The Yale Stress Center, Yale University School of Medicine, New Haven, Connecticut.
Doctoral Program in Clinical Psychology, Albizu University, Doral, Florida.
Am J Addict. 2019 Nov;28(6):480-488. doi: 10.1111/ajad.12942. Epub 2019 Aug 26.
Lofexidine (LFX), an α2A adrenergic receptor agonist, known to alleviate opioid withdrawal symptoms, was assessed in combination with oral naltrexone (NTX) for effects on opioid use outcomes and NTX treatment compliance.
Detoxified individuals (ages 18-55, 80% male) with opioid use disorder Diagnostic and Statistical Manual of Mental Disorders, 4th edition were randomized to 2.4 mg/day of LFX (n = 26) or Placebo (PBO, n = 31) in a double-blind manner for 12 weeks of treatment. NTX compliance, opioid-free urine samples, opioid craving as well as vital signs, subjective opioid withdrawal symptoms were assessed.
Intent to treat analysis revealed significantly better control over opioid craving in the LFX/NTX vs PBO/NTX group (P < .03), but no differences between groups in NTX compliance, opioid use, and overall opioid craving. However, subject withdrawal due to medication intolerance was significantly higher in the LFX/NTX (5/26) vs PBO/NTX (0/31) (P < .01). Two additional patients were withdrawn due to acute hepatitis infection. Post hoc secondary analyses with the nonwithdrawn sample indicated significantly higher rates of treatment completion (P < .05) and NTX compliance (P < .01), lower percent opioid urine samples (P < .05), and lower overall opioid craving (P < .05) in the LFX/NTX vs the PBO/NTX group.
Although preliminary, these findings suggest that LFX at doses up to 2.4 mg/daily was safe and improved control over opioid cravings. Among those who tolerated the medication, LFX/NTX significantly improved the opioid craving, delayed return to opioid use, and improved treatment compliance and completion rates. These findings support further assessment of LFX dose titration schedule along with the adjunctive use of LFX with NTX treatment to enhance opioid relapse prevention. (Am J Addict 2019;00:1-9).
可乐定（LFX）是一种α2A 肾上腺素能受体激动剂，已知可缓解阿片类药物戒断症状，本研究评估了 LFX 联合口服纳曲酮（NTX）对阿片类药物使用结果和 NTX 治疗依从性的影响。
纳入符合 DSM-IV 阿片类使用障碍诊断标准的已戒毒个体（年龄 18-55 岁，80%为男性），并将其随机分配至 2.4mg/d 的 LFX 组（n=26）或安慰剂（PBO，n=31），进行为期 12 周的双盲治疗。评估纳曲酮的依从性、阿片类药物阴性尿液样本、阿片类药物渴求以及生命体征、主观阿片类药物戒断症状。
意向治疗分析显示，LFX/NTX 组在控制阿片类药物渴求方面明显优于 PBO/NTX 组（P<.03），但两组在纳曲酮的依从性、阿片类药物使用和总体阿片类药物渴求方面无差异。然而，LFX/NTX 组（5/26）因药物不耐受而导致的停药率明显高于 PBO/NTX 组（0/31）（P<.01）。另有 2 名患者因急性肝炎感染而停药。进一步对未停药的患者进行亚组分析显示，LFX/NTX 组的治疗完成率（P<.05）和纳曲酮的依从性（P<.01）显著较高，阿片类药物尿液样本的百分比（P<.05）和总体阿片类药物渴求（P<.05）较低。
尽管这是初步结果，但这些发现表明，最高达 2.4mg/d 的可乐定剂量是安全的，并且可以改善对阿片类药物渴求的控制。在耐受药物的患者中，LFX/NTX 显著改善了阿片类药物渴求，延迟了阿片类药物的复吸，提高了治疗的依从性和完成率。这些发现支持进一步评估 LFX 剂量滴定方案以及将 LFX 与 NTX 联合辅助治疗，以增强阿片类药物戒断预防。（美国成瘾杂志 2019；00:1-9）。
