Table 1.

Summary of literature on clinical management of withdrawal symptoms from methamphetamine and other amphetamine-type stimulants

Author	Year	Journal	Design	N	Treatments	Timeframe	Withdrawal-related findings
Birath, B. et al. a	2017	Drug and Alcohol Dependence	Randomized placebo-controlled pilot trial	11	Ibudilast (0 mg, 50 mg, 100 mg each for 5 days)	27 days hospitalized with last assessment at day 22	Significantly reduced variability in response time to an attention task compared to placebo.
Black, D.S. & Amaro, H. a,†	2019	Behavioral Research and Therapy	Randomized-controlled trial; residential treatment setting	200	Mindfulness-based intervention (80 min sessions, 2 per week); psychoeducation control	6 weeks; abstinence began upon admission to setting	Greater retention that the control group.
Brooks, S. et al. a	2016	NeuroImage: Clinical	Non-randomized controlled trial	66	Working memory training (30 mins per day) plus TAU; TAU	8 weeks; no definition of start of abstinence at baseline	Increases of the bilateral basal ganglia and reduced bilateral cerebellum volume; improvements in self-reported impulsivity scores in the working memory training group, but not in the treatment-as-usual group.
Cruickshank, C.C. et al. a	2008	Drug and Alcohol Review	Randomized placebo-controlled pilot trial	31	Mirtazapine (30 mg nocte); placebo	Treatment during first 2 weeks of withdrawal period with follow-up at day 35	No significant association with retention in out-patient withdrawal treatment
Glasner-Edwards, S. et al. a,†	2017	Mindfulness	Randomized-controlled trial	63	Mindfulness-based relapse prevention (8 weekly groups); health education (8 weekly groups)	12-week trial; 4 weeks contingency management lead in then randomized to: 8 weeks MBRP+CM; 8 weeks HE+CM	Mindfulness-based intervention plus contingency management showed significantly greater reductions in depression and anxiety symptoms compared to Health Education for those with MDD or GAD.
Hester, R. et al. a	2010	Experimental and Clinical Psychopharmacology	Randomized placebo-controlled pilot trial	20	Modafinil (200 mg/d); placebo	First 7 days of withdrawal	Significantly improved verbal recall and nonsignificant—but improved—executive function and delayed memory tasks compared to placebo.
Heinzerling, K.G. et al. b	2010	Drug and Alcohol Dependence	Randomized placebo-controlled trial	71	Modafinil (400 mg/d); placebo	12 weeks following randomization	No significant association with depressive symptoms, cravings, and retention
Jayaram-Lindström et al. b,‡	2008	American Journal of Psychiatry	Randomized placebo-controlled trial	80	Naltrexone (50 mg/d); placebo	12 weeks outpatient; 2 weeks abstinence prior to starting medication	Significantly greater reduction in craving
Kongsakin, R. et al. a,‡	2005	International Clinical Psychopharmacology	Randomized placebo-controlled trial	20	Mirtazapine (15 mg/d titrated to 60 mg/d depending on response)	14 days, during detoxification	Significantly greater improvement in Amphetamine Withdrawal Questionnaire scores, anxiety, and hyperarousal compared to placebo at days 3 and 14
Liang, Y. et al. a	2018	JAMA Psychiatry (research letter)	Randomized placebo-controlled trial	50	Repetitive transcranial magnetic stimulation (10 Hz, left DLPFC); sham	Two sessions daily for five days with two days between sessions following initial abstinence of 1–15 days	Significantly greater reductions in withdrawal symptoms, craving, depressive symptoms, anxiety symptoms, and greater improvements in sleep quality compared to placebo.
McGregor, C. et al. a	2008	Journal of Substance Abuse Treatment	Three-group clinical trial comparing modafinil, mirtazapine, and historical treatment-as-usual	49	Modafinil (400 mg/d); mirtazapine (60 mg/d); periciazine (2.5–5 mg/d)	First 10 days of withdrawal	Significantly lower Amphetamine Cessation Symptom Assessment scores in modafinil and mirtazapine groups compared to periciazine group; greater hours of sleep but more sleep disturbance in the mirtazapine group compared to the modafinil group.
Miles, S.W. et al. b,‡	2013	Addiction	Randomized-controlled trial	79	Extended release methylphenidate (54 mg/d); placebo	22 weeks following randomization	No significant difference in craving compared to placebo, though retention was higher in those who received methylphenidate.
Rawson, R.A. et al. a	2015	Journal of Substance Abuse Treatment	Randomized controlled trial	135	Exercise (45 mins high intensity, 3 per week) plus TAU vs Health education (3 per week) plus TAU	8 weeks, recruited upon entry in residential treatment	Significantly greater reductions in depressive and anxiety symptoms compared to health education control group.
Srisurapanont, M. et al. a,‡	1999	Australian and New Zealand Journal of Psychiatry	Randomized-controlled trial	44	Amineptine (100 mg/d); placebo	2-week inpatient trial; abstinence started < 5 days prior to randomization	Amineptine reversed decreased energy, increased appetite and craving for sleep compared to placebo
Su, H. et al. a	2017	Drug and Alcohol Dependence	Randomized placebo-controlled pilot trial	30	Repetitive transcranial magnetic stimulation (10 Hz, left DPLFC); sham	3 weeks, but duration of initial abstinence not reported	Significantly greater improvements in verbal learning, memory, and social cognition compared to sham.
Thompson, R.G., Jr. et al. b	2021	Journal of Psychopharmacology	Randomized placebo-controlled pilot trial with planned crossover	34	d-amphetamine (60 mg/d); placebo	4 weeks following randomization	Significant attenuation of craving compared to placebo group; heart rate elevated in placebo during week 1
Trivedi, M. et al. b	2021	New England Journal of Medicine	Randomized placebo-controlled trial	403	Bupropion (450 mg/d) with extended release naltrexone (380mg at 3 weeks); placebo	12-week trial; assessments collected weeks 5–6 and 11–12.	Lower craving for combination treatment compared to placebo in assessment weeks

^aSymptom-focused trial during the withdrawal period.

^bStimulant use reduction trial reporting withdrawal symptoms.

^†Study participants included both people who used methamphetamine and people who used cocaine.

^‡Study participants included those who used any amphetamine-type stimulant.