Table 1.

Dopamine agonists and antagonists

Pharmacological agents	Study design Sample characteristics	Outcomes	Results	Main limitations	References
Modafinil (400 mg day−1)	10-day open-label study 14 methamphetamine dependent patients seeking treatment Amphetamine use for at least 3 days a week over the previous month Amphetamine use within the previous 96 h	Primary outcomesWithdrawal syndrome Sleep disturbance Secondary outcomesTolerance Adverse effects or events	Milder withdrawal syndrome Less sleep disturbance Safe and well tolerated	Patients and clinicians aware of study group allocation Small sample size Study outcomes were assessed against a historical comparison group enrolled in a separate study	[53]
Modafinil (50 to 200 mg day−1) and HIV medications Modafinil (100 to 400 mg day−1) (not on HIV medications)	16-week pilot study: 12-week single blind trial + 4-week placebo phase 13 patients seeking to reduce or stop methamphetamine use Seven of 13 met DSM-IV criteria for stimulant abuse and 6 for dependence Mean duration for abuse or dependence: 43 months Mean reported days of use/week: 4 Primary route of use: smoking (9 patients) HIV+ (11/13 men)	Primary outcomesSelf-reported use of days per week (urine toxicology assays) Secondary outcomesCraving (Methamphetamine Craving Scale; Obsessive/Compulsive Methamphetamine Use Scale) Depression (Beck Depression Inventory II) Side effects or adverse events	Decrease of methamphetamine use by >50% Decreased craving No side effects except in 2 patients	Difficulty in recruitment Low number of responders High attrition rates	[51]
Modafinil (200 mg day−1)	10-week randomized, double-blind, placebo-controlled clinical trial + 12-week post-treatment follow-up 80 methamphetamine-dependent subjects seeking treatment 2–3 days of methamphetamine use per week or more Most subjects injected methamphetamine on a daily basis, with a third who preferred to smoke it	Primary outcomeSelf-reported use of days per week (urine toxicology assays) Secondary outcomesTreatment retention Medication adherence Craving Severity of dependence Other substance dependence Adverse events	No differences in treatment retention, medication adherence, methamphetamine abstinence, craving or severity of dependence. More methamphetamine-negative urine samples in the modafinil group Significant reductions in systolic blood pressure and weight gain No medication-related serious adverse events	Absence of an objective quantitative measure, reliance on self-reported outcomes A sample size too small to detect reliably the small differences between modafinil and placebo	[54]
SR bupropion (300 mg day−1)	12-week double-blind placebo-controlled study and a 30-day follow-up 151 methamphetamine dependent patients seeking treatment Primary route of administration: smoking Days of methamphetamine use in last 30 days (less or equal to 18 days or superior to 18 days)	Primary outcomeChange in proportion of participants having a methamphetamine -free week. Secondary outcomesUrine for quantitative methamphetamine Self-report of methamphetamine use Subgroup analyses of balancing factors and comorbid conditions Addiction severity, craving Risk behaviours for HIV Use of other substances	Decrease of methamphetamine use (intent-to-treat analysis) Decreased use in male subjects who had low to moderate baseline use (less or equal to 18 days per month) (Subgroup analysis)	Poor therapeutic response in female patients Imbalance between groupson the presence of ADHD (15% of participants) Lack of training for inter-rater reliability between raters using DSM-IV checklist	[60]
SR bupropion (300 mg day−1)	12-week randomized, double-blind, placebo-controlled clinical trial 73 methamphetamine dependent patients	Primary outcomeMethamphetamine use (as assessed via urine drug screens) Secondary outcomesTreatment retention Severity of depressive symptoms Methamphetamine craving Adverse effects Cigarette smoking among methamphetamine dependent patients	Significant decrease of methamphetamine use among light users (post hoc analysis) Decrease of self-reported cigarette use	Small sample size Lowered power of the study Attrition of the participants	[61]
SR methylphenidate (54 mg day−1)	20-week randomized placebo controlled trial With 3 arms including aripirazole and placebo as well as methylphenidate 17 amphetamine or methamphetamine dependent patients 5 women, HIV infection (n= 4), hepatitis B or C infection (n= 13) Duration of use: 15 years	Primary outcomeProportion of amphetamine-positive urine samples Secondary outcomesAdverse effects	Decrease of amphetamine intravenous use in the SR methylphenidate group reaching significance after 18 weeks (intention-to-treat analysis) No adverse effects	Small sample size Long period of time to achieve full benefit from this treatment	[67]
d-amphetamine (from 20 to 60 mg day−1)	12-week open, two-group pre-post randomized controlled trial 41 amphetamine dependent patients seeking treatment d-amphetamine group (n= 20) and control group (counselling (n= 21))	Primary outcomeAmphetamine and methamphetamine use (urine toxicology assays). Secondary outcomesAdverse events Psychotic symptoms	Reduced amphetamine use and severity of dependence in both group d-amphetamine group significantly more likely to attend counselling and receiving twice as many sessions as the control group. No adverse events or psychotic symptoms	Small sample size Study group restricted to subjects who were able to attend an inner-city clinic on a daily basis Possible selective attrition bias	[70]
SR d-amphetamine (from 20 to 110 mg day−1)	16-week randomized double blind, placebo-controlled clinical trial 49 methamphetamine dependent patients Positive urine sample and use of methamphetamine on 3 or more days per week over the previous 12 months Sufficient hair length for hair analysis	Primary outcomesMethamphetamine use and degree of dependence over time, and treatment retention. Secondary outcomesAdverse effects	Better retention in treatment in the SR d-amphetamine group Lower degree of methamphetamine dependence Trend to a greater reduction in self-reported methamphetamine use No serious adverse events	High attrition rates in the placebo group Number of subjects in each group	[71]
Risperidone (3.6 mg day−1)	4-week open-label study 11 veteran methamphetamine dependent patients seeking treatment	Primary outcomeSelf-reports of substance use (urine drug tests) Secondary outcomesAdverse effects	Decrease of methamphetamine use	Small sample size No placebo group	[77]