Sinha Rajita, Kimmerling Anne, Doebrick Cheryl, Kosten Thomas R
Department of Psychiatry, Yale University School of Medicine, 34 Park Street, Room S110, New Haven, CT 06519, USA.
Psychopharmacology (Berl). 2007 Mar;190(4):569-74. doi: 10.1007/s00213-006-0640-8. Epub 2006 Nov 29.
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.
一项初步研究探讨了洛非西定是否能降低应激诱导和线索诱导的阿片类药物渴求,并改善纳曲酮治疗的阿片类药物依赖个体的阿片类药物戒断情况。
18名阿片类药物依赖患者在进入为期4周的随机、双盲、安慰剂对照停药研究前,先用纳曲酮(每日50毫克)和洛非西定(每日两次,每次2.4毫克)稳定治疗4周。在该研究中,一组继续服用洛非西定4周,另一组逐渐减量至安慰剂(洛非西定-纳曲酮组与安慰剂-纳曲酮组)。10名患者还在一次实验室实验中参与了针对应激、药物线索和中性场景的引导式意象暴露。
与安慰剂-纳曲酮组相比,洛非西定-纳曲酮组患者的阿片类药物戒断率更高,复发结局更好。此外,与安慰剂-纳曲酮组相比,洛非西定-纳曲酮组患者在实验室中的心率显著更低,应激和药物线索诱导的阿片类药物渴求反应也减弱。
尽管是初步研究,但这些发现首次证明了洛非西定在解决人类与应激相关阿片类药物渴求及复发结局方面的潜力。结果还表明,针对药物相关强化(纳曲酮)以及药物寻求中与应激和线索相关方面的联合疗法可能有助于预防成瘾复发。有必要进一步研发洛非西定以解决与应激相关的阿片类药物渴求及复发问题。