor face difficult choices," writes Robert Freedman, a psychiatrist at the University of Colorado Health Sciences Center in an accompanying editorial. The drugs that are the most effective, Zyprexa and clozapine (not included in the study), also have the highest rate of side effects, he points out.

In addition, people with schizophrenia can vary widely in their symptoms and in how heavily they react to each medicine. Individual patients, for unknown reasons, will respond better or worse to different drugs.

"There remains no simple answer for what to prescribe patients with schizophrenia," Duckworth says.