This information is for health professionals and service providers.
Fatigue and insomnia are common symptoms experienced by people living with MND which may impact significantly on their quality of life.
A number of symptoms of MND, as well as pre-existing conditions, stress and anxiety, may cause fatigue and insomnia. Careful monitoring and regular review is therefore important to ensure early intervention, optimal symptom management and appropriate support.
It is common for the person's carer to also experience fatigue and insomnia. Carer wellbeing is an integral part of multidisciplinary care and support.
Fatigue (tiredness) is a common symptom of MND. It is caused by a number of factors:
People living with ALS/MND often experience fatigue, which can cause distress and reduce quality of life. Fatigue can have many causes, including respiratory problems, medication, malnutrition, and depression.
Implications for practice
There is very limited and low‐quality evidence from randomised controlled trials (RCTs) about treatment to reduce fatigue in amyotrophic lateral sclerosis/motor neuron disease (ALS/MND). Therefore, it is uncertain whether modafinil, breathing exercises, resistance exercise, or repetitive transcranial magnetic stimulation (rTMS) are of benefit.
Implications for research
Despite the prevalence of fatigue in ALS/MND, we lack high‐quality RCTs that evaluate interventions to improve this disabling, but potentially treatable symptom. There is a need for considerable further work to identify an effective treatment for fatigue for people with ALS/MND. Three studies demonstrated very low quality evidence of benefit for modafinil, inspiratory muscle training, and rTMS, which may merit further investigation. Unfortunately, the positive effects of rTMS were short lived, and no longer detected two weeks after treatment cessation. Although the effect of modafinil and respiratory exercise is very uncertain, as the quality of the evidence is very low, they appear to have the greatest potential as an effective treatment for fatigue in ALS/MND (Gibbons et al 2018).
Insomnia and fatigue are common and impact on quality of life. In one small study modafinil was found to improve symptoms of fatigue but larger studies are required. There have been no studies of interventions for insomnia and therefore standard treatments, hypnotics (mirtazapine and amitritypline) are recommended (Hobson and McDermott 2016).
Fatigue is reported in 44–83% of patient with ALS and likely is multifactorial with sleep disruption, nocturnal complaints such as nocturia and cramps, nutritional status, weakness, vital capacity, functional status, depression, and medications including riluzole all potentially playing a role. (McElhiney 2009, LoCoco 2012, Ramirez 2008, Bensimon 1994) In a given patient, it may be challenging to tease out the biggest contributors, but treating those that are readily identified to see if fatigue improves is a practical approach. Overall and physical fatigue but not mental fatigue was found more often in ALS patients compared to controls. (Lou J-S 2003) Modafinil in doses ranging from 100 to 300 mg daily in a placebo controlled trial for 4 weeks resulted in a statistically significant improvement in the Clinical Global Impression score (the study’s primary endpoint) in 19/25 on active drug and in 1/7 on placebo (p=0.003) as well as improvement on the Visual Analogue Scale (VAS) for energy (p=0.039) and the VAS for stamina (p=0.009) but not in the Fatigue Severity Scale (p=0.066. (Rabkin 2009) (Jackson et al 2015).
Causes of insomnia include:
Additionally, because breathing cannot be controlled voluntarily when sleeping, weakened muscles may lead to ineffective breathing (nocturnal hypoventilation). Sleep apnoea is the temporary cessation of breathing while sleeping. This may cause wakefulness, as the disruption of the oxygen supply wakes the person to resume normal breathing.
Sleep disturbances with MND are common and it is therefore important that the impact of MND on a person’s sleep is assessed and reviewed regularly. Optimal symptom management and a palliative, coordinated multidisciplinary team approach to care are crucial in managing the physical and psychological impacts of MND associated with sleep disturbances.
Carers may also be experiencing sleep disturbances and need support. It can help carers to:
Sleep disturbances are common in patients with ALS and significantly add to the individual burden of disease. Major causes comprise sleep-disordered breathing, immobilization, muscle cramps, RLS, and other painful or unpleasant sensations which are mostly attributable to progressive impairment of motor function. Sleep-related symptoms have to be actively asked for, and treatable conditions should be treated in order to improve well-being and quality of life. Apart from clearly physical causes of sleep disruption, psychological aspects such as fear, depression, or recurrent grief and despair have to be acknowledged and may significantly contribute to insomnia in patients with ALS. With regard to disease-specific characteristics of sleep composition and regulation, future research will extend preliminary evidence from recent studies suggesting that motor control during REM sleep, sympathovagal balance, and central respiratory control may all be altered in patients with ALS, possibly contributing to sleep disruption already in early stages of the disease (Boentert 2020).
Sleep disordered breathing (SDB) is an umbrella term which includes various separate disorders in which abnormal respiratory events occur during sleep, which are associated with adverse clinical outcomes. Due to early involvement of respiratory muscles in MND, SDB occurs at a higher frequency than compared to the general population. It significantly impacts upon patients’ quality of life and survival and its presence may predict prognosis. SDB usually precedes daytime respiratory symptoms and chronic respiratory failure. Managing SDB in MND with NIV improves quality of life and survival. Early identification and management of SDB in patients with MND is therefore crucial (D’Cruz et al 2018).
Sleep disorders are a common and can be an early manifestation of ALS, but may go undetected until the later stages of disease. Abnormal breathing during sleep is frequently present and may occur even in patients with normal respiratory function and no signs of diaphragmatic denervation. Various studies have reported obstructive and central apneas as well as non-obstructive hypoventilation in patients with ALS.
Other factors can also produce sleep disturbance, including restless legs syndrome, depression and anxiety, pain, difficulty changing position due to muscle weakness, excessive secretions and increased myoclonic activity disturbing sleep.
The impact of motor symptoms on sleep should not be underestimated. Symptoms include immobility and nocturnal cramps which are often refractory to treatment. Discomfort may also arise from excess saliva and cough, which may be ameliorated in some patients by NIV.
Amyotrophic lateral sclerosis represents a multi-faceted disorder of multiple genetic preponderance, with disturbance of respiratory function and sleep a key component and early indicator of respiratory compromise. Prompt, close management of these changes can improve both quality of life and survival, often requiring recruitment of multiple disciplines in order to optimize care (Ahmed et al 2016).
Sleep disruption in patients with ALS is frequently multifactorial in etiology and may be due to respiratory muscle weakness, difficulty re-positioning in bed, anxiety, depression and pain. Nocturnal hypoventilation results in frequent arousals and decreased total sleep time resulting in daytime fatigue and poor concentration. Overall, impaired sleep can markedly affect QoL and likely impact prognosis .
Available solutions to address impaired sleep are as varied as the diverse issues causing it. Simple physical adaptations such as an electric hospital bed can be ideal to enhance mobility and positioning. An alternating pressure air mattress or gel overlay mattress can lessen the discomfort from limited mobility. Noninvasive positive pressure ventilation can significantly affect respiratory hygiene and improve sleep quality. Antidepressant medications are also effective at reducing anxiety, depression and promoting sleep. In that regard, mirtazapine (15mg qhs) can be especially helpful. At higher doses (≥ 30 mg) mirtazapine may have a confounding effect due to enhancement of its noradrenergic effect. The anticholinergic action of the tricyclic antidepressant group can also be especially helpful, particularly in patients with sialorrhea.
Anxiolytic medications such as benzodiazepines, used specifically to induce sleep, can be helpful when used selectively. Zolpidem tartrate (10mg qhs) is often effective and preferred due to the low risk of respiratory depression. Pharmacological tolerance and withdrawal symptoms can become evident, however, with chronic use. Addressing the underlying cause of such anxiety (depression, fear, pain etc) is a preferred method of treatment.
Alternative pharmacologic agents such as melatonin, passionflower, lavender, and hops have been effective for individual patients, however, their benefits are quite variable and untested (Jackson et al 2015).
Shoesmith et al 2021, Canadian best practice recommendations for the management of amyotrophic lateral sclerosis - See table 1: symptom management recommendations
Andersen et al 2012, EFNS guidelines on the Clinical Management of Amyotrophic Lateral Sclerosis (MALS) – revised report of an EFNS task force - Insomnia and fatigue recommendations:
1. Treat insomnia with amitriptyline, mirtazapine or appropriate hypnotics (e.g. zolpidem) (GCPP).
2. For debilitating fatigue, modafinil may be considered (level A).
MND Aware e-training program MND Hub – online training course for health professionals and service providers developed by MND NSW – Session 19: Symptom management - fatigue and insomnia
International Alliance of ALS/MND Association, 17th Allied Health Professionals Forum 2019:
MND Australia 2021, End of life care: A guide for people living with MND
MND Australia Blog: Explainer: Sleep and MND
Health Talk - healthtalk.org - stories collected by academic researchers who interview people in their own homes, using their own words:
ALS Association, FYI - minimising fatigue