Tinnitus disability is a heterogeneous and complex condition, affecting more than 10% and compromising the quality of life of 2% of the population, with multiple contributors, often unknown, and enigmatic pathophysiology. The available treatment options are unsatisfactory, as they can, at best, reduce tinnitus severity, but not eliminate its perception. Given the spread of tinnitus and the lack of a standardized treatment, it is crucial to understand the economic burden of this condition. We conducted a systematic review of the literature on PubMed/MEDLINE, Embase, the Cochrane Database of Systematic Reviews (CDSR) and Google Scholar, in order to identify all the articles published on the economic burden of tinnitus before 1 April 2021 (PROSPERO—International prospective register of systematic reviews—No: CRD42020180438). Out of 273 articles identified through our search strategy, only five articles from studies conducted in the United States of America (USA), the Netherlands and the United Kingdom (UK) provided data on tinnitus’s economic costs. Three studies provided mean annual estimates per patient ranging between EUR 1544 and EUR 3429 for healthcare costs, between EUR 69 and EUR 115 for patient and family costs and between EUR 2565 and EUR 3702 for indirect costs, including productivity loss. The other two studies reported an annual mean cost of EUR 564 per patient for tinnitus-related clinical visits, and total costs of EUR 1388 and EUR 3725 for patients treated with a sound generator and Neuromonics Tinnitus Treatment, respectively. Our comprehensive review shows a gap in the knowledge about the economic burden of tinnitus on healthcare systems, patients and society. The few available studies show considerable expenses due to healthcare and indirect costs, while out-of-pocket costs appear to be less financially burdensome. Comprehensive health economic evaluations are needed to fill the gaps in current knowledge, using a unified method with reliable and standardized tools.

Several studies show that patients with depression and post-traumatic stress disorder respond with fewer specific autobiographical memories in a cued memory task (i.e. the autobiographical memory test; AMT) compared to healthy controls. One previous study found this phenomenon among tinnitus patients as well (Andersson, Ingerholt, & Jansson, 2003). The aim of this study was to replicate the previous study with an additional control group of depressed patients and memory errors as measured with the AMT as an additional outcome. We included 20 normal hearing tinnitus patients, 20 healthy controls and 20 persons diagnosed with clinical depression. The AMT was administered together with self-report measures of depression, anxiety and tinnitus distress. Both the tinnitus and depression groups differed from the healthy control group in that they reported fewer specific autobiographical memories. There were, however, differences between the tinnitus and depression groups in terms of the errors made on the AMT. The depression group had more overgeneral memories than the normal control group, whereas the tinnitus group did not differ from the control group on this memory error. The tinnitus group had more semantic associations and non-memories than the other two groups, suggesting that executive functioning may play a role for the tinnitus group when completing the AMT. Clinical and theoretical implications of the findings are discussed.

Tinnitus (the perception of sound in the absence of any corresponding external source) is highly prevalent and can be distressing. There are unanswered questions about how tinnitus, suicidal thoughts, and suicidal behaviours co-occur and interact. To establish the extent of scientific literature, this scoping review catalogued primary reports addressing the associations between tinnitus, suicidal ideation, attempted suicide, and death by suicide. We searched OvidSP, Medline, EMBASE, PsycINFO, CINAHL, Google Scholar, EThoS, and ProQuest for all studies and case reports on ideation and/or attempted and/or completed suicide in the context of tinnitus. Twenty-three studies were included, and data were charted according to study type. Several epidemiological and other observational studies gave evidence of risk factors and an association between suicidal ideation, suicidal behaviour, and tinnitus. However, there was no evidence of the direction of causality. Qualitative studies are indicated to explore the patient’s experience and understand the dynamics of any interaction between tinnitus and suicidal thoughts and behaviours. A theory-informed model of tinnitus and suicide needs to be developed to inform the development of interventions and how tinnitus patients are supported clinically.

Objectives: Tinnitus is the perception of sound without an external source, affecting quality of life that can cause severe distress in approximately 1 to 3% of the population of people with tinnitus. Randomized controlled trials of cognitive behavioral therapy for tinnitus have demonstrated its effectiveness in improving quality of life, but the effects of their implementation on a large scale in routine practice remains unknown. Therefore, the main purpose of this study was to examine the effects of stepped-care cognitive behavioral therapy for tinnitus delivered in a tertiary audiological center of a regional hospital. Second, we wished to examine predictors of favorable outcome. Design: Four hundred three adults with chronic tinnitus were enrolled in this prospective observational study (at 3 months, N=334, 8 months, N=261; 12 months, N=214). The primary outcome was health-related quality of life as measured by the Health Utilities Index III (HUI-III) at 12 months. Secondary outcomes were self-reported levels of tinnitus-related distress, disability, affective distress and tinnitus-related negative beliefs and fear. Measures were completed pre-intervention at 3 months, 8 months, and 12 months. Multilevel modeling was used to examine effects and their predictors. Results: Younger participants with lower levels of tinnitus distress were more likely to dropout while those with higher tinnitus distress at baseline and quality of life were more likely to receive step 2 of treatment. MLM analyses revealed, with one exception, no relation between any baseline variable and outcome change over time. Most participants’ improvement exceeded minimally clinical important difference criteria for quality of life, tinnitus-related handicap, and tinnitus distress. Conclusions: Results from this large pragmatic study complements those from randomized controlled trials of cognitive behavioral therapy for chronic tinnitus distress and supports its implementation under “real-world” conditions.

Tinnitus is associated with a variety of aetiologies, phenotypes, and underlying pathophysiological mechanisms, and available treatments have limited efficacy. A combination of treatments, addressing various aspects of tinnitus, might provide a viable and superior treatment strategy. In this international multicentre, parallel-arm, superiority, randomised controlled trial, patients with chronic subjective tinnitus were recruited from five clinical sites across the EU as part of the interdisciplinary collaborative UNITI project. Patients were randomly assigned using a web-based system, stratified by their hearing and distress level, to single or combination treatment of 12 weeks. Cognitive-behavioural therapy, hearing aids, structured counselling, and sound therapy were administered either alone or as a combination of two treatments resulting in ten treatment arms. The primary outcome was the difference in the change from baseline to week 12 in the total score of the Tinnitus Handicap Inventory (THI) between single and combination treatments in the intention-to-treat population. All statistical analysis were performed blinded to treatment allocation. 674 patients of both sexes aged between 18 and 80 years were screened for eligibility. 461 participants (190 females) with chronic subjective tinnitus and at least mild tinnitus handicap were enrolled, 230 of which were randomly assigned to single and 231 to combination treatment. Least-squares mean changes from baseline to week 12 were -11.7 for single treatment (95% confidence interval [CI], -14.4 to -9.0) and -14.9 for combination treatments (95% CI, -17.7 to -12.1), with a statistically significant group difference ( p =0.034). Cognitive-behavioural therapy and hearing aids alone had large effect sizes, which could not be further increased by combination treatment. No serious adverse events occurred. In this trial involving patients with chronic tinnitus, all treatment arms showed improvement in THI scores from baseline to week 12. Combination treatments showed a stronger clinical effect than single treatment, however, no clear synergistic effect was observed when combining treatments. We observed rather a compensatory effect, where a more effective treatment offsets the clinical effects of a less effective treatment. ClinicalTrials.gov Identifier: NCT04663828 .

The genetic basis underlying the co-occurrence of tinnitus and mild cognitive impairment (MCI) remains unknown. Adults with chronic tinnitus from a European cohort were classified into MCI (n=75) and non-MCI (n=201) groups, and rare variant distributions were assessed using gene burden analyses. Approximately one-fourth of individuals with chronic tinnitus exhibited MCI in their early fifties. Rare loss-of-function variants in PRKRA were identified in 18.6% of MCI patients, including a recurrent ∼3kb deletion in 14 individuals (OR=513.86, 95% CI [224.34-1177.02], adjusted p -value = 1.04E-48). These carriers reported tinnitus onset approximately eight years before MCI was observed. Cognitive impairment was linked to tinnitus, but not to hyperacusis or high-frequency hearing loss, among carriers of rare variants in MCI candidate genes, particularly PRKRA. The association between PRKRA variants and MCI was independent of APOE ε4 allele and known Parkinson’s disease dementia risk variants. In silico modelling and docking show increased binding affinity between mutant PACT ( PRKRA ) and PKR, suggesting over-activation of the PKR-eIF2α integrated stress response. Functional validation using a PRKRA knockout model identified differentially expressed genes enriched in dementia-related pathways. These findings support PRKRA as a potential driver gene in tinnitus-associated MCI. Clinicaltrial.gov: NCT04663828