Pharmacological management of psychoactive substance withdrawal syndrome

Rationale Medications are available to manage alcohol and drug withdrawal, but they are underutilized. Only a handful, such as methadone, buprenorphine, clonidine, or benzodiazepines (chlordiazepoxide, lorazepam, or diazepam), are prescribed. Objectives Our objective was to provide an adjusted, inclusive, critical review of the clinical benefits of medications studied for the management of psychoactive substance withdrawal syndrome. Methods We performed an electronic literature search for randomized controlled trials (RCTs) and systematic reviews of RCTs with or without meta-analysis by free-text searching for pharmacotherapy on drug and alcohol withdrawal in eight databases. Results Doxepin, citalopram, doxepin, and pregabalin manage dysphoria and anxiety during opioid withdrawal. Gabapentin and atenolol lessen alcohol cravings. Gabapentin improves the sleep difficulties associated with cannabis withdrawal. Melatonin reduces anxiety, irritability, depressed mood, and cravings for nicotine. Doxepin alleviates benzodiazepine withdrawal anxiety and depression. Riluzole reduces amphetamine craving and depression. Modafinil reduces the intensity of cocaine cravings. Controlled trials on caffeine withdrawal were lacking. Buspirone and gabapentin accounted for more than 70% of all the medications studied. No conclusions can be drawn on adverse events because of reporting inconsistencies in the studies reviewed. Conclusions Substitution therapy seems to be the foremost choice for the treatment of psychoactive substance withdrawal. However, other medications are available but poorly utilized. Practitioners can use the armory of other available medications to manage psychoactive substance withdrawal. Patients can broaden their medication choice. Voltage-gated ion channels are a promising niche to explore.