CapítuloAbstract For the past decades, several antidepressants have been explored as possible therapeutic drugs to relieve SUD. Mirtazapine is an approved atypical medication for the treatment of moderate to severe MDD. However, several studies indicated that the dosage program, consisting of a dose of 30mg/kg of mirtazapine, administered for 30 days or more during the early phase of withdrawal does not cause sedation, leads to a decrease in the symptoms of depression and anxiety during prolonged periods of drug withdrawal, and generates a permanent reduction (even in the absence of mirtazapine) of the behavioral effects induced by simple or combined drug use in rodents and humans. These studies support the efficacy of mirtazapine in reducing the behavioral reinforcing effect induced by a wide variety of drugs. Mirtazapine meets the characteristics of a multitarget drug, which suggests that it can be used either in future clinical trials or as a key molecule design new drugs.