Effects of lofexidine on stress-induced and cue-induced opioid craving and opioid abstinence rates: preliminary findings.
OBJECTIVE
A preliminary study examined whether lofexidine decreases stress-induced and cue-induced opioid craving and improves opioid abstinence in naltrexone-treated opioid-dependent individuals.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Sinha
Rajita
R
Department of Psychiatry, Yale University School of Medicine, 34 Park Street, Room S110, New Haven, CT 06519, USA. Rajita.sinha@yale.edu
Kimmerling
Anne
A
Doebrick
Cheryl
C
Kosten
Thomas R
TR
D000328:Adult; D016739:Behavior, Addictive / Q000188:drug therapy*; D003000:Clonidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003463:Cues; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D009271:Naltrexone / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D009293:Opioid-Related Disorders / Q000188:drug therapy* / Q000523:psychology; D055502:Secondary Prevention; D013315:Stress, Psychological; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000523:psychology; D013997:Time Factors; D016896:Treatment Outcome
D009292:Narcotic Antagonists; D009271:Naltrexone; D003000:Clonidine; C025655:lofexidine