Dr. Schooler opened by saying that the most widely studied and clinically important risk factor complicating treatment for schizophrenia is substance abuse. The lifetime incidence of substance abuse in persons with schizophrenia is 47%, according to the Epidemiological Catchment Area Study. At any point in time, the prevalence ranges from 25% to 35%. Substance abuse contributes to poor outcome in persons with schizophrenia and is associated with relapse, rehospitalization, noncompliance, and homelessness.

Dr. Schooler published a large, multicenter study that compared fluphenazine at one of three dosage levels with two forms of family treatment. The researchers found a strong association between dosage and relapse rates: relapse rates were significantly lower during treatment with higher dosages and were significantly higher during treatment with lower dosages.

Dr. Schooler's study also included data on substance abuse, based on self-report by patients. Self-reporting, according to Dr. Schooler, likely underestimates rates of substance abuse because patients are reluctant to report it.

In one part of the study, patients were retrospectively assigned to one of several groups. One group had low or no alcohol intake; another group used only alcohol or only other drugs, and another group used both alcohol and other drugs. The patients who were using both drugs and alcohol were placed in the drug use group.

Dr. Schooler noted that the drug users had more social contact than the other two groups as measured by a scale rated by nursing staff. This was attributed in part to the social contact required in obtaining and using illicit substances

Patients who used no alcohol or small amounts of alcohol had higher ratings of diminished affective expression and social amotivation; patients who either used alcohol or drugs showed less impairment in affective expression and social motivation.

Dr. Schooler pointed out that many strategies can be used for evaluation of effects of comorbid conditions: One intensively studies the group as a whole; another looks at the differences that cohort and conditions can make; a third studies outcomes in specific populations.

The change from efficacy to effectiveness as a measure of outcome in many studies will lead to inclusion of patients with disorders other than schizophrenia alone. Accordingly, Dr. Schooler believes that a cohort-and-condition approach may be best for studying schizophrenia associated with substance abuse, especially when assessing longer-term outcomes.