Treatment for amphetamine withdrawal

Symptoms of amphetamine withdrawal during the initial days of abstinence from chronic amphetamine use can prompt individuals to return to regular drug use. No medications demonstrate significant effects over placebo in reducing symptoms of acute amphetamine withdrawal.

Amphetamines can make people feel more alert, and are prescribed for problems like depression and attention deficit order. Amphetamines can produce euphoria, and so are manufactured for recreational use. Ongoing use can lead to dependence, which can be as hard to recover from as dependence on heroin or cocaine.  The only randomized trials of amphetamine withdrawal agents have been of antidepressant drugs (amineptine and mirtazapine).   Amineptine was found to have limited benefits, showing improvement only on some subjective effects but is no longer on the market because of concerns over its abuse liability. The benefits of mirtazapine have been less clear based on two randomised controlled trials, with one showing improvements in amphetamine withdrawal symptoms and the other showing no differences in withdrawal outcomes when compared to placebo.  More research is needed.

Authors' conclusions: 

No medication is effective for treatment of amphetamine withdrawal. Amineptine showed reduction in discontinuation rates and improvement in clinical presentation compared to placebo, but had no effect on reducing withdrawal symptoms or craving. In spite of these limited benefits, amineptine is not available for use due to concerns over abuse liability when using the drug. The benefits of mirtazapine as a withdrawal agent are less clear based on findings from two randomised controlled trials: one report showed improvements in amphetamine withdrawal symptoms over placebo; a second report showed no differences in withdrawal symptoms compared to placebo.  Further potential treatment studies should examine medications that increase central nervous system activity involving dopamine, norepinephrine and/or serotonin neurotransmitters, including mirtazapine.

Read the full abstract...

Few studies examined treatments for amphetamine withdrawal, although it is a common problem among amphetamine users. Its symptoms, in particular intense craving, may be a critical factor leading to relapse to amphetamine use. In clinical practice, medications for cocaine withdrawal are commonly used to manage amphetamine withdrawal although the pharmacodynamic and pharmacokinetic properties of these two illicit substances are different.


To assess the effectiveness of pharmacological alone or in combination with psychosocial treatment for amphetamine withdrawals on discontinuation rates, global state, withdrawal symptoms, craving, and other outcomes.

Search strategy: 

MEDLINE (1966 - 2008), CINAHL (1982 - 2008), PsycINFO (1806 - 2008), CENTRAL (Cochrane Library 2008 issue 2), references of obtained articles.

Selection criteria: 

All randomised controlled and clinical trials evaluating pharmacological and or psychosocial treatments (alone or combined) for people with amphetamine withdrawal symptoms.

Data collection and analysis: 

Two authors evaluated and extracted data independently. The data were extracted from intention-to-treat analyses. The Relative Risk (RR) with the 95% confidence interval (95% CI) was used to assess dichotomous outcomes. The Weighted Mean Difference (WMD) with 95% CI was used to assess continuous outcomes.

Main results: 

Four randomised controlled trials (involving 125 participants) met the inclusion criteria for the review. Two studies found that amineptine significantly reduced discontinuation rates and improved overall clinical presentation, but did not reduce withdrawal symptoms or craving compared to placebo. The benefits of mirtazapine over placebo for reducing amphetamine withdrawal symptoms were not as clear.  One study suggested that mirtazapine may reduce hyperarousal and anxiety symptoms associated with amphetamine withdrawal. A more recent study failed to find any benefit of mirtazapine over placebo on retention or on amphetamine withdrawal symptoms.