Division of Epidemiology and Public Health, School of Community Health Sciences, Nottingham City Hospital, University of Nottingham, Clinical Sciences Building, Nottingham, NG5 1PB, UK.
Cancer Causes Control. 2012 Dec;23(12):1959-64. doi: 10.1007/s10552-012-0073-0. Epub 2012 Oct 12.
Tricyclic antidepressants have been demonstrated in the laboratory to have anticancer properties. A recent study by our group also suggested a protective effect against development of colorectal cancer and glioma. This study aims to determine whether the anticancer action of tricyclics translates to improved survival in these cancers post-diagnosis.
A study using the General Practice Research Database examined whether tricyclic antidepressant exposure in the months following diagnosis of glioma or colorectal cancer would affect longer term all-cause mortality. Cox proportional hazards modelling adjusted for age, gender, smoking, body mass index, comorbidity, and diagnosed depression.
A cohort of 1,364 glioma and 16,519 colorectal cancer patients were identified. There was a non-significant reduction in the hazard for glioma patients treated with tricyclics (HR = 0.83, CI = 0.53-1.30). This was mainly found in patients who were not previously exposed to tricyclics (HR = 0.56, CI = 0.26-1.18). In contrast, a significant increase in hazard was found for colorectal cancer (HR = 1.37, CI = 1.21-1.54). This was mostly in patients prescribed low-dose tricyclics (HR = 1.57, CI = 1.33-1.86).
We have shown no significant mortality reduction in colorectal cancer or glioma patients treated with tricyclics. An apparent detrimental effect observed in colorectal cancer may be related to prescription of low-dose tricyclics in the management of pain related to disseminated cancer. We cannot rule out small effects or an effect that occurs exclusively at higher doses. Blinded clinical studies may therefore be the only method of determining efficacy in glioma patients.
三环类抗抑郁药已在实验室中证明具有抗癌特性。我们小组最近的一项研究还表明，它们对结直肠癌和神经胶质瘤的发展具有保护作用。本研究旨在确定三环类药物的抗癌作用是否转化为这些癌症确诊后的生存改善。
一项使用普通实践研究数据库的研究调查了在诊断出神经胶质瘤或结直肠癌后的几个月内接触三环类抗抑郁药是否会影响长期全因死亡率。Cox 比例风险模型调整了年龄、性别、吸烟、体重指数、合并症和诊断出的抑郁症。
确定了 1364 名神经胶质瘤和 16519 名结直肠癌患者的队列。接受三环类药物治疗的神经胶质瘤患者的风险呈非显著降低（HR = 0.83，CI = 0.53-1.30）。这主要是在以前未接触过三环类药物的患者中发现的（HR = 0.56，CI = 0.26-1.18）。相比之下，结直肠癌患者的风险显著增加（HR = 1.37，CI = 1.21-1.54）。这主要是在低剂量三环类药物处方的患者中发现的（HR = 1.57，CI = 1.33-1.86）。
我们没有发现接受三环类药物治疗的结直肠癌或神经胶质瘤患者的死亡率有显著降低。在结直肠癌中观察到的明显不利影响可能与低剂量三环类药物用于治疗转移性癌症相关疼痛的管理有关。我们不能排除较小的影响或仅在较高剂量下发生的影响。因此，盲法临床试验可能是确定神经胶质瘤患者疗效的唯一方法。
