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Schizophrenia and Substance Abuse: Is There a Role for Atypical Antipsychotics?

Schizophrenia and Substance Abuse: Is There a Role for Atypical Antipsychotics?

The prevalence of substance use disorders in patients with schizophrenia is greater than the rate observed in the general population,1 with a dramatic increase since the 1970s.2

Several theories exist to explain the high rate of comorbidity. The "self-medication" hypothesis3 suggests that persons may abuse substances to treat underlying psychotic symptoms or adverse effects of medications commonly used to treat schizophrenia.4,5 Other hypotheses include the increased availability of substances of abuse, genetic predisposition, and kindling. The findings of a recent laboratory study suggest that persons with schizophrenia may experience enhanced euphoria from alcohol consumption compared with healthy controls.6

No matter what the cause, comorbid substance use disorders among patients with schizophrenia are associated with a number of clinical challenges, including an increased rate of medication noncompliance, more frequent and longer hospitalizations, a higher rate of use of crisis-oriented services, and consequently, a higher cost of care.7 Social problems associated with substance abuse in patients with schizophrenia
include legal entanglement, housing instability, unemployment, and poor money management.8

Because of the serious consequences associated with substance abuse in this population, the development of effective treatments is of utmost clinical importance. Patients with psychotic disorders may be more reluctant to participate in traditional substance abuse treatment programs and self-help groups (such as Alcoholics Anonymous), where most members do not have comorbid psychotic disorders.9 In addition, the cognitive symptoms that are associated with schizophrenia may undermine a patient's motivation and his or her ability to learn new coping strategies in psychosocial treatments. Although specialized psychosocial treatments that focus on behavioral interventions for substance abuse in patients with schizophrenia show promise,10 they require an intensive intervention by highly trained staff.

In contrast, pharmacologic treatments are generally familiar to dually diagnosed patients and require less learning than psychosocial treatments, and the dosing schedule can be readily integrated into the patient's current treatment regimen.

Pharmacologic interventions that have been evaluated (eg, the medications used to treat alcohol dependence, including disulfiram and naltrexone) seem to have clinical use in this population.11 However, these results were from small pilot studies; studies of patients with alcohol dependence and schizophrenia are under way.12,13 In short, effective pharmacotherapies to treat substance abuse in patients with schizophrenia would likely have a widespread positive clinical impact in the treatment of these disorders.

Results of the use of atypical antipsychotics in the treatment of substance use disorders in comorbid populations are promising. The first line of treatment for persons with schizophrenia
is usually an antipsychotic medication. Atypical antipsychotics (including clozapine, olanzapine, quetiapine, risperidone, ziprasidone, and aripiprazole), which have demonstrated efficacy in the treatment of schizophrenia, are referred to as "atypical" because they were originally thought to have fewer extrapyramidal adverse effects than conventional antipsychotic medications.14
It has been hypothesized that if these newer medications are superior in their effects on psychotic symptoms or have fewer adverse effects, they may concomitantly reduce comorbid substance use disorders. Another hypothesis suggests that because atypicals have a different pharmacologic profile from conventional antipsychotics and because they target receptors that may play a direct role in the etiology of substance abuse and dependence,4,5 they may be especially effective in treating substance use disorders as well as psychosis.

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