Mental Health Experiences and Challenges Among Individuals with Myasthenia Gravis: Insights from Patient-Centered, Qualitative Analyses

Abstract

Introduction

Historically, anxiety and depression rates have been higher among individuals with myasthenia gravis (MG) than the general population, and self-reported sentiments and experiences of mental health impairment may be more common than formal diagnoses. Patient-centered research can provide insight into self-described anxiety and depressive symptoms and stressors experienced by those with MG in the United States (US) and improve understanding of the current prevalence of anxiety and depression.

Methods

Insights were collected from three sources. First, a literature review of quantitative and/or real-world studies of anxiety/depression among individuals with gMG in the US. Second, a secondary, qualitative analysis of the transcripts from focus groups conducted with 12 individuals with self-reported generalized MG. Third, analysis of thousands of online conversations between people with self-reported ocular or generalized MG using search, data extraction, and artificial intelligence-powered algorithms. No statistical analyses were performed.

Results

The literature review identified three studies (precluding a meta-analysis): prevalence estimates for depression were 19% (diagnosed), 31% (receiving antidepressants), and 75% (self-reported sentiments), and for anxiety were 17%, 19% (both diagnosed), and 82% (self-reported sentiments). Unique stressors and triggers were identified, classified into four categories: experience of symptoms/uncontrolled symptoms; burden of medical care; daily life functioning, responsibilities, and aspirations; and social support needs. The relative prominence of each stressor and its induced emotion varied by stage in the disease journey: fear and anxiety were discussed more frequently prior to MG diagnosis, whereas hopelessness and depression became more prominent later, during ongoing disease monitoring and management. Patients felt that stress worsened symptoms in a positive feedback loop.

Conclusion

This qualitative, hypothesis-generating study found that individuals with MG in the US were more likely to report experiencing anxiety and depression than the general population due, at least in part, to their MG-specific disease journey and the uncontrolled symptoms experienced.

Supplementary Information

The online version contains supplementary material available at 10.1007/s12325-025-03399-x.

Key Summary Points

Why carry out this study?

Individuals with myasthenia gravis (MG) experience anxiety and depression at higher rates than the general population, and the mental health burden of chronic illness is reported.

This exploratory, patient-centered research aimed to assess the recent prevalence of anxiety and depression among individuals with MG in the United States, and to examine the adverse mental health experiences and disease-specific stressors described by individuals participating in a focus group as well as those discussing their experiences online.

What was learned from this study?

Individuals with self-reported MG describe experiencing unique stressors and triggers that vary by stage in the disease journey, and report that stress may further worsen MG symptoms in a positive feedback loop.

These findings elevate the patient voice and lay the groundwork for future research into depression and anxiety in people with MG.

Introduction

Myasthenia gravis (MG) is a rare, heterogeneous, antibody-mediated autoimmune condition of the neuromuscular junction, characterized by impaired neural transmission, which leads to weakness of skeletal muscle [1]. The majority of individuals with MG initially present with ocular symptoms, but ~ 30–70% will develop generalized MG (gMG), usually within 2 years [2–4], which can affect bulbar, facial, limb, axial, and respiratory muscles [5]. Muscle weakness fluctuates over time, and many individuals experience frequent fluctuations and exacerbations even when their MG is considered well controlled [6, 7]. Thus, despite several treatment options [8], many people with MG still experience substantial disease burden and impaired health-related quality of life [9–11].

Anxiety and depression occur more frequently in individuals with MG than in the general population. Prevalence among those with MG has been estimated at 33% for anxiety and 36% for depression [12]; in an international study employing the Hospital Anxiety and Depression Scale, around one-third had moderate/severe anxiety and one-fifth moderate/severe depression [13]. By comparison, global estimates of anxiety and depression in the general population in 2015 were 3.6% and 4.4%, respectively [14], and in the United States (US), 8.8% of adults had a major depressive episode over a 1-year period in 2021/2022 [15]. However, there is geographic variation in MG prevalence [16], and the incidence has increased over recent years and decades [17, 18]. Furthermore, anxiety and depression rates have increased worldwide [19, 20]. Therefore, as the only available estimates of anxiety and depression rates among patients with MG are global, covering a broad timeframe, there exists an unmet need for a recent, US-specific statistic.

The negative impact on mental health of living with a chronic medical condition is well established [21–24], and disease-specific stressors associated with mental and emotional health have been explored for many conditions [25–29] including MG [30, 31]. Deeper understanding of the disease-specific factors that drive anxiety and depression in MG can guide quantitative research and aid clinicians in holistic treatment approaches, thus improving patient care.

Therefore, this exploratory, patient-centered research was conducted with the aim of understanding the recent prevalence of anxiety/depression among those with MG in the US, as well as improving understanding of adverse mental health experiences and identifying disease-specific stressors experienced throughout the disease journey. To achieve this aim, a novel methodological approach was employed to discern patient perspectives utilizing multiple, complementary data sources. Findings will provide valuable information about the connection between MG and poor mental health and provide a platform for hypothesis generation and future research.

Methods

Research Overview and Objectives

The two research objectives were (1) to estimate the prevalence of anxiety and depression among individuals with gMG in the US, and (2) to identify, elucidate, and categorize the key stressors encountered by these individuals.

Insights were obtained from analysis of three different sources: a literature review to identify recent, published rates of anxiety/depression among patients with gMG; a secondary, qualitative analysis examining the transcript of focus groups in which patients with gMG discussed disease-related life experiences; and a qualitative analysis of public-domain, online conversations between thousands of individuals with MG. The first two focused on individuals with gMG and the third included all patients with MG (gMG and ocular MG). Only US patients were included in these analyses.

Rapid Literature Review

Objectives, Criteria, and Definitions

A literature review was conducted with the primary objective of estimating the prevalence of anxiety and depression among individuals with gMG in the US between 2014 and 2023. A secondary objective was to describe results pertaining to disease-specific stressors in the publications identified, with a particular focus on sustained symptom control in gMG.

Inclusion criteria were quantitative and/or real-world studies reporting prevalence estimates for anxiety or depression in a US population of individuals with gMG. Anxiety and depression were defined as any diagnosis of anxiety or depression (including individual items within a validated instrument) or patient-reported symptoms of anxiety or depression and related emotions.

Exclusion criteria were: study/publication types that were not quantitative and/or real world (i.e., systematic reviews/meta-analyses, case reports/case series, editorial/commentary/opinion/review article, treatment guidelines, study protocol publications, drug profiles, clinical trials, evaluations of instrument or diagnostic tests, or preclinical studies); individuals studied were < 18 years of age; individuals had a condition other than MG or MG was not the sole focus of the study; individuals had ocular MG only; evaluation of the impact of the COVID-19 pandemic (i.e., comorbid MG and COVID); not English language.

Databases and Search Terms

A literature search of PubMed and Embase databases was performed using the following search strings: {[myasthenia gravis(MeSH Terms)] AND [anxiety(MeSH Terms)] OR [depression(MeSH Terms)] OR [disorder, mood(MeSH Terms)] OR [disorders, mood(MeSH Terms)] OR [stress, psychologic(MeSH Terms)] OR [stress, psychological(MeSH Terms)] OR [stress, emotional(MeSH Terms)] OR [“mental health”(MeSH Terms)] OR [psychology(MeSH Terms)] OR [quality of life(MeSH Terms)] OR [epidemiology(MeSH Terms)]} AND {[“2014”(Date—Publication): “2023”(Date—Publication)]}.

Analysis

Publications were manually screened for relevance by an epidemiologist and real-world evidence specialist (Rachelle D. Rodriguez, study lead). When eligible publications had been identified, rates of anxiety and/or depression among individuals with gMG in the US were extracted when possible. The protocol stated that a meta-analysis was to be performed if sufficient data (i.e., at least three studies reporting anxiety and depression rates) were identified. Publications were also reviewed by a researcher to identify any content connected with control of gMG symptoms, descriptions of emotions, and descriptions of disease-specific stressors.

Exploratory Focus Group Analysis

Objectives, Criteria, and Definitions

This secondary analysis was performed on the transcript of focus group sessions that had been conducted previously with the aim of improving understanding around the experiences of those living with gMG. The objective of this analysis was to identify and categorize the mental health-related experiences and stressors described unprompted by the focus group participants.

Participants were part of the gMG Patient Engagement Research Council (PERC) convened by Janssen [32]. A PERC is a diverse group comprising disease-aware participants living with chronic health conditions who can provide their insights and feedback around a specific, semi-structured and structured series of activities.

Eligible participants were adults (aged ≥ 18 years), residing in the US, with a self-reported diagnosis of gMG. Subjective sampling was applied, in which participants were selected based on characteristics including age, gender, race/ethnicity, time since diagnosis, disease severity/treatment experiences, and age at diagnosis, to ensure diversity.

Focus Group Sessions

In February 2023, 16 individuals (13 patients and 3 caregivers) participated in multiple structured, virtual, live focus engagements conducted by a professional moderator and patient experience specialist (Wesley Peters, study author). Participants were financially compensated for their time. The analysis reported in this manuscript focused on two of these engagements, each including six participants (total n = 12) and lasting for approximately 2 h. The purpose of these sessions was to learn about the disease journey, symptoms, and diagnosis experience of participants. A discussion guide was developed by a research specialist with additional review by senior researchers and sponsor representatives. Participants were asked questions about their daily life with MG, health, and overall disease journey, with no specific guidance about mental health. Focus groups included live, active input/questions from researchers. All discussions were recorded (audio only) and transcribed.

Ethical Approval

Participants were informed that participation was voluntary, that responses would be recorded, that no treatments would be provided, and that they could withdraw at any time. Participants signed an informed consent and release form that communicated confidentiality and Health Insurance Portability and Accountability Act (1996)-compliant practices. The study did not undergo full review by an institutional review board as all data collected were anonymized. The focus groups and analysis were conducted in accordance with the Helsinki Declaration of 1964 and its later amendments.

Analysis

Focus group transcripts were qualitatively analyzed post hoc by an epidemiologist and real-world evidence specialist (Rachelle D. Rodriguez, study lead) to identify text responses made by individuals with MG that were connected in any way to mental health, emotions, and/or stressors. Thematic analysis [33] was conducted, whereby specific categories were developed during the initial review as each distinct concept was described by participants, and each text response was assigned to one or multiple categories. Transcripts were then reviewed for a second time to ensure that all relevant text responses had been captured. A new category was created if a text response did not fit into any of the previously created categories. Categories were then reviewed according to established social epidemiology concepts and scientific research, and, if required, were consolidated and a second tier of categories created. Finally, category names and groupings were reviewed and edited by the authors until a consensus was reached.

Digital Conversation Analysis

Objectives, Criteria, and Definitions

The objectives of this analysis were to describe the emotional consequences of living with MG, to identify different stages of the journey experienced by individuals with MG, to describe the relative prominence of each emotion at each of these stages, and to identify triggers for emotions, as reflected in online, public-domain conversations.

Conversations and/or online comments were limited to those conducted in English language, originating from US internet protocol addresses, over a 12-month period from August 2021 to August 2022. Data sources included message boards/forums (e.g., Reddit, Daily Strength, and Mayo Clinic), topical sites (e.g., Myasthenia Gravis Foundation of America website [https://myasthenia.org], http://www.patientslikeme.com, and the Health Union community Myasthenia-Gravis.com [https://myasthenia-gravis.com]), social networks, and blogs. Conversations were mined by the topic of “myasthenia gravis”.

Anxiety and depression were not defined a priori. All of the categories, themes, and definitions reported were “naturally occurring” within the data and identified as part of the analytical process.

Ethical Considerations

Topic-specific data were collected from public domain sources only. These data were collected in an unidentified manner, and analysis was conducted on aggregated data only. No personal information, identifiers, or other identification-related information were collected. Data were stored on secure servers only while analysis was conducted and then purged per General Data Protection Regulation privacy guidelines. The study was therefore exempt from the need for institutional review board review.

Analysis

Detailed methods have been described previously [34–36]. In brief, advanced search, data extraction, and artificial intelligence-powered algorithms were used to mine, harvest, and structure digital public-domain conversations using Human Dot Plus (Miami, FL; previously CulturIntel™) methodology.

Digital conversations were tagged and sorted, identifying the most frequent discussion topics through natural language processing and text analytics. Thematic analyses examined the most frequently discussed aspects of the journey taken by individuals with MG (in order to divide this journey into stages), their emotions, and emotional triggers. Analyses were human-assisted (Caroline R. Brethenoux and colleagues) and included repeated training, testing, and reviewing of the program output.

Each digital conversation was then assigned to one of the possible stages of the patient journey in MG (which had been identified via thematic analysis, as described above). Emotions and their most recurrent emotional triggers (also identified via thematic analysis) were then mapped to each stage of the journey.

Where possible, conversations were analyzed across all individuals with MG. Characteristics were determined by scanning conversations for self-identification based on open user profile attributes and/or contextual text descriptions provided by the unsolicited digital conversations and comments analyzed.

Results

Literature Review

Studies Identified

Initial database searches identified a total of 214 records (174 in PubMed and 40 in Embase). Following record screening for relevance and eligibility, 70 full-text publications were then reviewed in full. Of the 70 publications, 67 were rejected and three were selected for inclusion (Supplementary Material Figure S1). The main reason for rejection was that the study did not include individuals with MG from the US (n = 55).

In these three publications, the study populations, data sources, definitions of anxiety and depression, and methods of assessment varied substantially (Table 1). None included random sampling.

Table 1.

Summary of studies identified in the literature review

		Jackson et al. 2022 [36]	Mahic et al. 2022 [38]	Mahic et al. 2023 [37]
Methods	Study design	Qualitative study: semi-structured, in-depth concept elicitation interviews	Point-in-time survey: Adelphi Real World MG Disease Specific Programme	Retrospective database analysis: IBM® MarketScan® Commercial and Medicare claims
	Population	Adults with self-reported gMG in the US (N = 28)	Physicians and their patients (mean age 55 years) with ocular MG or gMG in the US (N = 456)	Adults newly diagnosed with MG in the US (N = 7,194)
	Definition of anxiety/depression	Self-reported emotions, not diagnosed and not systematically collected	Diagnosed anxiety, and depressiona	Defined using ICD codes
Results	Prevalence of depression	75%	31%	19% (prior to index, 13%)
	Prevalence of anxiety	82%	19%	17% (prior to index, 11%)
	Descriptions of other emotions	“Emotional impacts as a result of MG” reported by 100% Frustration reported by 64% Ambivalence reported by 50% Stress reported by 32%	N/A	N/A

gMG generalized myasthenia gravis, IBM International Business Machines Corporation, ICD International Classification of Diseases, MG myasthenia gravis, N/A not applicable, US United States

^aDepression prevalence based on those receiving antidepressants

Prevalence of Anxiety and/or Depression in Published Literature

Study design, study population, and estimated rates of anxiety and/or depression for the three identified studies are summarized in Table 1 [37–39]. Anxiety and depression were discussed in all three. However, only two prevalence estimates of diagnosed depression or anxiety were reported; one study instead reported participants’ descriptions of emotions [37]. There were therefore insufficient data to allow for a meta-analysis.

One available prevalence estimate for diagnosed depression in individuals with gMG was 19% (n = 7,194) [38]. One study reported that 31% of individuals with gMG were receiving antidepressants (N = 456) [39]. Diagnosed anxiety estimates were 17% and 19% (N = 7,194 and n = 456, respectively) [38, 39]. Self-reported sentiments of anxiety and depression occurred in 82% and 75%, respectively (N = 28) [37].

Stressors Described in Published Literature

All three publications reported results reflecting the fact that people with gMG can experience uncontrolled symptoms [37–39], though only one of these (a qualitative study) provided insight into the association between this and poor mental health [37]. In the qualitative study, 96% (27/28) of participants described how the presence and/or severity of symptoms often fluctuated over the course of a day or from one day to another, and 82% identified “symptom management” as a treatment goal [37]. Anxiety was described as a state of fear and worry associated with specific symptoms, lack of treatment availability, or costs [37]. gMG symptoms impacted work/career, finances, social time with family and friends, dating, physical functioning, and activities of daily living [37]. Participants expressed frustration at the impact on their quality of life [37]. Stress, anxiety, and high-pressure life events could exacerbate symptoms [37]. Some viewed their condition (or particular aspects of it) as a hurdle to deal with and accept as a part of life [37].

Exploratory Focus Group

Focus Group Participants

Twelve US-based adults, aged between 33 and 70 years (median 53 years) with a self-reported diagnosis of gMG participated in the focus groups. Six participants identified as female, five as male, and one as non-binary. Six participants were White, four Black/African American, one Hispanic/Latino, and one Native Hawaiian/Other Pacific Islander. Educational background was described as a bachelor’s degree by five participants, graduate degree by two, high school by two, “some college” by two, and technical school or equivalent by one. Participants had been diagnosed with MG between 2 and 35 years prior to participation.

Discussion of Mental Health and Emotions in the Focus Groups

Two participants stated that they had experienced depression and five directly stated that they had experienced anxiety (Table 2). In addition, two referred to feelings of hopelessness/despair, and one each described experiencing trauma, guilt, and difficulty controlling their emotions. In contrast, one individual had a positive or hopeful mindset (see Table 3 for representative quotes from the participants).

Table 2.

Concepts identified during analysis of focus group transcripts

	Concept	Participants who referred to concept, n/N (%)
Mental health/emotions	Depression	2/12 (17)
	Anxiety	5/12 (42)
	Hopelessness/despair	2/12 (17)
	Trauma	1/12 (8)
	Guilt	1/12 (8)
	Difficulty controlling their emotions	1/12 (8)
	Positive/hopeful mindset	1/12 (8)
Stressors	Experience of gMG symptoms or uncontrolled symptoms	12/12 (100)
	Burden of medical care	12/12 (100)
	Daily life functioning, responsibilities, and aspirations	12/12 (100)
	Social support needs	7/12 (58)
Negative impact of stress and/or emotions on gMG symptoms		5/12 (42)
Resilience (or lack thereof)		7/12 (58)

gMG generalized myasthenia gravis

Table 3.

Depression, anxiety, and other emotions as described by members of the generalized myasthenia gravis Patient Engagement Research Council in focus group sessions

Emotion	Representative quotes
Depression	“And so, one of the hardest things […] with myasthenia gravis is your mental [health]. I’ve gone into deep depression. I’ve been admitted into mental hospitals. It’s just… it’s crazy.”
	“I experience the same mental effects that [another participant] has […] I do take anti-anxiety medication and antidepression medication.”
Anxiety	“I’m not going to lie to you, I’m really scared. I’m really scared […] I want to keep having hope that I can live a good life and not deal with all of this emotional stuff, anxiety, extreme anxiety, panic attacks.”
Hopelessness/despair	“And I gave up. I was like, this is it. This is the way I’m going to live. Everybody thinks I’m crazy […] So I want to be grateful, but there’s so much that I could get and I’m just not getting anything […] I would live a life as if I never had myasthenia. And I know that’s a dream world, probably.”
Trauma	“[Something that] hardly anybody talks about is past traumas. Like how—why—is our immune system attacking itself? […] I wish we, as a group, would discuss that mental part of it.”
Guilt	“That’s how I feel. I feel guilty. I feel like I’m not pitching into society the way I want to.”
Positive/hopeful mindset	“Just having a goal. Even if it’s unattainable, it gives you purpose and it gives you something else to focus on than on the pain […] I’m allowed to dream and have goals […] And that is helping my mental [health], the depression and the anxiety […] I feel hopeful because […] 30 years ago, there wasn’t this.”
Difficulty controlling emotions	“I tried to be managing control of my emotions.”

Stressors Described in the Focus Groups

Stressors were identified and categorized according to established social epidemiologic concepts. Categories and sub-categories are outlined in Table 4, along with representative participant quotes. Most commonly, the stressors described had an adverse impact on mental health, although some—such as positive relationships with healthcare practitioners (HCPs) or a supportive family—had a positive impact.

Table 4.

Stressors described by members of the generalized myasthenia gravis Patient Engagement Research Council in focus group sessions

Stressor category	Subcategory	Representative quote
Experience of symptoms or uncontrolled symptoms		“Everything became completely unstable for me, and I just kind of felt like I wasn’t going to make into the next year.”
Burden of medical care	Patient–HCP interactions and care burden	“I changed my neurologist a couple of times because I felt they weren’t giving me the proper care […] It is frustrating when they don’t—the medical field, especially at the hospital—don’t know fully what myasthenia gravis is.”
	Insurance-related treatment access	“He says ‘I can now treat you because you have different insurance.’ I was so upset because I went three years untreated because insurance wouldn’t allow him to even try.”
	Treatment burden	“I’m just having the hardest time […] I’m so sick of so many medications […] Because going to the hospitals, it’s so draining.”
Daily life functioning, responsibilities, and aspirations	Employment responsibilities and career	“So that’s been the struggle we’re in now. I had to stop working for a number of months at a time, several times.”
	Familial responsibilities and interpersonal relationships	“I tried to take my kids out and do some stuff yesterday and the stress of having things go on and just trying to keep up with them—my daughters are like nine now. I just can’t do it […] It’s very physically taxing. It’s emotionally taxing.”
	Personal care and activities	“And it’s very upsetting to me to not even be able to get out of the house […] I get like maybe a week that I actually can get some stuff done. And that’s like clean the house up after stuff I haven’t done.”
Social support needs	Emotional support	“I’m more fortunate than others because I’m in a self-help and support group.”
	Instrumental support	“My younger son said, ‘Dad, you need to move in with me so I can watch you’ […] I just fear that I can’t push myself and not have someone there, actively there with me to watch and see what’s going on.”
	Informational support	“[My doctor] knows I live by myself, and he will ask me about the medication if I’m having any side effects or anything like that. And he’s one that I can actually get on the phone and call if I’m having any problems.”

HCP healthcare practitioner

All participants described stressors associated with the “experience of gMG symptoms” or “uncontrolled symptoms”, and often considered that these negatively impacted their mental health (Table 2). Symptoms described included difficulty swallowing, walking issues, weakness, and brain fog. Participants also often referred to symptom fluctuation/unpredictability, using terminology such as “makes the myasthenia worse,” “flare-ups,” “unstable,” or “triggering.” The frustration brought about was summarized by one individual as: “I just want to be able to do things that brought me great joy and I could do those again if my symptoms were better.”

All participants described stressors associated with the “burden of medical care” (Table 2). The subcategory “patient–HCP interactions and care burden” refers to participants discussing the challenge of identifying (and obtaining care from) a suitable neurologist with appropriate experience and knowledge of gMG, their feelings about suboptimal care, and having to travel long distances. In contrast, some described positive relationships with HCPs in which they felt heard, suggesting that HCPs can be an important source of support and may counter the impact of stressors.

In the subcategory “insurance-related treatment access,” participants described the negative impact of insurance coverage not permitting particular treatment options as well as high out-of-pocket expenses. In the subcategory “treatment burden,” participants described being “sick of so many medications,” the draining effect of attending medical appointments, and concern around regular admittance to the intensive care unit due to exacerbations.

All participants described stressors associated with “daily life functioning, responsibilities, and aspirations” (Table 2), highlighting the impact that unstable MG symptoms can have on patients’ lives. The subcategory “employment responsibilities and career” refers to participants’ inability to meet expectations at work or to able to work at all, either due to symptoms or to time spent in hospital. The subcategory “familial responsibilities and interpersonal relationships” refers to marital strain due to misdiagnosis (before the correct diagnosis of MG) or the physical and emotional toll of participating in family life with children/grandchildren.

In the subcategory “personal care and activities,” participants emphasized their fears and/or distress about being unable to swallow, to walk very far, to leave their home, or to clean. Some described having to be mindful not to “overdo it,” as this would further impede their ability to partake in activities; one participant mentions that this could render them “flat on my back for 2 days, if I’m not careful.”

Seven participants described stressors associated with “social support needs” (Table 2) due to the burden of symptoms and the loneliness that may result. For example, one individual described the way in which unpredictable symptoms make it difficult to make and adhere to social or work plans, and how a lack of understanding by others has a negative impact: “I can’t make plans and I have to explain it to a lot of people, which they are not happy with […] I’ve lost a lot of friends. I’ve isolated myself a lot.”

Three social support categories were identified. “Emotional support” refers to participants benefiting from support groups, including one who described feeling fortunate to be part of a self-help/support group, and another who acknowledged a social media-based support group. “Instrumental support” refers to assistance provided to meet tangible needs, either due to its presence (e.g., reminders from housemates or family members to rest or eat) or absence (e.g., the particular importance of not “overdoing it” for an individual who lives alone). Finally, “informational support” refers to participants describing a good relationship with their physician, as they value being able to contact them when problems arise.

Impact of Stress on gMG Symptoms Discussed in the Focus Groups

Five participants discussed the negative impact of stress and/or emotions on their gMG symptoms (Table 2). Representative quotes are shown in Table 5. Participants referred to their attempts to manage and minimize stress levels as they found that increased stress triggered MG symptoms, including impairment of vision, speech, and ability to swallow. A clear correlation was described, with participants making comments such as “if I get stressed out, I’m definitely going to get worse”, or “everybody in here knows that stress can be just as triggering to symptoms as anything else.”

Table 5.

Negative impact of stress/emotions on myasthenia gravis symptoms as described by members of the generalized myasthenia gravis Patient Engagement Research Council in focus group sessions

Impact	Representative quotes
Negative impact	“To me, stress makes the myasthenia worse. If I get stressed out, I’m definitely going to get worse. I try to not get stressed.”
	“I progressed greatly for about 20 years with little flare-ups here and there depending on my stress level.”
	“If I get highly stressed, it’ll affect my vision […] Stress affects my speech and my ability to swallow.”
	“Everybody in here knows that stress can be just as triggering to symptoms as anything else.”
	“Stress is always a trigger for me.”

Evidence of Resilience Among Participants in the Focus Groups

More than half of the participants (n = 7) referred to resilience (Table 2). Resilience can be defined as the process of effectively negotiating or managing significant sources of stress or trauma [40], and resilience in an individual can be influenced by biological, psychological, and social factors [41]. In this study, resilience was described in positive or negative terms (i.e., hope versus despair). One individual described it thus: “I’m allowed to dream and have goals. And that is helping my mental health, the depression and the anxiety.” In contrast, another reported “giving up” at times and feeling resigned to their life with gMG.

Digital Conversation Analysis

Online Conversations

In total, 9901 unique digital conversations about MG were extracted. Of these conversations, 38% took place on message boards, 33% on topical sites, 17% on social networks, and 12% on blogs.

Discussion of Mental Health and Emotions in Online Conversations

Emotions discussed online by individuals with MG were depression, anxiety, fear, and hopelessness (see Table 6 for definitions). As one individual stated: “I’m so depressed! This is horrible; I can hardly function.”

Table 6.

Emotions discussed online by individuals with myasthenia gravis and the triggers for each of these emotions

Emotion	Definition of emotiona	Trigger	Description of trigger
Depression	Having persistent feelings of sadness and despair, specifically related to the challenges posed by MG	Progressive worsening	The deterioration of physical health or worsening symptoms
		Impact on quality of life	How the condition impacts daily life, activities, or overall well-being
		Ineffective treatment	Lack of efficacy with no improvement of symptoms
		Lack of control	Feeling out of control or unable to influence outcomes
Anxiety	Increased worry and unease stemming from unpredictable symptoms of MG, potential exacerbations, and impact on daily life	Symptomatic discomfort	Distress, inconvenience, or pain caused by the actual symptoms of the condition
		Uncertainty	Not knowing what’s coming next, or how the condition will progress
		Fatigue	Constant tiredness or lack of energy
Fear	A heightened emotional response to the uncertainties and challenges of MG, often tied to concerns about symptoms, functioning, and impact on daily life	Catastrophizing thoughts	These represent negative and often exaggerated thoughts about one’s situation
		Physical impact	The concrete effects of the condition on the body’s state, including symptoms, discomfort, and fatigue
		Financial impact	The economic strain of the condition, either due to treatment costs or inability to work
		Relationship impact	How the condition affects relationships with loved ones, friends, or colleagues
Hopelessness	A feeling of despair and discouragement brought about by the chronic nature of MG, leading to doubts about future improvements in symptoms and quality of life	Dire prognosis	Pessimistic outcomes or beliefs about the condition
		Burden on others	Feeling like one’s illness is causing strain or stress on loved ones
		Unfulfilled dreams	Emotional pain of not being able to achieve life goals due to MG
		Lack of options	A feeling that there aren’t enough treatment choices available
		Loss	Loss of life like it used to be, including physical/social/professional life

MG myasthenia gravis

^aDefinitions were not defined a priori, but were generated during the thematic analytical process

The patient journey, as indicated in online conversations

The journey taken by individuals with MG comprised four different stages:

• suspicion of MG prior to diagnosis (individuals express concern due to manifestations of symptoms).

• diagnosis (individuals have been diagnosed with MG and are coming to grips with the reality of their condition).

• initial management of MG (people feel that they are enduring the process).

• ongoing disease monitoring and management (individuals are undergoing treatment, assessment, and reevaluation of their treatment plan).

Of the total number of conversations (N = 9,901), 21% occurred during the suspicion stage, 33% around diagnosis, 35% when they were initially managing their condition, and 11% during ongoing management (percentages did not total 100% due to rounding).

Emotional Triggers Discussed in Online Conversations

Each emotion had unique triggers, as described in Table 6. Depression was triggered by worsening symptoms, reduced quality of life, ineffective treatment, and a feeling of lack of control. Anxiety was triggered by discomfort due to MG symptoms (defined as distress, inconvenience, or pain caused by the actual symptoms of a condition), a sense of uncertainty, and fatigue. Fear was triggered by catastrophizing thoughts, physical impact, and the impact of living with MG on the individuals’ finances and relationships. Finally, hopelessness was triggered by pessimistic beliefs about MG, burden on others, being unable to achieve life goals, lack of treatment options, and a sense of loss.

As exemplified by the following quotes, reduced quality of life and ineffective treatment can trigger depression: “I long for my life as it used to be” and “I’m utterly depressed. Not a single doctor can figure this out.” Symptomatic discomfort can trigger anxiety: “Ever since my MG symptoms got so bad, my anxiety has been through the roof.” Physical symptoms can trigger fear: “My legs get heavy, and suddenly I can’t walk. My balance is off, and I start tripping over my own feet. I’m so scared; things are getting worse.” The feeling of being a burden on others due to symptom worsening can trigger hopelessness: “I’m getting worse; there is nothing I can do to not be a burden on my family.”

Emotional Triggers Throughout the Patient Journey

The relative dominance of each emotion changed throughout the patient journey (Fig. 1). The most prominent emotion prior to MG diagnosis was anxiety, and at diagnosis was fear. Depression then increased in frequency and dominated through the later management stages. No conversations about hopelessness were reported in the earlier stages; this became more prominent during ongoing management.

Fig. 1.

Changes in the relative prominence of each emotion experienced at different stages of the journey from suspicion of myasthenia gravis through diagnosis and treatment to long-term assessment, as discussed online by individuals with myasthenia gravis

Discussion

Understanding the factors and experiences that can impact mental health in individuals with MG can inform optimal patient care. In this exploratory, patient-facing research, insights were collected from a literature review and from qualitative analysis of both focus group transcripts and thousands of online conversations between people with MG.

The first objective was to estimate the prevalence of anxiety and depression among individuals with gMG in the US via a literature review of quantitative and/or real-world studies. Up-to-date estimates are needed because the rates of both MG and anxiety/depression have been increasing in the US. The literature review identified three studies, precluding a meta-analysis and highlighting an unmet need for comprehensive research into depressive symptoms and anxiety in patients with MG. Two studies reported anxiety/depression rates among those with MG [38, 39]; these rates were nearly double those observed in matched controls [38] or in the general US population [15]. Importantly, however, self-reported sentiments or experiences of anxiety and depression may be substantially higher than formal diagnoses, based on the findings of a prior qualitative study [37] and our qualitative analyses. These experiences likely vary temporally, with anxiety being more prominent at the start of the patient journey, and depression becoming increasingly common at later stages.

The second objective was to identify, elucidate, and categorize the key stressors encountered by individuals with MG in the US. During deeper investigation into the types of stressors and triggers of anxiety and depression mentioned in the self-reported experiences, repeating themes were noted. Overlap between the findings of the three analyses is illustrated in Fig. 2. Stressors included themes similar to those experienced by people with other chronic and rare diseases, in addition to some aspects unique to MG. Many of the sentiments captured are consistent with those observed in other studies into the lived experience of MG in Europe, the US, and New Zealand, which used a variety of methodological approaches [10, 30, 42, 43]. In our study, however, a proposed organizational structure was developed, consisting of four key categories: (1) experience of symptoms or uncontrolled symptoms, (2) burden of medical care, (3) daily life functioning, responsibilities and aspirations, and (4) social support needs.

Fig. 2.

Insights into the experiences affecting mental health among individuals with myasthenia gravis in the United States, as indicated by research centered on patient data. Concepts were initially determined via qualitative analysis of discussions that took place during patient focus groups; key stressors were identified and categorized, and additional insights connected with resilience and the triggering of generalized myasthenia gravis symptoms by stress and related emotions were determined. Results of a digital conversation analysis and literature review were then evaluated for alignment with these concepts. *The digital conversation analysis methodology was not designed to investigate this aspect of the patient experience

Many stressors were connected with the occurrence of uncontrolled MG symptoms. Focus group participants referred to symptom fluctuation and unpredictability, expressing a wish to obtain control, and online conversations revealed that factors such as symptom discomfort, symptom worsening, and ineffective treatment were triggers of depression, anxiety, fear, or hopelessness. In a prior qualitative study, anxiety has been described as a state of fear and worry associated with specific MG symptoms [37].

Stressors were also connected with the burden of medical care. Focus group participants described the challenges and frustrations associated with obtaining the most appropriate care from their physician, as well as insurance-coverage-related barriers. Online conversations showed that depression or hopelessness can be triggered by the feeling that one is not receiving effective treatment, or a lack of apparent treatment options. This category highlights some of the challenges associated with current standards of care and prescribing practices.

Similar relationships between symptom and/or treatment burden and mental health and well-being have been previously identified in people with other chronic conditions, such as immune thrombocytopenic purpura [27] or chronic obstructive pulmonary disease (COPD) [28]. The particular importance of unpredictable symptom fluctuation (which can impair one’s ability to predict or control upcoming situations, a feature that characterizes the development of anxiety [44]) has also been observed in other conditions: for example, among individuals with COPD, unpredictability of disease course (and hence difficulty planning for the future) was identified as a source of strong emotional distress, triggering feelings of anxiety, sadness and uncertainty [45], and among people with diabetes, an association between diabetic neuropathy and anxiety/depression is mediated by patient perception of symptom unpredictability [46].

A third category of stressors was connected with daily life functioning, responsibilities, and aspirations. Focus group participants described concerns around their impaired ability to work, the physical and emotional toll of participating in family life, and a reduced ability to accomplish personal care and activities. Online conversations referred to the triggering of fear, depression, or hopelessness by factors ranging from the financial and relationship impacts of the disease to a sense of loss and unfulfilled dreams. This concurs with previous qualitative studies in which MG symptoms impacted work, career, finances, social time with family and friends, and dating [30, 37, 42]. Limitations connected with the activities of daily living and the associated loss of independence have previously been identified as an independent risk factor for depression, particularly among older adults [47, 48]. This category highlights the wide-ranging impact that uncontrolled and unpredictable symptom fluctuation can have on a patient’s life, indicating an unmet need for treatment options that provide durable, consistent control.

Finally, many stressors were connected with social support needs. Focus group discussions highlighted the impact of the presence or absence of emotional, instrumental, or informational support provided by self-help and support groups, family and friends, or HCPs. Online conversations referred to uncertainty, catastrophizing thoughts, quality of life, and a sense of loss or unfulfilled dreams (all of which reflect a need for additional support) triggering depression, anxiety, fear, or hopelessness. Studies across a variety of clinical areas (including breast cancer, nurses working during the COVID-19 pandemic, and people with rare diseases) corroborate the role of such support as a buffer to the negative consequences of stressful experiences [26, 49–52], and our results indicate that this may also be relevant among individuals with MG experiencing poor symptom control.

Taken together, the findings described here demonstrate that key stressors experienced by individuals with MG can be identified, elucidated, and summarized into categories. We provide a proposed organizational structure and an in-depth understanding of MG-related stressors. Addressing these stressors could have a positive effect on outcomes for individuals living with MG, improving their mental health and quality of life.

To address stressors connected with uncontrolled symptoms and the burden of medical care, individuals with MG should be under the care of neuromuscular specialists [53, 54] and, if possible, experts in MG diagnosis and treatment. The broader care team should be multidisciplinary and include physical/occupational/speech therapists, social workers (who can assist with prompt access to available resources), mental health specialists [55, 56], and primary care physicians, as required. The optimal MG care pathway is patient-centered [57] and includes interventions and processes related to the following: speech, swallowing, and dental treatment; occupational, physical, and respiratory activity; psychological functioning; lifestyle activities (such as nutritional changes, safe exercise programs, infection control, avoiding heat, and staying well hydrated); myasthenic crisis management; and pharmacologic interventions [58]. In addition, there is a need for immune-specific treatment strategies that achieve rapid, durable stabilization of MG symptoms.

Results also highlight the importance of evaluating the psychological impact of living with a rare disease, and of ensuring that patients receive the most appropriate support. Neurologists should consider routinely screening their patients for anxiety and depression.

Effective, open communication between HCPs, patients, and caregivers is crucial to address many of the stressors and to help alleviate the sense of disconnect that has been previously reported by some patients with MG [30]. The experience of living with MG and feelings of lack of control should be acknowledged and validated. The care team can empower patients by directing them to online resources developed specifically for patients, including guidance around discussing MG with family/friends and employers [59, 60] and overcoming financial barriers to treatment [61, 62]. Patients often find that involvement in peer support groups is beneficial [63]. Many of these are virtual, reducing geographical barriers to access; in some, individuals are paired with another patient who can help guide them through their MG disease journey [64] In addition, patients can self-advocate for improved disease control by tracking symptoms, triggers, and impacts using a journal or computer/cellphone app and discussing this with their HCP [65].

In this study, analysis of digital conversations revealed that the relative prevalence of anxiety, depression, fear, and hopelessness—and therefore of the triggers for each of these emotions—was different depending on what stage of the patient journey the individual was in at the time of the study. Thus, knowledge of risk factors and MG symptom recognition among generalist HCPs may reduce the time to diagnosis and thus reduce triggering fear and anxiety. In contrast, measures to alleviate depression may be important later in the patient journey.

Resilience appeared to affect mental health and well-being in this population. Resilience can be defined as the process of effectively negotiating or managing significant sources of stress or trauma [40] and depends on multiple biological, psychological, and social factors [41]. Some focus group participants referred to a positive or hopeful mindset, which may help to mitigate the impact of stressors, whereas others spoke in negative terms, expressing a sense of despair. Online conversations also highlighted that fear and hopelessness can be triggered by catastrophizing thoughts, pessimistic beliefs about MG, a loss of life “as it used to be,” and unfulfilled ambitions. As studies have shown that those with a chronic disease and high resilience scores have less anxiety/depression and better quality of life [66], there may be a role for interventions that increase resilience, such as psychosocial therapy and lifestyle change support [41, 67, 68]. This finding also relates back to stressors in the “social support needs” category.

Importantly, some individuals with MG described how stress led to further exacerbation of their MG symptoms in a positive feedback loop, as was also noted in a previous qualitative study [37]. Given the existing literature around stressors, exacerbations, and mental health in other chronic conditions, and the biochemical consequences of stress and adverse mental health experiences, we propose this as a potential pathway for this feedback loop among patients with uncontrolled MG (Fig. 3).

Fig. 3.

Proposed positive feedback loop of chronic stress, mental health burden, and uncontrolled symptoms among individuals with myasthenia gravis in the United States

To summarize, when an individual experiences a stressor, this contributes not only directly to their adverse mental health but also to a high allostatic load (i.e., the cumulative, negative, physiologic response to chronic stress) via activation of the hypothalamic–pituitary–adrenal axis, which further exacerbates disease symptoms [69–72]. Thus, a high allostatic load is often associated with poorer health outcomes [73] and is an independent risk factor for anxiety and depression [70, 71]. We propose that this process likely occurs in MG, though further research is needed into the biologic processes involved in allostatic load in people with MG.

Future research may also include large-scale studies of anxiety/depression prevalence; studies that delineate patients with bulbar- versus limb-predominant symptoms; longitudinal studies that track anxiety/depression over time and examine correlation with disease activity measured using validated tools; longitudinal analysis of online conversations to evaluate changes in the emotional impact of MG as new treatments and tools become available; and quantitative studies that employ random sampling and have greater scope to further elucidate the causality pathway for the increased mental health burden in MG.

This analysis has several key strengths. The methodologies used were carefully selected. Qualitative methods are considered an important component of chronic disease research and mental health research but have historically been underutilized and undervalued [74, 75]. The analysis of a focus group transcript facilitated the identification and discussion of MG-specific stressors at a fine level of detail, along with the generation of a proposed categorization structure. In addition, as those with a medical condition often turn to the internet to discuss their experiences with others, the use of advanced search, data extraction, and artificial intelligence-powered algorithms to mine these data facilitated unique and complementary insights. Such ‘social listening’ studies can discern priorities and outcomes that are important to patients without placing a burden of requirements on them, whilst also avoiding biases associated with interview design and interventional studies [76, 77]. Such an approach has revealed valuable findings across a range of disease areas, such as the existence of racial/ethnic variation in sentiments expressed in conversations about depression [36, 78], the nature of the humanistic burden of acute myeloid leukemia and myelodysplastic syndrome [79], and the relative importance of different barriers to care access for people with Alzheimer’s Disease [80], among others. Therefore, combining these two methodologies while also drawing on the insights provided in published literature elevates the patient voice. The utilization of additional sources to corroborate the findings of social listening research is considered best practice [76, 81].

The analysis also has some limitations, which may limit comparison with other research and generalizability to the wider US population of patients with MG.

The literature review did not include an exhaustive selection of databases/literature sources and involved only one researcher (in line with the definition of a rapid literature review). The number of publications identified by the literature search was low, which precluded a meta-analysis and also limited the conclusions that could be drawn regarding stressors.

In the focus group, the number of participants was relatively low (n = 12), though typical for a qualitative study of a rare disease. As participants were from the Janssen PERC, they may have been more engaged and disease-aware than randomly selected patients with MG (self-selection bias), such that the information gathered from this analysis may not be generalizable to the entire population of individuals with MG in the US.

Limitations of the use of digital conversations as a data source have been previously acknowledged [76, 77, 81]. They include self-selection bias, negativity bias, self-reporting of MG, user activity imbalance, and unique challenges associated with the analysis of text written by non-experts using colloquial language [76, 77]. Privacy and ethical considerations are also important [81]; our study took the recommended approach of extracting data from publicly available sources only and protecting privacy via anonymization [77].

As with all qualitative studies, observation bias could have influenced the results. As with all cross-sectional studies, there is temporal ambiguity in terms of the occurrence of MG and mental health conditions. As MG diagnoses were not clinically confirmed and the definition of MG/gMG varied between each analysis, misclassification was possible for the focus group and digital conversation analyses. Anxiety/depression was also not clinically confirmed, and the definition was intentionally broad to enable all relevant aspects of mental health-related patient experiences to be captured.

Associations were not tested statistically and sensitivity analyses of focus group and online conversation data were not performed. These limitations may inform and direct future research in this area.

Finally, as the decision to pursue publication was made after analyses were performed, the results are hypothesis-generating rather than hypothesis-confirming.

Despite these limitations, we believe—based on the scientific literature in other areas of chronic and/or rare disease—that the stressors and triggers reported by individuals with MG in this study have an impact on the disease course.

In conclusion, individuals with MG in the US report experiencing anxiety and depression at rates higher than are found in the general population due, at least in part, to their MG-specific disease journey and the uncontrolled symptoms experienced. A unique set of stressors and triggers for these adverse mental health consequences is experienced by individuals with MG (varying by stage in the disease journey), and a positive feedback loop may further worsen MG symptoms. These findings may inform clinicians in their approach to the treatment of individuals with MG, resulting in positive changes in patient care, and providing a platform for future research.

Supplementary Information

Below is the link to the electronic supplementary material.

Author Contributions

Conceptualization: Rachelle D. Rodriguez. Data interpretation: Rachelle D. Rodriguez, Ashley E. L. Anderson, Kelly G. Gwathmey, Lisa M. Shea, Raghav Govindarajan, Nizar Souayah, Louis A. Jackson, Zia U. Choudhry. Formal analysis and data acquisition: Rachelle D. Rodriguez, Caroline R. Brethenoux, Wesley D. Peters, Louis A. Jackson, Zia U. Choudhry. All authors reviewed and edited the manuscript and have read and agreed to the final version.

Funding

Sponsorship for this study as well as all the Rapid Service and Open Access Fees were funded by Johnson & Johnson.

Data Availability

The data that support the findings of this study are available from Human Dot Plus, but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are, however, available from the authors upon reasonable request and with the permission of Human Dot Plus (please contact Zia U. Choudhry: ZChaudhr@its.jnj.com).

Declarations

Conflict of Interest

Rachelle D. Rodriguez was an employee of Johnson & Johnson at the time of the study, and is currently consulting for Gilead Sciences through Biopoint and Star Epidemiology. Ashley E. L. Anderson has served on the speaker’s bureau for Alexion Pharmaceuticals and has served on advisory boards and as a paid consultant for Johnson & Johnson. Kelly G. Gwathmey reports consulting for Argenx, UCB, and Alexion, and speaking engagements for Alexion. Caroline R. Brethenoux is an employee of Human Dot Plus, a research company paid by Johnson & Johnson to undertake the analyses for this study. Lisa M. Shea is an employee of Johnson & Johnson, and owns stock or stock options in Johnson & Johnson. Raghav Govindarajan has served on advisory boards for Argenx, UCB, Janssen, Roche, and speakers’ bureaus for Argenx, Alexion, and UCB. Nizar Souayah reports having no conflicts to disclose. Wesley D. Peters is an employee of Evidera, which derives profits from interactions with pharmaceutical sponsors. Louis A. Jackson is an employee of Johnson & Johnson and owns stock or stock options in Johnson & Johnson. Zia U. Choudhry is an employee of Johnson & Johnson, and owns stock or stock options in Johnson & Johnson.

Ethical Approval

A post hoc/secondary qualitative analysis from transcripts of participants in focus groups were used for this study. Participants in the focus group were informed that participation was voluntary, that responses would be recorded, that no treatments would be provided, and that they could withdraw at any time. Participants signed a consent and release form that communicated confidentiality and Health Insurance Portability and Accountability Act (1996)-compliant practices. Data were anonymized. The original research was classified as market research, and therefore institutional review board approval was not needed. The focus group and analysis were conducted in accordance with the Helsinki Declaration of 1964 and its later amendments.

For the digital conversation analysis, topic-specific data were collected from public domain sources only. These data were collected in an unidentified manner, and analysis was conducted on aggregated data only. No personal information, identifiers, or other identification-related information were collected. Data were stored on secure servers only while analysis was conducted and then purged per General Data Protection Regulation privacy guidelines. The study was therefore exempt from the need for institutional review board review.