Is it time to consider comorbid substance abuse as a new indication for antipsychotic drug development?

Comorbid drug abuse in schizophrenia has been consistently reported as high, with estimates ranging between 10-70%. Comorbid addictive states in schizophrenia are possibly multifactorial, yet recent research assigns a significant neurobiological role in its genesis. Abnormalities in hippocampal/cortical function in schizophrenia which mediate reward and reinforcement behavior are identified as central to the development and maintenance of comorbid addictive states. Preliminary data suggest that the vulnerability of patients with schizophrenia to substance use disorders may be a primary disease symptom. The management of comorbid substance abuse in schizophrenia relies on the use of antipsychotic medications. Recent data raise the concern about whether first-generation antipsychotics in long-term use can conversely lead to enhancement of the abused substance's reinforcing properties. Some recent reports have assigned a favorable outcome to clozapine and second-generation antipsychotics, pointing to a possible differential role for various antipsychotics. In view of the high prevalence of comorbid drug abuse in schizophrenia, its impact on outcome of treatment and the recent emerging neurobiological information, it is my contention that comorbid drug abuse constitutes a dimension by itself and deserves to receive an indication in the development of new antipsychotics similar to negative symptoms or cognitive deficits.