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Prog Neuropsychopharmacol Biol Psychiatry. 2016 Oct 3;70:148-61. doi: 10.1016/j.pnpbp.2015.11.003. Epub 2015 Nov 12.

Treatment-refractory substance use disorder: Focus on alcohol, opioids, and cocaine.

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Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Nussbaumstrasse 7, 80336 Munich, Germany; Privatklinik Meiringen, Postfach 612, CH-3860 Meiringen, Switzerland. Electronic address:
Center for Addictive Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Selnaustrasse 9, 8001 Zurich, Switzerland.


Substance use disorders are common, but only a small minority of patients receive adequate treatment. Although psychosocial therapies are effective, relapse is common. This review focusses on novel pharmacological and other treatments for patients with alcohol, opioid, or cocaine use disorders who do not respond to conventional treatments. Disulfiram, acamprosate, and the opioid antagonist naltrexone have been approved for the treatment of alcoholism. A novel, "as needed" approach is the use of the mu-opioid antagonist and partial kappa agonist nalmefene to reduce alcohol consumption. Other novel pharmacological approaches include the GABA-B receptor agonist baclofen, anticonvulsants such as topiramate and gabapentin, the partial nicotine receptor agonist varenicline, and other drugs. For opioid dependence, opioid agonist therapy with methadone or buprenorphine is the first-line treatment option. Other options include oral or depot naltrexone, morphine sulfate, depot or implant formulations, and heroin (diacetylmorphine) in treatment-refractory patients. To date, no pharmacological treatment has been approved for cocaine addiction; however, 3 potential pharmacological treatments are being studied, disulfiram, methylphenidate, and modafinil. Pharmacogenetic approaches may help to optimize treatment response in otherwise treatment-refractory patients and to identify which patients are more likely to respond to treatment, and neuromodulation techniques such as repeated transcranial magnetic stimulation and deep brain stimulation also may play a role in the treatment of substance use disorders. Although no magic bullet is in sight for treatment-refractory patients, some novel medications and brain stimulation techniques have the potential to enrich treatment options at least for some patients.


Alcoholism; Baclofen; Brain stimulation; Nalmefene; Opioid dependence

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