Prevalence of Generalized Anxiety Disorder in Japan | NDT

Table 2 The Degree of Coincidence Between the Diagnosis of GAD by GAD-7 Score and DSM-5

The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the GAD-7 diagnosis to the DSM diagnosis were 58%, 96%, 45%, and 97%, respectively. Notably, the proportion of participants qualifying for the DSM-5 criteria for GAD was related to their GAD-7 scores. Among the participants with GAD-7 scores of 0–4, 5–9, 10–14, and 15–21, 0.7%, 12.7%, 35.6%, and 63.3%, respectively, met the DSM-5 criteria for GAD. Thus, the proportion of participants who met the DSM-5 criteria for GAD increased with higher GAD-7 scores.

QOL of the Probable GAD Patients

QOL scores were significantly lower among the probable GAD patients (GAD-7 score of ≥10) than among those with GAD-7 score of pTable 3). Based on subscales analysis, “pain/discomfort” (median, probable GAD patients: 2, without GAD: 1) and “anxiety/depression” (median, probable GAD patients: 3, without GAD: 1) were the most serious issues for the probable GAD patients.

Table 3 QOL of the Study Participants, Stratified by GAD-7 Levels

QOL Among Participants Qualifying for Both GAD-7 and DSM-5

In this study, 694 participants met the GAD criteria both as per GAD-7 and DSM-5. The EQ-5D-5L index value and EQ VAS among those who met both GAD-7 and DMS-5 criteria were substantially lower than those qualifying for only one criterion (Table 4).

Table 4 QOL of Participants by GAD Status Based on Degree of Coincidence with GAD-7 and DSM-5 Diagnostic Criteria

Healthcare-Seeking Behavior for Anxiety or Other Mental Issues

Of the 1530 probable GAD patients, 51.2% had “never visited a medical institution” for anxiety or other mental issues, 27.6% were “currently visiting one”, and 21.2% had “visited before, but not now”. Of those who had visited healthcare institutions for anxiety or other mental issues (n=747), the majority (81.0%) had seen specialists (psychiatrists, psychosomatic medicine doctors) and 18.1% had seen internists. The participants visited healthcare institutions because “my symptoms were severe” (54.1%), “my symptoms made daily life difficult” (52.6%), “a friend or family member recommended it” (23.7%), and “found out about it on the internet” (17.1%) (Supplementary Table 2).

Status of Disease Recognition Among the Probable GAD Patients

Disease Awareness

Among the probable GAD patient group, 76.5% had never heard of the disease “generalized anxiety disorder” or GAD. On the other hand, only 3.9% knew details about the characteristics of the disease and treatment, 11.8% had a rough idea about what kind of a disease it is, and 7.9% had only heard about the disease name. Among the probable GAD patients who recognized the disease of GAD (n=360), the main routes of information acquisition for disease-aware patients were: “looked it up on my own” (41.1%), “happened to hear the name of the disease” (26.9%), and “heard it from a medical professional” (23.9%) (Supplementary Table 2).

Motivation to Receive Treatment

Among the probable GAD patients, 61.4% wished to receive treatment for the problem and the remaining 38.6% did not feel the necessity (Supplementary Table 2).

Understanding of the Underlying Cause of GAD

Among the probable GAD patient group, 46.3% thought “it is a personality” and 31.3% thought “it is a disease”, 11.0% thought “it is neither personality-related, nor a disease”, while the remaining 11.3% was “not sure” (Supplementary Table 2).

History/Family History of Mental Disorders and Comorbidities

Among the probable GAD patients, 26.9% reported a history of a diagnosis of depression. This was followed by 8.8% with panic disorder and 5.4% with social anxiety disorder. On the other hand, only 4.0% had a history of GAD diagnosis (Figure 1). Among the blood relatives of probable GAD patients, 18.2% had been diagnosed with depression; 4.7% with panic disorder; and 1.7% with social anxiety disorder, while only 1.4% mentioned a past diagnosis of GAD (Supplementary Table 3). Among those with probable GAD, circulation (25.0%), gastroenterology (18.1%), nephrology, urology, and gynecology (18.0%), and skin (18.0%) were the most commonly affected systems (Supplementary Table 4). Specifically reflux esophagitis, irritable bowel syndrome, migraine headaches, and neuralgia were more frequently diagnosed among the probable GAD patients (data not shown).

Figure 1 History of mental disorders among probable GAD patients (n=1530). Abbreviation: GAD, generalized anxiety disorder.

Discussion

This web-based, cross-sectional online survey related to GAD among the general population in the Japanese setting provides relevant data on the prevalence of GAD, QOL of the probable GAD patients, their health-seeking behaviors, and the overall recognition/awareness of the disorder.

The proportion of participants with a GAD-7 score of ≥10 (probable GAD patient group) was 7.6%. The results of the study using GAD-7, a simple screening tool, suggested a high prevalence of potential GAD patients, although it is unclear if all need to receive treatment. Moreover, the prevalence of GAD based on the DSM-5 criteria was 6.0%. The 7.6% prevalence of the probable GAD patient group was high compared to previous studies,5 including those conducted in Japan.^9,10 The results may have been influenced by the coronavirus diseases (COVID-19), as the advent of the COVID-19 pandemic led to an increase in cases of depression and anxiety.^23,24 Indeed, in a recent online cross-sectional survey from Mainland China, a high prevalence of anxiety (approximately 45%) was seen in working-age adults in March 2020.²⁴ We found a lower prevalence of GAD in persons ≥65 years of age compared to participants ≤30 years of age. Interestingly, a similar pattern was observed in the previous World Mental Health Survey study⁵ and an Australian National Survey of Mental Health and Well-Being.²⁵ Moreover, as reported previously,²⁵ we found that the working-age population showed a relatively high prevalence of GAD.

Also, regarding family members living together, the probable GAD patients were less likely to live with their spouse or children compared to the non-GAD group. This suggests that being single is associated with having GAD, as previously reported.²⁶

Here, the sensitivity and specificity analyses showed that a GAD-7 cutoff score of ≥10 led to high specificity (96%) and NPV (97%), but poor sensitivity (58%) and PPV (45%). The trade-off between sensitivity/specificity and PPV/NPV is well known, while researchers try to find an optimal balance to maximize the area under the receiver operating characteristic curve. In this study, the sensitivity and specificity of GAD-7 were not optimally balanced, when using DSM-5 criteria as a gold standard. Our findings were contrary to those of Spitzer et al and Muramatsu et al who showed good sensitivity and specificity (both >80%) with GAD-7 cutoff score of ≥10 with diagnosis by mental health professionals using DSM-IV criteria as a gold standard.^18,19 The differences may be attributable to the nature of our study; meeting DSM-5 diagnostic criteria was not based on a physician’s diagnosis, but on self-report. Nevertheless, the high specificity and NPV values may still be useful to rule out GAD in patients with GAD-7 scores of

Furthermore, our results showed that the QOL of the probable GAD patients was lower than that of those without GAD, implying that GAD poses a considerable humanistic burden. The more severe the disease, the worse the QOL. Moreover, many of the probable GAD patients reported not seeking healthcare from medical institutions. Survey findings suggested that patients sought medical help only when symptoms were severe and made daily life difficult. Based on EQ-5D-5L analysis, the more serious issues for the participants with probable GAD were “anxiety/depression” and “pain/discomfort”. These findings also suggested that people with higher GAD-7 scores should consult specialists as a priority to improve their QOL and to determine the necessary treatment.

Surprisingly, the recognition of GAD seems to be extremely low even among probable GAD patients. This seems to be due to a lost opportunity to increase awareness about the disease among patients and families when they visit the physicians. It highlights the need for change in the practice of physicians where they should educate the patients and families about the disease at diagnosis and follow-up visits. While the understanding of GAD was low, many patients wished to receive treatment for their symptoms. This suggests that an opportunity for the successful treatment of patients with GAD presumably exists due to the favorable attitude towards receiving treatment and indicates the need for increasing disease awareness in the general population.

Among the probable GAD patients, many thought that anxiety was not a disease and that their problem stemmed from their own personality, which must have resulted in low healthcare-seeking behavior, further resulting in a lack of motivation for seeking diagnosis and treatment.

Only 4.0% amongst probable GAD patients were diagnosed with GAD in the past while a substantial proportion of patients were diagnosed with other mental disorders, such as depression, panic disorder, and social anxiety disorder. This finding is in line with the previous World Mental Health Survey study wherein mood and anxiety disorders were noted as common comorbidities.⁵ This suggests that GAD patients may be frequently diagnosed with other mental disorders or have other mental disorders as comorbidities and received treatment for them. Regarding underlying diseases other than mental disorder, probable GAD patients were likely to have symptoms of autonomic dysfunction. Furthermore, the symptoms often overlap with those of GAD. Therefore, it is important to note that patients who have diseases with autonomic dysfunction may also have GAD as a comorbidity.

This study’s strength lies in its comprehensive approach, featuring a large sample size and including diagnosed patients and the general population. It explored the prevalence and characteristics of GAD in Japan, capturing potential cases within the broader community. With a web-based survey of 20,009 participants and a questionnaire in Japanese, it gathered diverse perspectives on GAD. Integrating diagnostic criteria-based assessments and validated screening tools like the GAD-7, the study provided a robust estimation of GAD prevalence, highlighting symptom patterns and demographic variations. Examination of QOL using measures like EQ-5D-5L and EQ VAS revealed GAD’s profound impact. The study also illuminated healthcare utilization patterns and GAD awareness levels.

Overall, the prevalence of probable GAD patients was high and most of them had never heard of the disease. Therefore, attempts should also be made to educate the general population about GAD, to increase the level of recognition and understanding regarding the disease among probable GAD patients, and for such patients to see a specialist to improve their QOL. Some of these gaps may be filled by country-level guidelines for diagnosis and treatment of GAD management, which are currently unavailable in Japan. This study contributes to understanding the facts surrounding real-world probable GAD patients and factors that may be contributing to the lower diagnosis rate.

Limitations

This online survey using web-based questionnaire may be limited by selection bias as views are reflective of only those individuals in Japan who can use the internet and computers. As the study included only those volunteering to respond, the findings are limited by response bias including early vs late bias. The possibility of common method bias cannot be denied, though we had adopted methodology so that the respondents would not be able to predict the details of the survey content at the earlier stages. Diagnoses and medications were self-reported by participants using GAD-7 scores and the DSM-5 diagnostic criteria and not by reference to physician confirmation. Responses by study participants to the screening tool and diagnostic criteria were subjective, results of which may not lead to a definitive diagnosis of GAD. The comorbidities were also self-reported and not assessed based on the health system records. With patient-reported data, the study results are subject to recall bias as well as desirability bias. As the study included only Japanese participants, generalizability to other countries would be limited.

Conclusion

This study assessed the prevalence of GAD among the general population in the Japanese setting using a GAD-7 questionnaire. The study also estimated the QOL, the behaviors of visiting medical institutions, as well as the recognition/awareness of the disorder in probable GAD patients. This study revealed that most probable GAD patients were unaware of GAD, only 4.0% were diagnosed with GAD and a substantial proportion was diagnosed with other mental disorders. These results suggest an iceberg phenomenon with low recognition of the symptoms, delayed health-seeking, possible misdiagnoses or missed diagnoses in patients with comorbid mental disorders and missed treatment opportunities. The GAD-7 scale considerably enhances the efficiency of screening for and monitoring anxiety which provides an opportunity to improve the mental health of patients by early identification of patients who may benefit from pharmacologic or psychotherapeutic treatment. Survey results indicate a requirement for creating awareness about GAD among the general population in Japan by disease education; additionally, these findings also highlight a need for the development of clinical guidelines on GAD diagnosis and treatment in Japan so that physicians can appropriately manage GAD and easily educate their patients.

Abbreviations

DSM-5, Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; EQ VAS, EuroQol Visual Analog Scale; EQ-5D-5L, EuroQol 5 dimensions 5-level; GAD-7, generalized anxiety disorder 7-item; GAD, generalized anxiety disorder; NPV, negative predictive value; PPV, positive predictive value; QOL, quality of life; SD, standard deviation; URL, uniform resource locator.

Data Sharing Statement

The data that support the findings of this study are available from Viatris Inc., but restrictions apply to the availability of these data, and so are not publicly available. Data are, however, available from the authors upon reasonable request and with the permission of Viatris Inc.

Acknowledgments

Medical writing and editorial assistance were provided by Padma Singu and Vidula Bhole of MedPro Clinical Research with funding from Viatris Pharmaceuticals Japan Inc. The authors would like to thank Haruhiko Seki, INTAGE Healthcare Inc, for coordinating the study.

Author Contributions

All authors made a significant contribution to the work reported, whether in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Funding

This work was supported by Viatris Pharmaceuticals Japan Inc.

Disclosure

Satoshi Matsuyama, Keisuke Nomoto, and Shingo Higa are full-time employees of Viatris Pharmaceuticals Japan Inc. Tempei Otsubo has received lecture fees from Viatris Pharmaceuticals Japan Inc.; Takeda Pharmaceutical Co., Ltd.; Otsuka Pharmaceutical; Sumitomo Pharma Co., Ltd.; YoshitomiYakuhin; Mochida; Meiji Seika Pharma Co., Ltd.; Kyowa Pharmaceutical; Lundbeck Japan; and IQVIA. Osamu Takashio reported honoraria for lectures from Viatris Pharmaceuticals Japan Inc.; Meiji Seika Pharma Co., Ltd.; Takeda Pharmaceutical Co., Ltd.; Sumitomo Pharma Co., Ltd.; and Otsuka Pharmaceutical. The authors report no other conflicts of interest in this work.

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