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

26. Psychopharmacological Treatments 603apy. These patients are at risk for opiate withdrawal syndromes when prescribedmedications that induce the metabolism of opioids (e.g., inducers of cytochromeP450-3A4) and for opiate toxicity should a coadministered medicationinhibit opioid metabolism. Similarly, if an opioid delays absorption of a medicationor inhibits the metabolism of the drug; toxicity from the drug may occur.Table 26.1 summarizes drug interactions that have been shown to occur inopioid-maintained patients treated with medications for comorbid medical orpsychiatric disorders.COCAINE PHARMACOTHERAPIESCocaine affects multiple neurotransmitters, including release and reuptakeblockade of dopamine, norepinephrine, and serotonin (Koe, 1976). Many medications,including antidepressants, anticonvulsants, and dopaminergic agents,have been studied as potential treatments for cocaine dependence. However,none has been proven an effective pharmacotherapy in randomized, controlledclinical trials, and none have been approved by the U.S. Food and DrugAdministration (FDA) for this indication (Boyarsky & McCance-Katz, 2000;Jin & McCance-Katz, 2003; McCance-Katz, 1997; Silva de Lima et al., 2002).One outpatient, randomized clinical trial in which disulfiram, 250 mgdaily, was administered in combination with psychotherapies in cocainedependent,alcohol-abusing patients showed that disulfiram significantly reducedcocaine and alcohol use. Few adverse events were observed in this study(Carroll, Nich, Ball, McCance, & Rounsaville, 1998). A 1-year follow-up evaluationwith 96 of the participants in this study showed that the effects ofdisulfiram in reducing cocaine and alcohol use were sustained (Carroll et al.,2000). Subsequently, Petrakis and colleagues (2000) showed, in a double-blind,randomized, controlled study, that disulfiram treatment decreased cocaine andalcohol use in methadone-maintained patients who were also cocaine dependent.George and colleagues (2000) showed similar findings in buprenorphinemaintained,opioid-addicted patients who were also cocaine dependent.Naltrexone, an opioid antagonist approved for the treatment of opioid andalcohol dependence, is also being examined as a treatment for cocaine dependence.Although results of earlier studies in patients with comorbid cocaine andalcohol dependence were not encouraging, Oslin and colleagues (1999) reportedthat dosing of naltrexone, 150 mg daily, in cocaine- and alcoholdependentindividuals was associated with decreased cocaine and alcohol use.Naltrexone, 50 mg daily, was found to be associated with significantly lesscocaine use when administered in combination with relapse prevention therapy(Schmitz, Stotts, Rhoades, & Grabowski, 2001). The results from these studiessuggest that the effectiveness of naltrexone may depend on multiple factors,including other substance comorbidity, dose of naltrexone, length of treatment,