Clinical Textbook of Addictive Disorders 3rd ed - R. Frances, S. Miller, A. Mack (Guilford, 2005) WW

12. Co-Occurring Substance Use Disorders and Other Psychiatric Disorders 287strated little efficacy in mood or cocaine outcome measures. An open label trialwith valproate in patients with bipolar disorder and SUD (Brady, Sonne,Anton, & Ballenger, 1995) resulted in improvement in mood and substance usemeasures. Additionally, open-label trials of lamotrigine (Brown, Nejtek, Perantie,Orsulak, & Bobadilla, 2003) and quetiapine (Brown, Nejtek, Perantie, &Bobadilla, 2002) in patients with bipolar disorder and cocaine dependence suggestthat these medications may be associated with improved mood symptomsand cocaine craving, although not with significant reductions in cocaine use.Since there have been no double-blind, placebo-controlled studies assessing theefficacy of mood stabilizers or antipsychotic medications in adults with bipolardisorder and SUDs, the results of these open trials can be seen as preliminary atbest. However a double-blind, placebo-controlled, 6-week trial of lithium inadolescents with bipolar disorder and substance dependence (Geller et al.,1998) found lithium to be efficacious for outcomes in both disorders.SchizophreniaUnfortunately, the literature on the pharmacological treatment of patients withschizophrenia and SUDs is limited to retrospective or open-label prospectivestudies, some of which lack a comparison group. For example, an open trial ofdesipramine added to antipsychotic treatment in an integrated dual-diagnosisrelapse prevention program has shown promise in reducing cocaine use andimproving psychiatric symptoms (Ziedonis, Richardson, Lee, Petrakis, & Kosten,1992). Additionally, preliminary reports suggest that there may be a potentialbenefit of second-generation antipsychotic medications such as clozapine(Buckley, Thompson, Way, & Meltzer, 1994; Drake et al., 2000; Zimmet,Strous, Burgess, Kohnstamm, & Green, 2000), olanzapine (Littrell, Petty,Hilligoss, Peabody, & Johnson, 2001), and risperidone (Smelson, Losonczy,Davis, et al., 2002) in improving substance use outcomes in populations withco-occurring schizophrenia. Clozapine has been hypothesized to be uniquelybeneficial: Its unique pharmacological receptor activity may correct underlyingreward system deficits of patients with schizophrenia and SUDs (Green,Zimmet, Strous, & Schildkraut, 1999; LeDuc & Mittleman, 1995). Additionally,when administered in low doses (50 mg or less) to normal volunteers,clozapine has been shown to attenuate the subjective high and rush associatedwith cocaine, as well as its pressor effect (Farren et al., 2000).Despite these encouraging findings, there is evidence from normal studyvolunteers that low-dose clozapine may increase cocaine blood levels and causenear-syncope (Farren et al., 2000). However, to our knowledge, there are nocase reports or studies documenting clinically significant syncopal episodes inpatients with schizophrenia and stimulant use disorders who are prescribedclozapine. Thus, while the introduction of second-generation antipsychoticsare encouraging in their potential to improve SUD outcomes in this dually