Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease characterized by the loss of upper motor neurons in the motor cortex and the loss of lower motor neurons in the brainstem and spinal cord.1 The loss of motor neurons in these areas results in a combination of progressive extremity weakness, muscle atrophy, spasticity, dysarthria, dysphagia, and respiratory failure. The average survival for a patient diagnosed with ALS is 2 to 5 years. In addition to motor weakness, up to 50% of patients will develop some degree of cognitive and behavioral changes, with an estimated 10% to 15% resulting in frontotemporal dementia.2 Unfortunately, there is no cure for ALS, and the current standard of care for ALS is to maximize function and quality of life through multidisciplinary care. ALS care teams include varying combinations of physicians, physical therapists, occupational therapists, speech language pathologists, dieticians, respiratory therapists, nurses, psychologists, social workers, genetic counselors, and nurses. Patients with ALS will invariably be confronted with important medical decisions that may affect their quality of care or survival, such as gastrostomy placement, use of noninvasive ventilation, or use of invasive ventilation through a tracheostomy.
ALS is a life-changing diagnosis that has the potential to be psychologically devastating with unique mental health challenges. The presence of mental illness in ALS patients can be an important predictor for overall quality of life and disease outcomes. This article reviews the literature as it pertains to psychiatric disease in ALS, including diagnosis and management of mental illness.
We performed a comprehensive review of the literature. An Ovid search for the terms “ALS and mental health” returned 82 results. The key findings of selected articles are summarized in this review.
What Is Known About Mental Health in Amyotrophic Lateral Sclerosis
Multiple studies have assessed depression in patients with ALS, with a reported prevalence ranging anywhere between 0% and 40%.3 Studies that used a structured Diagnostic and Statistical Manual of Mental Disorders, fourth edition4 interview consistently found rates of depression at approximately 10%.3 In an observational study, the severity of depression correlated with disease severity at the initial assessment, but did not worsen with disease progression. Higher depression scores were associated with higher mortality and lower quality of life.5 Interestingly, a review of 28 studies over a 20-year period revealed that depression might not be as prevalent or as severe as might be expected given the nature of the disease. In fact, the prevalence of depression in ALS may not be significantly different than the general population.6
This variability in the prevalence of depression may be due to multiple factors including the specific criteria and screening methods used in the study, the severity of the depressive symptoms, and how advanced the ALS is at the time of depression screening. Depression scales that emphasize the physical symptoms of depression tend to result in higher reports of depression, which may be overestimating the prevalence.7 Regardless, early detection and ongoing assessment for depression is important. Many studies describe a significant impact of depression on the quality of life in ALS, often reported to be independent of physical impairment.8
Patients with ALS and depression report less pleasure, greater suffering, weariness and anxiety, more stress, less hope, less control over illness management, and lower quality of life, and often have thoughts about ending their lives and hastening death.9 Patients with ALS may be at greatest risk of suicide at diagnosis and during the early stage of the disease.10 The occurrence of depressive symptoms in ALS seems to be predicted by the illness experience, such as delayed diagnosis and uncertainty, rather than the mental health history or traditional depression risk factors.11 Interestingly, depression does not seem to increase with disease progression or duration, and may be rare near the end of life.12
A patient's wish for suicide, hastened death through euthanasia, and physician-assisted suicide has been a focus of attention within the ALS community. Predictors of suicidal ideation among patients with ALS include feelings of hopelessness, less comfort through religion, and less optimism; however, ALS patients that wish to die are not necessarily clinically depressed.13 Also, a wish to die has not been associated with either cognitive or behavioral impairment.14 Regardless, the consequences of depression in ALS are detrimental, highlighting the essential need for careful psychological assessment throughout the disease trajectory, especially when patients begin contemplating assisted suicide or wish for a hastened death. In those circumstances, the psychological assessment should go beyond screening for depression and include an evaluation of existential suffering and end-of-life despair.13
Prevalence rates for anxiety in patients with ALS range from 0% to 30%.3 Unfortunately, the recognition of anxiety in ALS is challenging due to similar symptoms related to ALS-associated dyspnea.15 As might be expected, there tends to be a higher level of anxiety during the diagnostic phase and the early period after the formal diagnosis in both patients and their caregivers.16 There are likely several factors contributing to this heightened anxiety, including the uncertainty of the diagnosis, the implications of the diagnosis, and the impact on function, quality of life, and future planning. Medical providers should recognize this risk for increased anxiety and provide appropriate pharmacological and psychological interventions to provide some relief during this highly distressing time.16
Other Psychiatric Manifestations
Although depression and anxiety are the main psychiatric manifestations in ALS, there are other important symptoms to consider. Patients with ALS can exhibit broad psychological distress as compared to healthy people, and evidence of hostility, interpersonal sensitivity, and even paranoia has been demonstrated in some patients.17 In addition, approximately 50% of ALS patients develop cognitive and behavioral impairment arising from disease-related dysfunction in the frontal and temporal lobes. The most common impairment observed in patients with frontotemporal dysfunction is apathy, with 30% to 40% having moderate or severe apathy.18 Patients with behavioral impairment are more likely to have depressive symptoms, lower levels of positive affect and higher levels of negative affect, higher hopelessness, lower quality of life, and higher stress levels.14 This is clinically meaningful because any degree of cognitive and behavioral dysfunction is a strong predictor of poor outcomes, including reduced efficacy of life-prolonging treatments such as gastrostomy tubes and noninvasive ventilation, and even death.19 Neurobehavioral changes may also manifest as personality changes, even in the absence of obvious cognitive changes. These changes include, but are not limited to, alterations in decision-making, problem solving, affect, motivation, and other executive functions. Unfortunately, patients with ALS may not have insight into their personality changes, emphasizing the importance of gathering collateral information from friends and family.20
How to Manage Mental Health in Amyotrophic Lateral Sclerosis
According to the American Academy of Neurology (AAN), there have been no controlled trials of treatment for depression and anxiety in ALS, although a consensus among experts suggests that depression and anxiety should be treated in patients with ALS.15 Even though controlled trials are lacking, clinical experts agree that selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) are likely helpful.3 TCAs are often prescribed if the anticholinergic effects are desired for symptoms such as sialorrhea or insomnia, and SSRIs may be used when anticholinergic side effects are to be avoided or if other symptoms are present such as pseudobulbar affect. Anxiety is usually treated with anxiolytics.3,15 Despite the AAN recommendations, the treatment of depression and anxiety in ALS tends to be insufficient.3 This emphasizes the importance of routine and consistent screening as well as close monitoring of the effectiveness of pharmacologic treatments.
In addition to pharmacological treatment, psychological interventions such as cognitive-behavioral therapy have been recommended.3 Experts suggest that psychological interventions could teach ALS patients appropriate coping skills, reappraisal skills, and encourage them to engage in activities that are practical, pleasant, and provide meaning. For patients with ALS, both physical and emotional well-being are related to coping skills, which tend to change over time.21 The most commonly used coping strategies by patients with ALS tend to be using social support and maintaining independence.22 Not surprisingly, the best predictors for depression severity in ALS may be perceived social support and self-appraisal of coping potential, and the best predictor for a person's quality of life is perceived social support.23 These findings emphasize the importance of developing and using healthy coping strategies and psychological support throughout the entire disease trajectory.21 Frequent and ongoing psychological assessment of ALS patients should be standard of care.
Patient engagement in psychological interventions may become increasingly more difficult for patients with ALS due to worsening dysarthria and motor weakness making communication more challenging. Fortunately, patients can be taught to use augmentative and assistive communication (AAC) devices to maintain patient-therapist relationships as well as provide a mechanism for ongoing interaction with family and friends.24 Examples of AAC devices include voice amplifiers; speech-generating applications on smartphones, tablets, and computers; as well as eye-gaze technology that allows a patient to communicate using eye tracking software and computers. Use of AAC devices has been shown to improve symptom control, improve communication with the medical team and family, and reduce psychological distress by promoting autonomy, dignity, and self-esteem.24
Decision-Making and Cognitive Impairment
Patients with ALS face many clinical decisions throughout the course of their disease due to the complex and changing nature of ALS. Current models for decision-making in chronic illness may not be sufficient for patients with ALS.25 Patient-centered decision-making strategies that involve caregivers, provide the right amount of information, and support deliberation and implementation may help improve decision-making for these patients.25 However, even under ideal circumstances, disease-related factors such as physical disability and executive dysfunction may influence acceptance or refusal of interventions.26 The loss of a future and the feeling of being a burden to family are predictors for decisions against life-prolonging treatments such as gastrostomy and noninvasive ventilation.27 Furthermore, the cognitive effects of frontotemporal dysfunction on decision-making capacity in ALS patients are not clear, although it can compromise medical decision-making capacity.28 Early detection and regular assessment of cognitive deficits can improve care by making the patient more proactive and leading to earlier end-of-life discussions. Preserving patient choices can help safeguard autonomy and retain dignity.28
Supporting the Mental Health of the Caregiver
The effects of mental health go beyond the patient with ALS. There is a strong correlation between depression and anxiety of patients with that of the caregivers. This correlation is strongest in older caregivers.29 The emotional burden of caring for a person with ALS can be substantial. Studies have shown that there is a strong relationship between the patient and caregiver level of distress, which suggests that attention to the mental health needs of a caregiver may improve the patient's distress as well.30 Strategies to address these effects on caregivers and providers focus on finding positive meaning in providing the care. In addition, providing support to the caregiver on an individual basis as well as coupled with the ALS patient can be beneficial.31 It is important for caregivers and providers to maintain their own physical and emotional health through engaging in meaningful experiences and hobbies, and preserving relationships with others.31 Educational programs for caregivers are lacking and should be a focus of future research.
Summary and Conclusions
ALS is a devastating neurodegenerative disease that requires comprehensive physical and psychological care. Patients with ALS may not be at a greater risk for mental health disorders, but they are at great risk for serious consequences when they do occur. The impact of unrecognized and untreated depression, anxiety, and other mental health conditions can lead to increased morbidity, mortality, and overall worsening of quality of life. These patients require careful mental health monitoring throughout the course of their illness, especially at the beginning. Although rigorous trials for the treatment of mental health disorders are lacking, a combination of pharmacological and psychological interventions are recommended and should be standard of care.
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- Ringholz GM, Appel SH, Bradshaw M, Cooke NA, Mosnik DM, Schulz PE. Prevalence and patterns of cognitive impairment in sporadic ALS. Neurology. 2005;65:586–590. doi:10.1212/01.wnl.0000172911.39167.b6 [CrossRef].
- Kurt A, Nijboer F, Matuz T, Kubler A. Depression and anxiety in individuals with amyotrophic lateral sclerosis: epidemiology and management. CNS Drugs. 2007;21:279–291. doi:10.2165/00023210-200721040-00003 [CrossRef]
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- Thakore NJ, Pioro EP. Depression in ALS in a large self-reporting cohort. Neurology. 2016;86:1031–1038. doi: http:/?/?dx.?doi.?org/?10.?1212/?01.?wnl.?0000503501.?75283.?f1. doi:10.1212/WNL.0000000000002465 [CrossRef]
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- Ferentinos P, Paparrigopoulos T, Rentzos M, Zouvelou V, Alexakis T, Evdokimidis I. Prevalence of major depression in ALS: comparison of a semi-structured interview and four self-report measures. Amyotroph Lateral Scler. 2011;12:297–302. http://dx.doi.org/10.3109/17482968.2011.556744 doi:10.3109/17482968.2011.556744 [CrossRef]
- Korner S, Kollewe K, Abdulla S, Zapf A, Dengler R, Petri S. Interaction of physical function, quality of life and depression in Amyotrophic lateral sclerosis: characterization of a large patient cohort. BMC Neurol. 2015;15:84. doi:10.1186/s12883-015-0340-2 [CrossRef].
- Rabkin JG, Goetz R, Factor-Litvak P, et al. Depression and wish to die in a multicenter cohort of ALS patients. Amyotroph Lateral Scler Frontotemporal Degener. 2015;16:265–273. doi:10.3109/21678421.2014.980428 [CrossRef].
- Fang F, Valdimarsdottir U, Furst CJ, et al. Suicide among patients with amyotrophic lateral sclerosis. Brain. 2008;131:2729–2733. doi:10.1093/brain/awn161 [CrossRef].
- Caga J, Ramsey E, Hogden A, Mioshi E, Kiernan MC. A longer diagnostic interval is a risk for depression in amyotrophic lateral sclerosis. Palliat Support Care. 2015;13:1019–1024. doi: https://doi.org/10.1017/S1478951514000881. doi:10.1017/S1478951514000881 [CrossRef]
- Rabkin JG, Albert SM, Del Bene ML, et al. Prevalence of depressive disorders and change over time in late-stage ALS. Neurology. 2005;65:62–67. doi:10.1212/01.wnl.0000167187.14501.0c [CrossRef].
- Albert SM, Rabkin JG, Del Bene ML, et al. Wish to die in end-stage ALS. Neurology. 2005;65:68–74. doi:10.1212/01.wnl.0000168161.54833.bb [CrossRef].
- Rabkin J, Goetz R, Murphy JM, Factor-Litvak P, Mitsumoto HALS COSMOS Study Group. Cognitive impairment, behavioral impairment, depression, and wish to die in an ALS cohort. Neurology. 2016;87:1320–1328. doi:10.1212/WNL.0000000000003035 [CrossRef].
- Miller RG, Jackson CE, Kasarskis EJ, et al. Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: multidisciplinary care, symptom management, and cognitive/behavioral impairment (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2009;73:1227–1233. doi:10.1212/WNL.0b013e3181bc01a4 [CrossRef].
- Vignola A, Guzzo A, Calvo A, et al. Anxiety undermines quality of life in ALS patients and caregivers. Eur J Neurol. 2008;15:1231–1236. doi:10.1111/j.1468-1331.2008.02303.x [CrossRef].
- Felgoise SH, Chakraborty BH, Bond E, et al. Psychological morbidity in ALS: the importance of psychological assessment beyond depression alone. Amyotroph Lateral Scler. 2010;11:351–358. doi:10.3109/17482961003667630 [CrossRef].
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- Garcia Perez AI, Dapueto JJ. Case report of a computer-assisted psychotherapy of a patient with ALS. Int J Psychiatry Med. 2014;48:229–233. doi:10.2190/PM.48.3.g [CrossRef].
- Hogden A, Greenfield D, Nugus P, Kiernan MC. Development of a model to guide decision making in amyotrophic lateral sclerosis multidisciplinary care. Health Expect. 2015;18:1769–1782. doi:10.1111/hex.12169 [CrossRef].
- Martin NH, Landau S, Janssen A, et al. Psychological as well as illness factors influence acceptance of non-invasive ventilation (NIV) and gastrostomy in amyotrophic lateral sclerosis (ALS): a prospective population study. Amyotroph Lateral Scler Frontotemporal Degener. 2014;15:376–387. doi:10.3109/21678421.2014.886700 [CrossRef].
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- Chen D, Guo X, Zheng Z, et al. Depression and anxiety in amyotrophic lateral sclerosis: correlations between the distress of patients and caregivers. Muscle Nerve. 2015;51:353–357. doi:10.1002/mus.24325 [CrossRef].
- Rabkin JG, Wagner GJ, Del Bene M. Resilience and distress among amyotrophic lateral sclerosis patients and caregivers. Psychosom Med. 2000;62:271–279. doi:10.1097/00006842-200003000-00020 [CrossRef]
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