Marsden John, Stillwell Garry, James Kirsty, Shearer James, Byford Sarah, Hellier Jennifer, Kelleher Michael, Kelly Joanna, Murphy Caroline, Mitcheson Luke
Addictions Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Lambeth Addictions, South London and Maudsley NHS Mental Health Foundation Trust, London, UK.
Addictions Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Lancet Psychiatry. 2019 May;6(5):391-402. doi: 10.1016/S2215-0366(19)30097-5. Epub 2019 Apr 2.
Opioid use disorder is a chronic, debilitating, and costly disorder that has increased in prevalence in many countries, with an associated sharp rise in mortality. Maintenance opioid agonist therapy is the first-line treatment, but many patients do not stop using illicit or non-prescribed drugs concomitantly. We aimed to test the efficacy and cost-effectiveness of a personalised psychosocial intervention implemented with a toolkit of behaviour-change techniques as an adjunct to opioid agonist therapy.
We did a pragmatic, open-label, randomised controlled trial at a specialist UK National Health Service community addictions clinic in London, UK. Eligible patients were aged 18 years or older, met criteria for opioid or cocaine dependence, or both, in the past 12 months, and voluntarily sought continued oral maintenance opioid agonist therapy, which they had been prescribed for at least 6 weeks. All participants were treatment resistant (ie, had used illicit or non-prescribed opioids or cocaine on one or more days in the past 28 days at study screening, which was verified by positive urine drug screen). Participants were allocated (1:1) by a web-accessed randomisation sequence (stratified by opioid agonist medication, current cocaine use, and current rug use) to receive a personalised psychosocial intervention (comprising a flexible toolkit of psychological-change methods, including contingency management to reinforce abstinence, recovery activities, and clinic attendance) in addition to treatment as usual, or treatment as usual only (control group). The primary outcome was treatment response at 18 weeks, which was defined as abstinence from illicit and non-prescribed opioids and cocaine in the past 28 days, as measured with treatment outcomes profiles and urine drug screening. Taking a societal cost perspective, we did an evaluation of cost-effectiveness with a wide range of willingness-to-pay values for a unit improvement in the probability of treatment response. We also calculated quality-adjusted life-years (QALYs). Efficacy was analysed in a modified-intention-to-treat population, including all participants who were randomly allocated but excluding those who had previously completed the intervention. This trial is registered with ISRCTN, number ISRCTN69313751. The trial is completed.
Between June 7, 2013, and Dec 21, 2015, we randomly allocated 136 participants to the psychosocial intervention group and 137 to the control group. The trial database was locked on April 19, 2017. Three patients (one in the psychosocial intervention group and two in the control group) who were re-randomised in error were excluded from the analysis. 22 (16%) of 135 patients in the psychosocial intervention group had a treatment response, compared with nine (7%) of 135 in the control group (adjusted log odds 1·20 [95% CI 0·01-2·37]; p=0·048). The psychosocial intervention had a higher probability of being cost-effective than treatment as usual. There was a probability range of 47-87% for willingness-to-pay thresholds of £0-1000 for a unit improvement in the probability of treatment response. QALYs were higher in the psychosocial intervention group than in the control group (mean difference 0·048 [95% CI 0·016-0·080]; p=0·004) in adjusted analyses, with 60% and 67% probabilities of cost-effectiveness at the UK National Institute for Health and Care Excellence's willingness-to-pay thresholds of £20 000 and £30 000 per QALY, respectively. The number of adverse events was similar between groups, and no severe adverse events in either group were judged to be treatment related. One participant in the control group was hospitalised with drug-injection-related sepsis and died.
In maintenance opioid agonist therapy, an adjunctive personalised psychosocial intervention in addition to standard therapy was efficacious and cost-effective compared with standard therapy alone at helping treatment-resistant patients abstain from using illicit and non-prescribed opioids and cocaine.
Indivior.
阿片类药物使用障碍是一种慢性、使人衰弱且代价高昂的疾病，在许多国家的患病率都有所上升，死亡率也随之急剧上升。维持性阿片类激动剂疗法是一线治疗方法，但许多患者并未同时停止使用非法或非处方药物。我们旨在测试一种个性化心理社会干预措施的疗效和成本效益，该干预措施通过行为改变技术工具包实施，作为阿片类激动剂疗法的辅助手段。
我们在英国伦敦一家英国国家医疗服务体系（NHS）的专科社区成瘾诊所进行了一项务实、开放标签、随机对照试验。符合条件的患者年龄在18岁及以上，在过去12个月内符合阿片类药物或可卡因依赖或两者皆有的标准，并且自愿寻求持续的口服维持性阿片类激动剂疗法，且已接受该疗法至少6周。所有参与者均对治疗有抵抗性（即，在研究筛查时的过去28天内，有一天或多天使用过非法或非处方阿片类药物或可卡因，这通过尿液药物筛查呈阳性得到证实）。参与者通过网络访问的随机序列（按阿片类激动剂药物、当前可卡因使用情况和当前药物使用情况分层）以1:1的比例分配，除接受常规治疗外，还接受个性化心理社会干预（包括一套灵活的心理改变方法工具包，包括强化禁欲的应急管理、康复活动和门诊就诊），或仅接受常规治疗（对照组）。主要结局是18周时的治疗反应，定义为过去28天内戒除非法和非处方阿片类药物及可卡因，通过治疗结局概况和尿液药物筛查进行测量。从社会成本角度出发，我们对成本效益进行了评估，针对治疗反应概率的单位改善，采用了广泛的支付意愿值范围。我们还计算了质量调整生命年（QALYs）。在改良意向性治疗人群中分析疗效，包括所有随机分配的参与者，但排除那些之前已完成干预的参与者。该试验已在国际标准随机对照试验编号注册库（ISRCTN）注册，编号为ISRCTN69313751。试验已完成。
在2013年6月7日至2015年12月21日期间，我们将136名参与者随机分配至心理社会干预组，137名参与者随机分配至对照组。试验数据库于2017年4月19日锁定。三名因错误重新随机分组的患者（心理社会干预组一名和对照组两名）被排除在分析之外。心理社会干预组135名患者中有22名（16%）有治疗反应，而对照组135名患者中有9名（7%）有治疗反应（调整后的对数比值1.20 [95%置信区间0.01 - 2.37]；p = 0.048）。与单纯常规治疗相比，心理社会干预具有更高的成本效益概率。对于治疗反应概率的单位改善，支付意愿阈值为0至1000英镑时，成本效益概率范围为47%至87%。在调整分析中，心理社会干预组的QALYs高于对照组（平均差异0.048 [95%置信区间0.016 - 0.080]；p = 0.004），在英国国家卫生与保健优化研究所（NICE）每QALY支付意愿阈值为20000英镑和30000英镑时，成本效益概率分别为60%和67%。两组间不良事件数量相似，两组均未判定有严重不良事件与治疗相关。对照组一名参与者因与药物注射相关的败血症住院并死亡。
在维持性阿片类激动剂治疗中，与单独的标准治疗相比，除标准治疗外增加个性化心理社会干预在帮助对治疗有抵抗性的患者戒除非法和非处方阿片类药物及可卡因方面是有效且具有成本效益的。
英迪维亚公司。
