Lalani Elisha, Menon Raakhi, Mufti Mariam A, Kumfa Cecil, Raji Mukaila
Department of Internal Medicine, Division of General Medicine, University of Texas Medical Branch, Galveston, USA.
Department of Internal Medicine, Division of Geriatrics & Palliative Medicine, University of Texas Medical Branch, Galveston, USA.
Cureus. 2023 Aug 20;15(8):e43821. doi: 10.7759/cureus.43821. eCollection 2023 Aug.
Public health efforts to reduce the opioid overdose epidemic and treat opioid use disorder (OUD) have met with challenges associated with current non-standardized approaches to managing opioid withdrawal symptoms, such as itching, jitteriness, anxiety, depression, craving, vomiting, diarrhea, insomnia, and anorexia. These symptoms pose substantial obstacles to the safe initiation of medications for OUD, maintenance of long-term sobriety, and prevention of relapse. In clinical practice, multiple medications (polypharmacy) are prescribed to manage these withdrawal symptoms, including ondansetron and promethazine for vomiting and nausea, loperamide and Lomotil for diarrhea, hydroxyzine and doxepin for pruritus, benzodiazepines, the Z-drugs, and melatonin for insomnia, and benzos, tricyclic antidepressants (TCAs), and various serotonergic agents for anxiety. This polypharmacy is associated with an increased risk of adverse drug-drug interactions and adverse drug events, increased medical costs, and increased odds of medication non-adherence and relapse. We propose an alternative single medication, mirtazapine, a noradrenergic and specific serotonergic receptor antagonist, that can be used for myriad symptoms of opioid withdrawal. Case series, clinical studies, and clinical trials have shown mirtazapine to be effective for treating nausea and vomiting resulting from multiple etiologies, including hyperemesis gravidarum and chemotherapy-induced emesis. Other evidence supports the salutary effects of mirtazapine on itching and craving. Research findings support mirtazapine's beneficial effects on diarrhea and anxiety, a consequence of its modulating effects on serotonergic receptors mediating mood and gastrointestinal symptoms. There is also evidence supporting its efficacy as a potent and non-addictive sleep aid, which presents itself as a solution for insomnia associated with opioid withdrawal. The current review presents evidence from extant literature supporting mirtazapine as a one-drug strategy to treat the variety of symptoms of opioid withdrawal. This one-drug strategy has much potential to decrease polypharmacy, adverse drug events, relapse, and healthcare cost and increase the likelihood of prolonged sobriety and better quality of life for people living with OUD.
为减少阿片类药物过量流行及治疗阿片类药物使用障碍（OUD）所做的公共卫生努力，遇到了与当前管理阿片类药物戒断症状的非标准化方法相关的挑战，这些症状包括瘙痒、神经过敏、焦虑、抑郁、渴望、呕吐、腹泻、失眠和厌食。这些症状对安全启动治疗OUD的药物、维持长期清醒及预防复发构成了重大障碍。在临床实践中，会开具多种药物（联合用药）来管理这些戒断症状，包括用昂丹司琼和异丙嗪治疗呕吐和恶心，用洛哌丁胺和易蒙停治疗腹泻，用羟嗪和多塞平治疗瘙痒，用苯二氮䓬类药物、Z类药物和褪黑素治疗失眠，以及用苯二氮䓬类药物、三环类抗抑郁药（TCA）和各种5-羟色胺能药物治疗焦虑。这种联合用药与药物不良相互作用及不良药物事件的风险增加、医疗成本增加、药物不依从和复发几率增加有关。我们提出一种替代的单一药物——米氮平，一种去甲肾上腺素能和特异性5-羟色胺能受体拮抗剂，可用于治疗阿片类药物戒断的多种症状。病例系列、临床研究和临床试验表明，米氮平对治疗由多种病因引起的恶心和呕吐有效，包括妊娠剧吐和化疗引起的呕吐。其他证据支持米氮平对瘙痒和渴望有有益作用。研究结果支持米氮平对腹泻和焦虑有有益作用，这是其对介导情绪和胃肠道症状的5-羟色胺能受体具有调节作用的结果。也有证据支持其作为一种强效且无成瘾性的助眠药物的疗效，这为与阿片类药物戒断相关的失眠提供了一种解决方案。本综述展示了现有文献中的证据，支持米氮平作为一种单一药物策略来治疗阿片类药物戒断的各种症状。这种单一药物策略有很大潜力减少联合用药、不良药物事件、复发和医疗保健成本，并增加OUD患者长期清醒的可能性和提高生活质量。
