Amphetamine withdrawal : nature, time course and treatment.

Abstract

Increased demands on amphetamine dependence treatment services point to a need for effective pharmacotherapies for withdrawal symptom suppression. However, empirical data on which to base effective treatments are scarce. To address the need for an evidence base, four studies were conducted in two countries - Australia and Thailand. Firstly, the time course and severity of amphetamine withdrawal symptoms were characterised in two inpatient samples of amphetamine users. Results identified the first week of abstinence as an acute withdrawal phase characterised by increased sleeping, eating and a cluster of mood and anxiety - related symptoms. Following the acute phase, most withdrawal symptoms remained stable and at low levels for the remaining two weeks of abstinence ( the sub - acute phase ). Data from these two studies formed the basis for a new instrument, the Amphetamine Cessation Symptom Assessment scale ( ACSA ). On psychometric testing, the ACSA showed satisfactory reliability and a clear psychometric structure, delineating symptom clusters and their correlates with a three factor solution providing the best fit to the data. Using the ACSA to measure outcome, the safety and efficacy of the serotonin and noradrenaline reuptake inhibitor antidepressant mirtazapine ( 15 - 60 mg per day, n = 13 ), and the wake-promoting drug, modafinil ( 400mg per day, n = 14 ) were assessed in successive, open - label, inpatient pilot trials. Study medication was administered for up to ten days. An historical comparison group ( n = 22 ) who received treatment as usual consisting of pericyazine 2.5 - 10mg per day for control of agitation served as a comparison. Results showed that modafinil and mirtazapine were well tolerated, producing minimal positive subjective effects. There were significant group differences in withdrawal severity ( F = 18.6, df 2,219 p < 0.001 ). Post - hoc analysis showed that modafinil was more effective than mirtazapine ( p = 0.041 ), and both were more effective than treatment as usual ( both p < 0.001 ) in ameliorating withdrawal severity. Overall, these studies identified a peak in withdrawal severity during the first week of abstinence ; demonstrated the reliability and validity of the ACSA and identified modafinil as a safe and potentially effective pharmacotherapy for the treatment of amphetamine withdrawal symptoms.