Amphetamine dependence constitutes a public health problem with many consequences and complications. Amphetamine abuse refers to a maladaptive and hazardous pattern of use considered to be less severe than dependence. To date, no pharmacological treatment has been approved for amphetamine abuse or dependence, and psychotherapy remains the best treatment option.

Long-term amphetamine use reduces dopamine levels in the brain. Drugs increasing dopamine and mimicking the effects of amphetamines with lower abuse liability could be used as replacement therapy in amphetamine dependence. Several psychostimulants have been studied recently for this purpose.

In this review, the efficacy and safety of psychostimulants for amphetamine abuse or dependence were studied. We found eleven studies enrolling 791 amphetamine-dependent participants and assessing the effects of four different psychostimulants: dexamphetamine, bupropion, methylphenidate and modafinil. Psychosocial interventions were additionally provided to all participants. The studies were conducted in the USA, Australia or Northern Europe, and study length ranged from 8 to 20 weeks.

Psychostimulants did not reduce amphetamine use or amphetamine craving and also did not increase sustained abstinence in comparison with placebo. Retention in treatment was similar and low with both treatments. Psychostimulants also did not increase the risk of adverse events that were intense enough to induce dropouts.

Research with larger and longer trials is needed to determine whether psychostimulants can be a useful replacement therapy for patients with amphetamine abuse or dependence. The design of future trials should consider the level of dependence at study entry, the potency and the dose of the psychostimulant administered, the length of the trial and the representativeness of included participants.