Pharmacotherapy of Dual Substance Abuse and Dependence

Department of Community Health, Center for Alcohol and Addiction Studies, Brown University, Providence, Rhode Island, USA.
CNS Drugs (Impact Factor: 5.11). 12/2006; 21(3):213-237. DOI: 10.2165/00023210-200721030-00003


The US FDA has approved a limited number of treatments for alcohol, nicotine and opioid dependence; however, no treatments for other abused drugs such as marijuana, cocaine or methamphetamine are approved. This review focuses on research into drug pharmacotherapies, particularly single-drug therapies, for substance abuse and dependence contributing to the most important dual substance use disorders (SUDs). Given the implications of poly-substance abuse, it is essential that clinicians and researchers be aware of potential pharmacotherapies for the treatment of dual SUDs.
A substantial number of patients abuse more than one drug concurrently, complicating the treatment of SUD and leaving clinicians with few FDA-approved drug options for their patients. In this era of evidence-based medicine, such patients are typically treated with therapeutically proven medications, but in ways that are outside the scope of a drug’s original indication by the FDA. Such ‘off-label’ prescribing has become an important therapeutic strategy for practitioners seeking treatments for other diseases in subpopulations such as paediatrics and gerontology or for medical conditions such as oncology or mental illness. Similarly, the information that most clinicians use to make their decisions for treating patients abusing multiple drugs stems from trials treating a single SUD, anecdotal experiences from their own practice or that of their colleagues, or single-case studies reported in the literature.
The existing evidence suggests there are few treatments for SUDs that confer significant reductions in substance use across a broad patient population. Moreover, even fewer clinical efficacy trials have been conducted that provide evidence of therapeutic benefit for these drugs. Recognising the difficulty in making the proper drug choice for facilitating maximum treatment success, this review highlights the single drugs or drug combinations that show some potential for treating dual SUDs. This review finds strongest support for the use of disulfiram for treatment of alcohol and cocaine dependence (with or without concomitant methadone maintenance), baclofen for alcohol and cocaine dependence (but not opioid-dependent cocaine users), tiagabine for cocaine dependence in methadone-maintained patients, and topiramate for alcohol, nicotine and cocaine dependence. While ondansetron and olanzapine show some efficacy in treating alcohol and cocaine dependence, more research is needed to better delineate the subpopulation in which these drugs may provide their maximum effect.

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    • "It may also represent the conclusion of a prolonged opioid-replacement therapy (Kleber, 2007). Either way, given the economic implications and the high incidence and severity of dual and polysubstance abuse and dependence among opioid addicts, the importance of identifying specifi c pharmacotherapies has been repeatedly emphasized (Kenna et al., 2007; Kosten, 1991; Kreek, 1988; Stimmel et al., 1981). Thus, it is surprising that a medication approved for the treatment of both alcohol and opioid dependence, such as naltrexone, has received little attention. "
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    ABSTRACT: The influence of alcohol use on opioid dependence is a major problem that warrants a search for more effective treatment strategies. The addition of very-low-dose naltrexone (VLNTX) to methadone taper was recently associated with reduced withdrawal intensity during detoxification. In a secondary analysis of these data, we sought to determine whether problem drinking affects detoxification outcomes and whether symptoms are influenced by VLNTX use. Opioid-dependent patients (N = 174) received naltrexone (0.125 or 0.250 mg/day) or placebo in a double-blind, randomized design during methadone-based, 6-day inpatient detoxification. Alcohol consumption was assessed at admission using the Addiction Severity Index and selfreport. Outcome measures were opioid withdrawal intensity, craving, and retention in treatment. Problem drinking-opioid dependent patients (n = 79) showed episodic heavy alcohol use and reported increased subjective opioid withdrawal intensity (p = .001), craving (p = .001), and significantly lower rate of retention in treatment (p = .02). Individuals with problem drinking and opioid dependence who were treated with VLNTX (n = 55) showed reduced withdrawal (p = .05) and a lower rate of treatment discontinuation (p = .03), resuming alcohol intake in smaller numbers the day following discharge (p = .03). Treatment effects were more pronounced on anxiety, perspiration, shakiness, nausea, stomach cramps, and craving. There were no group differences in use of adjuvant medications and no treatment-related adverse events. Heavy drinking is associated with worse opioid detoxification outcomes. The addition of VLNTX is safe and is associated with reduced withdrawal symptoms and better completion rate in these patients. Further studies should explore the use of VLNTX in detoxification and long-term treatment of combined alcohol-opioid dependence and alcohol dependence alone.
    Full-text · Article · May 2011 · Journal of studies on alcohol and drugs
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    • "The problem of dependence and tolerance is the major limiting factor in medical opioid usage.1 If this problem can be dissociated or tackled somehow, opioid use can again become popular as they are the most effective drugs for the management of pain.2 Extensive research is going on for the development of non-addicting opioids and/or agents that can prevent or reverse the addiction processes. "
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    ABSTRACT: The present study was conducted to investigate the effect of potassium channel openers and blockers on morphine withdrawal syndrome. Mice were rendered dependent on morphine by subcutaneous injection of morphine; four hours later, withdrawal was induced by using an opioid antagonist, naloxone. Mice were observed for 30 minutes for the withdrawal signs ie, the characteristic jumping, hyperactivity, urination and diarrhea. ATP-dependent potassium (K(+) (ATP)) channel modulators were injected intraperitoneally (i.p.) 30 minutes before the naloxone. It was found that a K(+) (ATP) channel opener, minoxidil (12.5-50 mg/kg i.p.), suppressed the morphine withdrawal significantly. On the other hand, the K(+) (ATP) channel blocker glibenclamide (12.5-50 mg/kg i.p.) caused a significant facilitation of the withdrawal. Glibenclamide was also found to abolish the minoxidil's inhibitory effect on morphine withdrawal. The study concludes that K(+) (ATP) channels play an important role in the genesis of morphine withdrawal and K(+) (ATP) channel openers could be useful in the management of opioid withdrawal. As morphine opens K(+) (ATP) channels in neurons, the channel openers possibly act by mimicking the effects of morphine on neuronal K(+) currents.
    Preview · Article · Nov 2010 · Substance Abuse: Research and Treatment
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    • "Research results also support the clinical and treatment implications of polydrug use, in terms of greater psychopathology (Beswick et al., 2001; Booth et al 2006; Malcolm et al., 2006; also Medina and Shear, 2007; Sumnall et al., 2004); higher levels of health risk behaviors (Patterson et al., 2005); and difficulties in engaging in treatment (John et al., 2001). There are also challenges in developing effective treatment approaches for polydrug users because of the different psychological and physiological effects of different substances (Kenna et al., 2007). While evidence is not consistent (Prendergast et al., 2002), several studies focusing primarily on heroin and cocaine use found polydrug use to be negatively related to treatment outcomes (Bovasso and Cacciola, 2003; DeMaria, et al., 2000; Downey et al., 2000; Williamson et al., 2006). "
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    ABSTRACT: A typical approach to categorizing substance users for epidemiologic purposes or to identify substance use problems at treatment admission is by indicating the primary substance used and/or for which treatment is sought. But does such singular focus on the primary drug limit the validity of conclusions from longitudinal analysis of drug use patterns over time? This analysis combined data from five longitudinal studies conducted in California and examined 10-year patterns of heroin, cocaine, methamphetamine (meth), marijuana, and alcohol use for primary users of heroin (n=629), cocaine (n=694), and meth (n=474). Results suggest relatively low levels of use of non-primary heroin, cocaine, and meth, but moderate levels of alcohol and marijuana use. Growth models showed declining primary drug levels for heroin and meth users and relatively consistent levels over 10 years for cocaine users, while levels of non-primary drugs remained at consistently low levels or declined in tandem with the primary drug. Results indicate that group descriptions of primary heroin, cocaine, or meth use trajectories over time may present valid information about drug use patterns in general.
    Full-text · Article · Sep 2008 · Drug and Alcohol Dependence
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