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This article aims to provide an overview of standard and adjunctive treatment options in opioid dependence in consideration of therapy-refractory courses. The relevance of oral opioid substitution treatment (OST) and measures of harm reduction as well as heroin-assisted therapies are discussed alongside non-pharmacological approaches. Currently, recommendation can be given for OST with methadone, buprenorphine, slow-release oral morphine (SROM), and levomethadone. Heroin-assisted treatment using diamorphine shall be considered as a cost-