Elsevier

Drug and Alcohol Dependence

Volume 85, Issue 1, 15 October 2006, Pages 12-18
Drug and Alcohol Dependence

Randomized, placebo-controlled trial of sertraline and contingency management for the treatment of methamphetamine dependence

https://doi.org/10.1016/j.drugalcdep.2006.03.005Get rights and content

Abstract

Background

Methamphetamine dependence and associated medical and psychiatric concerns are significant public health issues. This project evaluated the efficacy of sertraline (50 mg bid) and contingency management (CM) for the treatment of methamphetamine dependence.

Method

In this randomized, placebo-controlled, double-blind trial, participants completed a 2-week non-medication baseline and were randomized to one of four conditions for 12 weeks: sertraline plus CM (n = 61), sertraline-only (n = 59), matching placebo plus CM (n = 54), or matching placebo-only (n = 55). All participants attended clinic thrice-weekly for data collection, medication dispensing, and relapse prevention groups. Outcomes included methamphetamine use (urine drug screening and self-reported days of use), retention (length of stay), drug craving (visual analogue scale), and mood symptoms (Beck Depression Inventory).

Results

No statistically significant main or interaction effects for sertraline or CM in reducing methamphetamine use were observed using a generalized estimating equation (GEE), although post hoc analyses showed the sertraline-only condition had significantly poorer retention than other conditions (χ2 (3) = 8.40, p < 0.05). Sertraline conditions produced significantly more adverse events than placebo conditions. A significantly higher proportion of participants in CM conditions achieved three consecutive weeks of methamphetamine abstinence than those in non-CM conditions.

Conclusions

These data do not demonstrate improved outcomes for sertraline versus placebo for treatment of methamphetamine dependence; indeed, they suggest sertraline is contraindicated for methamphetamine dependence. Findings provide support for the use of contingency management for treatment of methamphetamine dependence.

Introduction

The proliferation of methamphetamine dependence, and its serious consequences to medical, public health, law enforcement, and criminal justice systems in broad sections of the United States, has engendered an urgent need for effective interventions. Treatment admissions for methamphetamine dependence now outpace those for cocaine or heroin dependence in broad sections of the country (CESAR, 2005). In addition to the numerous criminal justice (Hser et al., 2004, Cretzmeyer et al., 2003), medical, and psychiatric sequela (Peck et al., 2005a) of methamphetamine dependence, it is strongly associated with HIV and other infectious diseases among men who have sex with men (Shoptaw et al., 2005, Patterson et al., 2005), and increasingly among populations historically considered at lower risk for HIV (CDC, 2004).

Methamphetamine withdrawal symptoms, including fatigue, anhedonia, depressed mood, and hypersomnia, are common to depression and are often severe enough to precipitate relapse (Peck et al., 2005b). Methamphetamine produces neurotoxic effects in monoaminergic neurons and related neural structures also associated with depression (Guilarte et al., 2003). Early work demonstrating that lesions or neurotoxins that inhibit 5-HT signaling caused animals to consistently self-administer more amphetamine (Leccese and Lyness, 1984, Lyness et al., 1980) suggested potential usefulness of 5-HT reuptake inhibitors in decreasing the reinforcing effects of methamphetamine and associated neurotoxicity. This strategy has been implemented in trials of the selective serotonin reuptake inhibitors (SSRIs) fluoxetine (Batki et al., 1999) and paroxetine (Piasecki et al., 2003), both of which have shown no efficacy for reducing methamphetamine use.

Although efforts to develop an effective pharmacotherapy for methamphetamine dependence have been unsuccessful, behavioral and cognitive behavioral therapies have shown efficacy for reducing stimulant use (Carroll et al., 2004, Rawson et al., 2004) and the depressive symptoms associated with methamphetamine use (Peck et al., 2005b). Contingency management (CM) is an application of operant conditioning that manipulates available reinforcers to shape behavior. There is substantial evidence to support its use for treatment of dependence on alcohol and numerous drugs including heroin, cocaine, and marijuana, for improving treatment-related outcomes (see Carroll and Onken, 2005 for review), and more recently with methamphetamine-dependent individuals (Shoptaw et al., 2005). The Matrix Model is an integrative psychosocial intervention that blends elements of motivational interviewing, family education, relapse prevention, and psychoeducational skills training. Matrix Model treatment outperformed standard treatments in a multi-site clinical trial of interventions for methamphetamine dependence (Rawson et al., 2004) and the model has been used as a psychosocial platform in clinical trials of medications for stimulant dependence (Shoptaw et al., 2003).

This study conducted a randomized placebo-controlled trial of sertraline, a potent SSRI with a strong safety profile, and of contingency management for methamphetamine dependence using a counseling platform of Matrix Model relapse prevention groups. The primary outcomes were defined a priori as methamphetamine use and retention in treatment. Secondary outcomes included craving for methamphetamine, depression, and adherence to study medication. It was predicted that participants assigned to receive sertraline would achieve significantly greater reductions in methamphetamine use and significantly longer retention in treatment than participants assigned to receive placebo, and that this effect would be optimized using contingency management. It was also predicted that participants assigned to receive sertraline would report significantly greater reductions in methamphetamine cravings and depressive symptoms, and would achieve significantly better adherence to study medication regimen than those assigned to receive placebo.

Section snippets

Participants

The Friends Research Institute West Coast Institutional Review Board provided oversight of all procedures in accordance with the Belmont Report.

Participants were males and females (non-pregnant and non-lactating) between the ages of 18 and 65 who met criteria for methamphetamine abuse or dependence verified by the Structured Clinical Interview for the DSM-IV (SCID; Spitzer et al., 1995). Potential participants were excluded if they had a primary medical condition that might interfere with safe

Sample characteristics

A total of 414 treatment-seeking individuals with methamphetamine abuse or dependence began screening procedures for this study (Fig. 1). Of these, 229 participants were randomized to study condition: sertraline plus CM (n = 61), sertraline-only (n = 59), placebo plus CM (n = 54), or placebo-only (n = 55). Participants not randomized to the trial reported heavier use of methamphetamine than those randomized to the study as measured by number of days of methamphetamine use in the 30 days prior to study

Discussion

Study results did not confirm project hypotheses. There were no statistically significant main or interaction effects for the medication or behavioral therapies delivered in this trial along measures of methamphetamine use, retention, drug craving, depression, or medication adherence. Moreover, sertraline appeared to worsen methamphetamine use, as indicated by the greater number of urine samples positive for methamphetamine metabolites and reduced likelihood of achieving three consecutive weeks

Acknowledgements

The authors gratefully acknowledge support from the National Institute on Drug Abuse for the conduct of this study and the analysis of these data from grants 1 R01 DA 010923 and 1 P50 DA 018185. Medication and placebo were provided by Pfizer Inc.

References (29)

  • Centers for Disease Control and Prevention (CDC), 2004. HIV/AIDS Surveillance Report, 2003, vol. 16. US Department of...
  • Center for Substance Abuse Research (CESAR), 2005. The Developing Methamphetamine Problem: Selected CESAR Publications...
  • Y.I. Hser et al.

    Relationship between drug treatment services, retention, and outcomes

    Psychiatr. Serv.

    (2004)
  • W. Ling et al.

    Treatment effectiveness score as an outcome measure in clinical trials. Medication development for the treatment of cocaine dependence: issues in clinical efficacy trials

    NIDA Research Monograph

    (1997)
  • Cited by (119)

    • Types of addiction

      2023, Substance Use and Addiction Research: Methodology, Mechanisms, and Therapeutics
    • Contingency management for the treatment of methamphetamine use disorder: A systematic review

      2020, Drug and Alcohol Dependence
      Citation Excerpt :

      Roll and Shoptaw (2006) found that methamphetamine dependent participants assigned to an escalating-with-reset contingency management schedule condition submitted more methamphetamine negative samples and achieved longer periods of abstinence than participants in the escalating-without-reset condition. Shoptaw et al. (2006a) reported that significantly more participants who met criteria for methamphetamine abuse or dependence assigned to either a contingency management + sertraline or contingency management + placebo condition achieved three weeks of abstinence than participants assigned to either sertraline- or placebo-only conditions. Interestingly, participants in the contingency management groups achieved these results despite earning a considerably smaller proportion of the incentives than had been observed in earlier contingency management studies.

    • Effects of environmental enrichment on reinstatement of methamphetamine-induced conditioned place preference

      2020, Behavioural Brain Research
      Citation Excerpt :

      Reinstatement to drug use is considered among the main problems in the treatment of substance use disorder; therefore, its prevention is an essential goal. Unfortunately, different pharmacological agents have not shown promising results in clinical trials on METH dependence, and there is currently no approved pharmacotherapy for METH dependence [66–69]. Here, we have presented a non-pharmacological approach to the management of reinstatement to METH CPP in a rat model of drug addiction.

    View all citing articles on Scopus
    View full text