Effects of lofexidine on stress-induced and cue-induced opioid craving and opioid abstinence rates: preliminary findings.
ABSTRACT A preliminary study examined whether lofexidine decreases stress-induced and cue-induced opioid craving and improves opioid abstinence in naltrexone-treated opioid-dependent individuals.
Eighteen opioid-dependent patients were stabilized for 4 weeks with naltrexone (50 mg daily) and lofexidine (2.4 mg bid) before entering a 4-week randomized, double-blind placebo-controlled discontinuation study where one group continued on lofexidine for an additional 4 weeks, while the second was tapered to placebo (Lofexidine-naltrexone vs Placebo-naltrexone). Ten patients also participated in guided imagery exposure to stress, drug cue, and neutral scenarios in a single laboratory session.
Lofexidine-naltrexone patients had higher opioid abstinence rates and improved relapse outcomes as compared to the Placebo-naltrexone group. Furthermore, Lofexidine-naltrexone patients had significantly lower heart rates and an attenuated stress and drug cue-induced opioid craving response in the laboratory as compared to the Placebo-naltrexone group.
Although preliminary, these findings are the first to document lofexidine's potential in addressing stress-related opioid craving and relapse outcomes in humans. The results also suggest that combination therapies that target both drug-related reinforcement (naltrexone) and stress- and cue-related aspects of drug seeking could be beneficial in addiction relapse prevention. Further development of lofexidine to address stress-related opioid craving and relapse is warranted.
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ABSTRACT: Previous research has focused on developing theories of addiction that may explain behavior in cocaine- and methamphetamine-dependent individuals. The primary goal of this report was to compare and contrast the prevalence of self-reported measures of impulsivity, depression, lifetime stress and sensation-seeking in healthy controls versus individuals with cocaine or methamphetamine use disorders. Twenty-nine individuals with cocaine use disorders and 31 individuals with methamphetamine use disorders were matched with 31 healthy control participants on several demographic variables. All participants were administered behavioral questionnaires including the Barrett Impulsiveness Scale (assessing impulsivity), Beck Depression Inventory II (assessing depression), Life Stressor Checklist-Revised (assessing lifetime stress) and the Impulsive Sensation Seeking Scale (assessing sensation-seeking). When compared to healthy controls, individuals with cocaine and methamphetamine use disorders had significantly higher levels of impulsivity and sensation-seeking. In addition, when compared to healthy controls, individuals with cocaine use disorders had significantly higher Beck Depression Inventory II scores, while individuals with methamphetamine use disorders had significantly higher Life Stressor Checklist-Revised scores. The results revealed that there were significantly higher levels of impulsivity, depression and sensation-seeking in cocaine users and significantly higher impulsivity, lifetime stress and sensation-seeking in methamphetamine users when compared to healthy controls. © The Author(s) 2014.Journal of Psychopharmacology 11/2014; DOI:10.1177/0269881114560182 · 2.81 Impact Factor
Frontiers in Psychiatry 12/2014; 5:180. DOI:10.3389/fpsyt.2014.00180
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ABSTRACT: The authors tested whether clonidine blocks stress-induced seeking of heroin and cocaine. The study was also intended to confirm translational findings from a rat model of drug relapse by using ecological momentary assessment of patients' stress to test hypotheses about clonidine's behavioral mechanism of action. The authors conducted a randomized double-blind placebo-controlled clinical trial with 208 opioid-dependent patients at an outpatient buprenorphine clinic. The 118 participants (57%) who maintained abstinence during weeks 5-6 were continued on buprenorphine and randomly assigned to receive clonidine (N=61) or placebo (N=57) for 14 weeks. Urine was tested thrice weekly. Lapse was defined as any opioid-positive or missed urine test, and relapse as two or more consecutive lapses. Time to lapse and relapse were examined with Cox regressions; longest period of abstinence was examined with a t test, and ecological momentary assessment data were examined with generalized linear mixed models. In an intent-to-treat analysis, clonidine produced the longest duration (in consecutive days) of abstinence from opioids during the intervention phase (34.8 days [SD=3.7] compared with 25.5 days [SD=2.7]; Cohen's d=0.38). There was no group difference in time to relapse, but the clonidine group took longer to lapse (hazard ratio=0.67, 95% CI=0.45-1.00). Ecological momentary assessment showed that daily-life stress was partly decoupled from opioid craving in the clonidine group, supporting the authors' hypothesized mechanism for clonidine's benefits. Clonidine, a readily available medication, is useful in opioid dependence not just for reduction of withdrawal signs, but also as an adjunctive maintenance treatment that increases duration of abstinence. Even in the absence of physical withdrawal, it decouples stress from craving in everyday life.American Journal of Psychiatry 03/2015; DOI:10.1176/appi.ajp.2014.14081014 · 13.56 Impact Factor