Growing evidence from pharmacovigilance data and postmortem toxicology reports highlights the misuse potential of gabapentinoids. This study aimed to investigate the risk of serious adverse outcomes (drug misuse, overdose, major trauma), and their risk factors, in primary care patients who are prescribed gabapentinoids. Using the UK Clinical Practice Research Datalink, a matched cohort study calculated adverse event rates separately for gabapentinoid-exposed and unexposed cohorts. In the exposed cohort, event rates for exposure to a range of potential risk factors were calculated. Event rates were compared using Cox proportional hazards models, adjusted for age, sex, deprivation, previous mental health diagnosis, and coprescribing with potentially interacting medicines. Substance misuse (gabapentin adjusted hazard ratio [95% CI]: 2.40 [2.25-2.55]), overdose (2.99 [2.56-3.49]), and major trauma (0-2.5 years: 1.35 [1.28-1.42]; 2.5 to 10 years: 1.73 [1.56-1.95]) were more common among patients prescribed gabapentinoids than matched individuals who were not. The association with overdose was stronger for pregabalin than gabapentin. All adverse outcomes were significantly associated with smoking, history of substance misuse, overdose, or a mental health condition and prescription of opioids, benzodiazepines, antidepressants, and Z-drug hypnotics (eg, gabapentin hazard ratios for association of concurrent opioid use: misuse 1.49 [1.47-1.51]; overdose 1.87 [1.78-1.96]; major trauma 1.28 [1.26-1.30]). Our findings highlight the importance of careful patient selection when prescribing gabapentinoids and the need to educate prescribers about the risks of these drugs, particularly in combination with other central nervous system depressants.

中文翻译：

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使用临床实践研究数据链：一项队列研究，加巴喷丁治疗期间不良后果的风险以及与英国初级保健风险增加相关的因素。

药物警戒数据和尸检毒理学报告中越来越多的证据凸显了加巴喷丁类药物的滥用潜力。本研究旨在调查服用加巴喷丁类药物的初级保健患者发生严重不良后果（药物滥用、用药过量、重大创伤）的风险及其危险因素。使用英国临床实践研究数据链，一项匹配队列研究分别计算了加巴喷丁暴露组和未暴露组的不良事件发生率。在暴露队列中，计算了暴露于一系列潜在危险因素的事件率。使用 Cox 比例风险模型比较事件发生率，并根据年龄、性别、贫困、先前的心理健康诊断以及与潜在相互作用的药物的共同处方进行调整。药物滥用（加巴喷丁调整后的风险比 [95% CI]：2.40 [2.25-2.55]）、用药过量（2.99 [2.56-3.49]）和重大创伤（0-2.5 岁：1.35 [1.28-1.42]；2.5 至 10年：1.73 [1.56-1.95]）在服用加巴喷丁类药物的患者中比未服用加巴喷丁类药物的匹配个体更常见。普瑞巴林与药物过量的相关性比加巴喷丁更强。所有不良结果均与吸烟、药物滥用史、用药过量或精神健康状况以及阿片类药物、苯二氮卓类药物、抗抑郁药和 Z-药物安眠药处方显着相关（例如，加巴喷丁与同时使用阿片类药物相关的风险比：滥用 1.49 [1.47-1.51]；过量1.87[1.78-1.96]；重大创伤1.28[1.26-1.30]）。我们的研究结果强调了在开加巴喷丁类药物处方时仔细选择患者的重要性，以及需要教育处方者了解这些药物的风险，特别是与其他中枢神经系统抑制剂联合使用时。