Introduction: Comorbidity of substance abuse and schizophrenia spectrum disorders is a pervasive problem whose prevalence ranges between 40% and 60%; within the schizophrenic spectrum, a higher prevalence of substance abuse is usually found in schizoaffective disorders . Despite the high lifetime prevalence rates, therapeutic interventions on such patients need to be better developed, as clinical trials schizophrenia spectrum disorders treatment usually consider the comorbid presence of substance abuse as an exclusion criterion . Recent data suggest that atypical antipsychotics and mood stabilizers may lessen substance abuse in patients with schizophrenia . The aim of this paper was to evaluate, as a primary outcome, the efficacy and safety of aripiprazole and topiramate combination on clinical symptomatology in a sample of opioid-dependent patients with schizoaffective disorder in methadone maintenance therapy (MMT) and, furtherly, as a secondary outcome, to test the rapid tapering of patients from methadone. Methods: Twenty patients (10 males/10 females), who met DSM-IV criteria for opioid-dependence and schizoaffective disorder, all on MMT at the dosage of 80 mg/day, received aripiprazole (10 mg/day) plus topiramate (200 mg/day) for 8 weeks. Regarding the tapering of methadone, a dose reduction of 3 mg/day to suspension at week 4 was established. Clinical symptomatology was assessed using the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS), the Hamilton Rating Scale For Depression (HDRS), and the Hamilton Rating Scale for Anxiety (HAM-A). Adverse effects and withdrawal symptoms were assessed by using the Dosage Record Treatment Emergent Symptom Scale (DOTES). The within-group differences in efficacy ratings between baseline and final test were analysed by the Wilcoxon rank sum test. The significance level for the test was p<0.05. Results: The results demonstrated that the combination of aripiprazole and topiramate was effective in reducing schizoaffective symptoms, mood and anxiety symptoms, and overall clinical symptomatology, also promoting the rapid tapering off of methadone maintenance. The combination aripiprazoletopiramate was generally well-tolerated; the most common side effects were agitation (n = 8, 40%), insomnia (n = 10, 50%), sweating (n = 8, 40%), nausea/vomiting (n = 10, 50%), diarrhoea (n = 2, 10%). These effects were generally mild/moderate and transient. Conclusions: This study indicates that combining topiramate and aripiprazole in schizoaffective opioid dependent subjects was safe and effective in treating schizoaffective symptoms and in facilitating methadone tapering-off. Despite a strong evidence base for the benefits of long-term MMT, including protection from illicit opioid use, failure of the detoxification program, and longterm relapse, indefinite MMT implies concerns about the ethics, necessity and expenses. In patients with a dual diagnosis who may be using opioids or methadone to medicate a psychiatric disorder, the likelihood that MMT may persist indefinitely is very high.
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