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Am J Drug Alcohol Abuse. 2003 Aug;29(3):553-66.

Relationship of clinical symptoms and substance use in schizophrenia patients on conventional versus atypical antipsychotics.

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Department of Psychiatry and Behavioral Sciences, School of Medicine, Emory University, Atlanta, Georgia 30335, USA.


A large body of research documents the high prevalence and devastating consequences of substance abuse among individuals diagnosed with schizophrenia. One prominent theory of the high rate of comorbidity between these disorders is that substance abuse in schizophrenia is an attempt to self-medicate psychiatric symptoms including negative symptoms and depression as well as side effects including extrapyramidal reactions (EPR). Consistent with this notion, novel antipsychotic medications, which have been shown to reduce negative and depressive symptoms while exhibiting a lower propensity to cause EPR, have been associated with reduced substance abuse in patients with schizophrenia. To further explore the self-medication hypothesis as it relates to the mechanism by which atypical antipsychotics reduce substance abuse, we compared schizophrenia patients with a history of substance abuse medicated with either conventional (n = 35) or atypical (n = 35) antipsychotics. Patients with schizophrenia who did not have a history of substance abuse who were on conventional (n = 23) vs. atypical antipsychotics (n = 29) were also examined. Assessments included the Positive and Negative Symptom Scale, Hamilton Rating Scale for Depression, Simpson-Angus, and Abnormal Involuntary Movement Scale. Compared with conventional medications, atypical antipsychotic drugs were associated with reduced levels of substance use (primarily alcohol). Interestingly, however, in substance-abusing patients there were no significant differences between patients on conventional vs. atypical agents with respect to positive or negative symptoms, depression, or EPR. These data suggest that theories related to self-medication of symptoms and side effects do not appear to account for the difference in rates of substance use found in schizophrenia patients on atypical vs. conventional antipsychotic medications.

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