Our study demonstrates that the prevalence of depression, anxiety disorder and PTSD in MG patients is not only high among MG patients, but also underdiagnosed. Of all MG patients, 81.4% reported no diagnosed mental health condition. Patients with higher self-reported MG severity reported depression and anxiety disorder more frequently than patients with lower MG severity. Self-reported MG disease severity is strongly associated with patients HRQoL as well as caregiver burden. Beyond MG severity, depression has negative effects on HRQoL in MG patients as well as on caregivers’ burden. In addition to the effect of depression, patients HRQoL as well as caregiver burden were negatively associated by female gender of the patient and positively associated by thymectomy.
The prevalence of depression differed between 14 and 58% ,(9,20), whereas the prevalence of anxiety disorders ranged between 20 and 55% (21–23),. This variability can be explained by the considerable heterogeneity of the cohorts, sample sizes, clinical measures and assessment methods, including the diagnostic criteria used. PTSD has been reported in 51% of MG patients after an episode with respiratory insufficiency. A positive finding in PTSD screening was more likely in patients with higher HADS score values (24). The prevalence of psychiatric comorbidities in the general population in Germany (25) is much lower when compared with our findings in the MG cohort data (15.4% vs. 35.5% for anxiety disorder; 8.2% vs. 30.8% for depression, and 2.3% vs. 4.9% for PTSD). Interestingly, the PTSD screening revealed similar rates of PTSD in MG patients with a history of an exacerbation and a myasthenic crisis. Compared to the prevalence of anxiety disorder of 24 to 29% in post-stroke and 22% in multiple sclerosis patients, MG patients were substantially more often affected (26–28).
Our data based on the HADS and PTSD-7 questionnaire suggests a significant underdiagnosis of depression, anxiety disorder and PTSD in MG patients. MG patients with characteristics of depression, anxiety disorder or PTSD had a corresponding diagnosis in only 23.3%, 12.7% and 19.6%, respectively.
In the largest study to date, conducted before 2010, 38.6% of 1518 patients had diagnosed depression (10), which is three times higher than in our study but close to the prevalence established by HADS. While the other characteristics of the MG patients were very similar to our study and both were conducted in Germany, the difference is likely due to a changed situation in the care of MG patients (previously combined specialty for neurology and psychiatry with now often separated residency tracks). Our study highlights the importance of increasing the awareness of mental health conditions and the necessity of implementing diagnostic measures, such as easy to use screening tools. These tools might help to diagnose and treat comorbid mental health conditions in MG patients. For example, studies have shown, that stroke patients benefit from screening for depression (29).
The simultaneous presence of MG and depression, for example, can be challenging for diagnosing depression in MG patients and the other way around. Thus, depressive symptoms can be misinterpreted as myasthenic symptoms such as fatigue. In contrast, the difficulty in clearly distinguishing symptoms of depression from fatigability and fatigue symptoms of MG might lead to delayed or misdiagnosis in MG patients (30). It has been reported that only one patient out of ten with myasthenic symptoms is getting an adequate MG diagnosis (31). Young women are more likely to get a psychiatric diagnosis, whereas men are more often misdiagnosed with other somatic diseases (32). This is consistent with the finding of our study that women have significantly higher latencies in diagnosis than men (3.0 vs. 1.3 years). This raises the question not only of why women are diagnosed later, but also whether a higher latency of diagnosis increases the risk for depression in women. Obviously, the overlap of myasthenic and depressive symptoms in MG patients (with or without comorbid depression) leads to difficulties for physicians in making an adequate diagnosis. We demonstrated a strong association between self-reported disease severity and HRQoL, which is largely affected by comorbid depression. This is consistent with the results of a previous study of eighty patients (33). Our results suggest that depression is – amongst the variables we investigated – the most influential factor affecting the perceived MG severity and HRQoL. We cannot rule out that the effect is at least partially inverse, with higher MG severity and lower HRQoL leading to a higher likelihood to develop depression. Female gender is strongly associated with a lower HRQoL corroborating findings of previous studies (5,34). It has also been reported that female gender as well as depression are directly associated with a worse disease severity (35,36). Several factors might explain the gender differences in HRQoL including differences in experiencing and reporting the severity of symptoms in general. Female patients tend to report significantly more physical symptoms and higher symptom severity levels than men (37), which might reduce the HRQoL as shown by our results. Secondly, according to our data, female patients experience a longer latency between onset of symptoms and diagnosis. During this period, circumstances like physician hopping, inadequate therapies, experience of discrimination and humiliation and misdiagnosis due to broad differential diagnosis might be stressful and, thus, affect the HRQoL. The knowledge on the interaction of depression, gender, perceived disease severity, and HRQoL in MG patients is scarce. A recent study with 179 patients showed a moderate correlation between disease severity and depression as well as female gender (35). For other chronic diseases like chronic renal disease, rheumatoid arthritis, and cardiovascular disease depression is a known factor affecting perceived disease severity (38–40).
We observed an improved HRQoL after thymectomy. Consistent with our results, gender differences in HRQoL were abolished in MG patients after thymectomy (34). The burden of disease was lower after thymectomy, and patients had fewer exacerbations and also required less immunosuppressive medication (41,42).
Self-reported disease severity of MG and the caregiver burden are strongly associated. Depression increases the effect of this association, but it also has a direct and negative effect on the caregiver burden. In the normal population, the mental status of a care recipient is associated with the caregiver burden and, more importantly, the caregiver burden was nearly significant in predicting depressive symptoms in caregivers (43). Thus, another important aspect of MG care is the provision of supportive measures not only for patients but also for their caregivers. For example, when caregivers are under greater strain, outpatient care services and psychological assist, especially with systemic therapy, psychoeducation, and self-help groups, can provide relief in the social tension field of families. Female gender of the MG patients is associated with a lower caregiver burden, whereas female caregivers of male MG patients experience a higher burden. In general, female caregivers experience more significant caregiver burden than men (44). The higher strain has been explained by women experiencing more secondary stressors, such as financial and relational problems. Depending on the cultural background and the social norms of gender, women feel more obligated to provide care than men and feel more strain (45).
Our study has several limitations. Although our analyses are based on a large group of patients, we cannot be confident that our cohort is representative. Most participants patients were members of the national self-help group representing approximately a quarter of all German MG patients. Moreover, we investigated only German MG patients. Although the Global Burden of Disease data from the World Health Organization (WHO) shows comparable prevalence amongst high-income countries like European Countries or the United States (46), our data might not reflect the situation of MG patients in low high-income countries. Importantly, because of the cross-sectional design of our study, we cannot draw conclusions about causality.
Although the HADS is a reliable tool for assessing depression and anxiety, it is not identical to the ICD-10 diagnostic criteria. Prevalence of depression as assessed by HADS might be higher than diagnosed according to ICD-10 criteria (47). For assessing gender-related differences in QoL and disease burden we used a heteronormative approach, which does not consider non-binary gender as well as same-sex partnership. Finally, we used the MG-QoL15 scale and not yet the new slightly revised version (MG-QoL15r), which is preferred because of a slightly better performance (48).