Randomized, placebo-controlled trial of sertraline and contingency management for the 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.
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2020, Behavioural Brain ResearchCitation 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.