Treatment for amphetamine withdrawal.
BACKGROUND
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.


OBJECTIVE
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.


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


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


METHODS
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.


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.


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.
Department of Family Medicine, University of California, 10880 Wilshire Boulevard, Suite 540, Los Angeles, CA 90024, USA. sshoptaw@mednet.ucla.edu
Steven J
SJ
Shoptaw
Uyen
U
Kao
Keith
K
Heinzerling
Walter
W
Ling
D000661:Amphetamine / Q000009:adverse effects*; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use; D003913:Dextroamphetamine / Q000009:adverse effects; D003986:Dibenzocycloheptenes / Q000627:therapeutic use; D018765:Dopamine Uptake Inhibitors / Q000009:adverse effects*; D006801:Humans; D008694:Methamphetamine / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*
D000929:Antidepressive Agents, Tricyclic; D003986:Dibenzocycloheptenes; D018765:Dopamine Uptake Inhibitors; C011597:amineptin; D008694:Methamphetamine; D000661:Amphetamine; D003913:Dextroamphetamine