Remarks y There is insufficient evidence to support use of naltrexone, dexamphetamine, methylphenidate, modafinil, topiramate, mirtazapine or bupropion for the treatment of stimulant use disorders in non-specialized settings. y The term “cocaine or stimulant use disorders” refers to diagnosis according to the ICD-10, DSM-IV criteria or equivalent ICD-11 and DSM-5 diagnosis. y Pharmacological treatment considered in the current review included: naltrexone, dexamphetamine, methylphenidate, modafinil, topiramate, mirtazapine and bupropion. y Most of the trials using above medicines had elevated dropout rates which severely impacted their results. y Mirtazapine is a promising alternative that was found to have a relevant impact on subgroups (cisgender men and transgender women who have sex with men). y The combination of depot naltrexone and bupropion had a small but statistically significant impact on methamphetamine use in a recent trial. y Any treatment or support for people using drugs or with drug use disorders should ensure ethical standards – including respect for human rights and the individual’s dignity, and never using humiliating or degrading interventions – in line with the WHO and UNODC International standards for the treatment of drug use disorders (147) (see Box 3.1).

Implementation considerations y Some medicines have potential for abuse and adverse effects (such as prescription amphetamines/ dexamphetamine and methylphenidate). y Service providers should assess psychosocial stressors (e.g. domestic abuse, unemployment) associated with methamphetamine or cocaine use and dependence and include appropriate psychosocial interventions in their treatment plan. y The costs of the medicines evaluated here can vary between countries. There is very little literature on cost-effectiveness and pharmacoeconomic aspects in general for medicines to treat methamphetamine dependence. y If implemented, any psychopharmacological treatment of stimulant dependence should carefully consider the specific clinical characteristics of each person receiving the treatment (e.g. higher risk of psychotic episodes with prescription psychostimulants among individuals with previous history of psychosis). The medicine choice should consider, besides effectiveness, factors such as demographic characteristics (e.g. higher risks and side-effects that may be associated with pregnancy or older age), side-effects profiles (e.g. cardiovascular effects, psychosis/mania, weight gain) and availability (e.g. continuous availability, costs). y Comorbidities and complications, namely cardiovascular events and psychosis, should be carefully monitored during the treatment of methamphetamine dependence.