Amineptine in the treatment of amphetamine withdrawal: a placebo-controlled, randomised, double-blind study. A placebo-controlled trial of mirtazapine for the management of methamphetamine withdrawal. Mirtazapine in amphetamine detoxification: a placebo-controlled pilot study.
Temporary inability to function without amphetamine and the experience of withdrawal syndrome enhance the tendency for repetitive use. The investigators proposed to examine the therapeutic effects of amineptine, an antidepressant with dopamine reuptake inhibition effect, for the treatment of amphetamine withdrawal. The 14-day study was carried out on a randomised, double-blind, placebo-controlled design. The authors assessed the severity of amphetamine withdrawal syndrome by using two measures and performed both end-point and intent-to-treat analyses. The results showed that amineptine helped relieve a depressed mood within one week and improved the general condition within 2 weeks. In conclusion, amineptine is effective in rapid relief of depressed mood and improves the general condition of patients with amphetamine withdrawal. Since the amphetamine withdrawal may last for several weeks, studies with longer duration should be conducted before incorporating amineptine into the clinical practice a of amphetamine withdrawal treatment. As an antidepressant with sedative and anxiolytic properties, mirtazapine may be an appropriate pharmacotherapy for methamphetamine withdrawal. This study sought to examine whether mirtazapine improves retention and alleviates methamphetamine withdrawal symptoms in an out-patient setting.
                An out-patient double-blind, randomised placebo-controlled trial of mirtazapine for the treatment of methamphetamine withdrawal was conducted (15 mg nocte for 2 days, 30 mg nocte for 12 days). Both groups were offered narrative therapy counselling. Measures recorded on days 0, 3, 7, 14 and 35 included: treatment retention, Amphetamine Cessation Symptoms Assessment, the Athens Insomnia Scale, the Brief Symptom Inventory, the Depression-Anxiety-Stress Scale (DASS), Severity of Dependence scale and the Opiate Treatment Index Drug Use subscale.
                Thirty-one participants were recruited (18 placebo, 13 mirtazapine) and 52% completed the 2-week medication phase. No significant differences between the mirtazapine and placebo groups in retention, or any symptom measure were observed, except greater DASS-anxiety and longer sleep duration were measured at baseline among the mirtazapine group.
                Results suggest that mirtazapine does not facilitate retention or recruitment in out-patient methamphetamine withdrawal treatment, although recruitment may have been insufficient to identify a significant treatment effect. The potential role of narrative therapy for methamphetamine dependent patients deserves further exploration. The present study aimed to assess the safety and efficacy of mirtazapine in amphetamine detoxification in a 14-day randomized, placebo-controlled pilot trial in a Thai population. Subjects retained at a Specialized Probation Center, Department of Probation, Ministry of Justice, Thailand (n=20), who met DSM-IV criteria for amphetamine dependence and the inclusion criteria of the study, were randomized for either mirtazapine treatment or placebo. Efficacy was assessed by the Amphetamine Withdrawal Questionnaire (AWQ) for amphetamine withdrawal symptoms and the Montgomery-Asberg Depression rating scale (MADRS) for depression. Mirtazapine safety was assessed by interview during each follow-up period on days 3 and 14 after treatment. Nine subjects were randomized to the mirtazapine group and 11 to the placebo group. Among the initial 20 subjects, 16 (seven in the mirtazapine and nine in the placebo group) completed the study. There were significant improvements in the total AWQ score changes in the mirtazapine group versus placebo both at days 3 (P<0.005) and 14 (P<0.030). Significant improvements in favour of mirtazapine were also seen in the hyperarousal and the anxiety subscale score changes at days 3 (P<0.029) and 14 (P<0.018), respectively. No significant differences were seen (P>0.05) in the MADRS scores changes within or between the groups. Mild adverse events, such as headache, sedation, nausea and vomiting, were reported. In conclusion, despite its small sample size, this randomized, placebo-controlled pilot trial lends support to the hypothesis that mirtazapine may be an option in the meager armamentarium of amphetamine detoxification treatment.
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.