Open-Label Pilot Trials of Mirtazapine and Modafinil in Inpatient Methamphetamine Withdrawal: Symptoms and Sleep Patterns

Catherine McGregor

McGregor, Catherine; White, Jason, M.; Srisurapanont, Manit; Mitchell, Amanda University of Adelaide/ University of Adelaide, Australia, Drug and Alcohol Services Council, Australia/ Chiang Mai University, Thailand/ Drug and Alcohol Services Council, Australia

Methamphetamine dependence has been linked to a range of harms including psychosis and high-risk HIV behaviors. Identification of an effective pharmacotherapy for withdrawal symptom suppression would be of considerable value. We investigated the efficacy of the noradrenergic and serotonergic antidepressant mirtazapine (15–60 mg per day, n=13), and the wake-promoting drug, modafinil (400mg per day, n=14) in successive, open-label pilot trials in inpatients undergoing withdrawal management. Study medication was administered for up to ten days and the effects on withdrawal symptoms measured by subjective (Amphetamine Cessation Symptom Assessment scale) and observer-rated (Clinical Global Impressions scale) measures and a sleep questionnaire. A historical comparison group (n=22) received treatment as usual (TAU), consisting of pericyazine 2.5–10mg per day for control of agitation. Symptomatic medications including non-opioid analgesics, anxiolytics and sedatives were administered on anas-needed basis to all subjects. Modafinil and mirtazapine were well-tolerated and produced minimal positive subjective effects. There were significant group differences in withdrawal severity (F=18.6, df 2,219 p<.0001). Post-hoc analysis showed that modafinil was more effective than mirtazapine (p=.012), and both were more effective than TAU (p<.001 and p=.025, respectively) in ameliorating withdrawal symptom severity. Modafinil group subjects had significantly lower observer-rated withdrawal severity compared to the mirtazapine (p=.014) and TAU (p<.001) groups. Modafinil group subjects had less hypersomnia (p=.012), had fewer night time awakenings (p=.010) and slept more deeply (p=.019) compared to those receiving mirtazapine. There were no differences in treatment retention between the three study groups. Both drugs showed promise as pharmacotherapies for amphetamine withdrawal, although modafinil was more effective overall, particularly in normalizing sleep patterns.

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