Introduction
Tinnitus is defined as a non-observable, self-reported auditory phantom phenomenon with patients internally perceiving a sound without a corresponding external sound source [1, 2]. Tinnitus affects ~50 million adults in the United States, the prevalence ranging from 4.6 to 32.9 % in the world [3–5]. Subjective loudness, quality, and awareness of tinnitus sounds varies widely, leading to varied degrees of annoyance, ranging from slight annoyance to severe distress [6–8]. In 20% of the cases, tinnitus causes distress that manifests as annoyance, anxiety, insomnia, problems of concentration, and depression [9].
Major depressive disorder [MDD] is a psychiatric illness with feelings of sadness, guilt, hopelessness, and worthlessness, followed by a high probability of suicide [10]. It is recurrent, disabling, and widely prevalent with estimated lifetime prevalence of 20%. It is also a leading cause of disability and mortality in the world [11]. Although recognized as the leading cause of disease burden worldwide, the actual pathogenesis of MDD remains unknown [10, 11].
One study proposed the term “tinnitus disorder” defined as tinnitus with associated sufferings, including emotional distress, cognitive dysfunction, and/or autonomic arousal, leading to behavioral changes and functional disability [12]. In clinical practice, it is often difficult to identify whether higher tinnitus distress leads to a depressive mood or vice versa. Tinnitus and MDD may share common symptoms and risk factors, such as chronic health problems, lower socioeconomic status, and higher perceived stress levels [13]. MDD is also potentially related to tinnitus due to the similarity of pathophysiology [14, 15]. The literature shows findings that tinnitus sufferers often have a comorbid depression; however, a causal relationship and direction of causation remain uncertain because of cross-sectional study designs and use of self-reported data from surveys in these studies [13, 16–19]. Recently, some investigators have reported that tinnitus may be a trigger factor in depression, whereas others have indicated that the association between depression and tinnitus may be bidirectional, rather than unidirectional [14, 16]. Nonetheless, to our knowledge, no population-based studies have investigated the association between tinnitus and subsequent MDD.
This study aimed to investigate the relationship between tinnitus and MDD using a large, population-based dataset in Taiwan by studying the incidence of both entities.
Methods
Database
We obtained data on the study population from Taiwan's National Health Insurance Research Database [NHIRD], which is maintained and regulated by the Data Science Center of the Ministry of Health and Welfare of Taiwan. The NHIRD was established in 1995 and covers more than 99.6% of all 23 million-plus citizens. The NHIRD includes data on registries of contracted medical facilities and beneficiaries, and claims submitted for reimbursement. Taiwan's NHI program covers virtually everything, including preventive care, cancer screenings, mental health, general primary care, and in-hospital care. The NHIRD provides a unique opportunity for scientists in Taiwan to investigate the association between tinnitus and the subsequent occurrence of major depressive disorder. The study was approved by the Institutional Review Board of Taipei Medical University [TMU-JIRB N202109059]. Since we used an administrative claim dataset to analyze data, patient informed consent was waived.
Study Sample
We designed this study as an observational cohort study. We established the study cohort by identifying 393,761 patients aged ≥ 20 years who received their first diagnosis of tinnitus [ICD-9-CM code 388.3 or ICD-10-CM codes H93.1, H93.11, H93.12, H93.13, or H93.19] at outpatient facilities [doctor's offices or outpatient departments of hospitals] between January 1, 2014 and December 31, 2016. We defined the date of their first-time diagnosis of tinnitus as their index date. We excluded 18,489 patients who had received a diagnosis of major depressive disorder [ICD-9-CM codes 296.20–296.26, 296.30–296.36, 296.82, and 300.4 or ICD-10-CM code F33] or bipolar disorder within 3 years prior to the index date. Ultimately, the selected study cohort included 375,272 patients with tinnitus.
We likewise retrieved patients of a comparison cohort from the registry of beneficiaries included in the NHIRD. After excluding patients aged