Use of Antidepressants and Risk of Cutaneous Melanoma: A Prospective Registry-Based Case-Control Study

Abstract

Purpose

Melanoma is the cancer with the most rapidly rising incidence rate in Norway. Although exposure to ultraviolet radiation (UVR) is the major environmental risk factor, other factors may also contribute. Antidepressants have cancer inhibiting and promoting side effects, and their prescription rates have increased in parallel with melanoma incidence. Thus, we aimed to prospectively examine the association between use of antidepressants and melanoma by using nation-wide data from the Cancer Registry of Norway, the National Registry, the Norwegian Prescription Database and the Medical Birth Registry of Norway.

Patient and Methods

All cases aged 18–85 with a primary cutaneous invasive melanoma diagnosed during 2007–2015 (n=12,099) were matched to population controls 1:10 (n=118,467) by sex and year of birth using risk-set sampling. We obtained information on prescribed antidepressants and other potentially confounding drug use (2004–2015). Conditional logistic regression was used to estimate adjusted rate ratios (RRs) and 95% confidence intervals (CIs) for the association between overall and class-specific use of antidepressants and incident melanoma.

Results

Compared with ≤1 prescription, ≥8 prescriptions of antidepressants overall were negatively associated with melanoma (RR 0.81 CI 0.75–0.87). Class-specific analyses showed decreased RRs for selective serotonin reuptake inhibitors (RR 0.82 CI 0.73–0.93) and mixed antidepressants (RR 0.77 CI 0.69–0.86). The negative association was found for both sexes, age ≥50 years, residential regions with medium and highest ambient UVR exposure, all histological subtypes, trunk, upper and lower limb sites and local disease.

Conclusion

Use of antidepressants was associated with decreased risk of melanoma. There are at least two possible explanations for our results; cancer-inhibiting actions induced by the drug and less UVR exposure among the most frequent users of antidepressants.

Keywords:

• antidepressants
• melanoma
• prescription drugs
• pharmacoepidemiology
• registry-based

Abbreviations

All are defined in full at their first instance in the text: ATC, anatomical therapeutic chemical; CI, confidence interval; CRN, Cancer Registry of Norway; DDD, defined daily doses; ICD-O-3, International Classification of Diseases of Oncology 3rd edition; ICD-7/10, International Classification of Diseases 7th/10th Revision; NM, nodular melanoma; NorPD, Norwegian Prescription Database; PIN, personal identification number; RR, rate ratio; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressants; UVR, ultraviolet radiation.

Ethics Approval and Informed Consent

The study is approved by the Norwegian Data Protection Authority and the Regional Committee for Medical and Health Research Ethics. The study is also approved by the national registries contributing with data; CRN, the National Registry, NorPD and the Medical Birth Registry. The linkage key for the 11-digit PINs was stored and governed by a third party unavailable to the research team. All data management and analyses were conducted on data with no individual person identified. This case-control study utilized only data from nationwide population-based registers and thus did not include a recruitment process for patients, who were not involved in neither the design nor conduct of the study. Thus, the research question and outcome measures were not informed by any specific patient priorities, experiences or preferences. Rather, their formulation was based upon our own priorities for patient benefit and result interpretation. All results are distributed on a group level, without any possibilities for individual identification.

Data Sharing Statement

The data is available as presented in the paper. According to Norwegian legislation, our approvals to use the data for the current study do not allow us to distribute or make the data directly available to other parties.

Author Contributions

All authors contributed to data analysis, drafting and revising the article, gave final approval of the version to be published, and agreed to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

The study is funded by the South-Eastern Norway Regional Health Authority (no. 16/00451-33).