title: Clozapine for comorbid substance use disorder and schizophrenia: do patients with schizophrenia have a reward-deficiency syndrome that can be ameliorated by clozapine?
abstract: Alcohol and other drugs of abuse are commonly used by persons with schizophrenia and contribute to the overall morbidity of the disorder. Standard, or typical, antipsychotic drugs do not limit such substance use and may even render it more likely. However, preliminary data from our group and others suggest that the atypical antipsychotic clozapine may decrease substance use in this population. While recognizing the likelihood that substance use decreases negative symptoms (as well as extrapyramidal symptoms) in persons with schizophrenia, we hypothesize that the biological basis of substance use relates to a "reward-deficiency syndrome" secondary to dysfunctional dopamine-mediated mesocorticolimbic neurons in these individuals. We further suggest that clozapine's beneficial effect in patients with comorbid schizophrenia and substance use disorders may relate to its presumed ability to ameliorate the deficits in both the mesocortical and mesolimbic dopaminergic neuronal projections through its various actions on dopaminergic, serotonergic, and particularly noradrenergic neurons.
authors.affiliation: Commonwealth Research Center, Massachusetts Mental Health Center, Boston 02115, USA.
authors.forename: A I
authors.initials: AI
authors.lastname: Green
authors.forename: S V
authors.initials: SV
authors.lastname: Zimmet
authors.forename: R D
authors.initials: RD
authors.lastname: Strous
authors.forename: J J
authors.initials: JJ
authors.lastname: Schildkraut
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003024:Clozapine / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008032:Limbic System / Q000187:drug effects; D009434:Neural Pathways / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects; D011941:Receptors, Adrenergic / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects; D012201:Reward; D012559:Schizophrenia / Q000150:complications* / Q000188:drug therapy*; D012651:Self Medication / Q000523:psychology; D019966:Substance-Related Disorders / Q000150:complications*; D013577:Syndrome; D017557:Ventral Tegmental Area / Q000187:drug effects
chemical_list: D014150:Antipsychotic Agents; D011941:Receptors, Adrenergic; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D003024:Clozapine