Table 1.

Non-motor symptoms and potential treatments in ALS

Symptom	Details	Reported prevalence	Non-pharmacological interventions	Pharmacological interventions	References
Neuropsychiatric	Depression	Depression 0–44%	Talking therapies	Benzodiazepines and other anxiolytic medications	[46, 51–54]
	Anxiety	Anxiety 0–33%	Music therapy	Antidepressants (particularly the SSRI and TCA groups)
	Suicidal ideation	Suicidal ideation 13.3%	Hypnosis	Dextromethorphan and quinidine combination for emotional lability
	Emotional lability	Emotional lability 50%	Mindfulness	Amitriptyline due to additional anticholinergic effects on excessive saliva and insomnia
			Cognitive behavioural therapy
Cognitive impairment	Executive dysfunction Social cognition Verbal fluency	30–50% of pwALS have some level of cognitive impairment	Trial of non-invasive ventilation (NIV) to evaluate if cognitive problems may be related to respiratory impairment	No medications to address AL specific cognitive impairment currently available Cognitive status must also be considered in prescribing symptom management drugs	[8, 10, 55–57]
	Working memory Language dysfunction	6–14% of pwALS reach threshold for FTD		Glycopyrrolate as first option of treating sialorrhea in pwALS with cognitive impairment as this has fewer central nervous system side effects
Behavioural change	Apathy Impulsivity Disinhibition Perseveration Loss of Sympathy/empathy Hyper-orality and change in eating behaviour	24–69% of pwALS experience some behavioural change Apathy is most common behavioural change, experienced by 28% of pwALS	No ALS-specific but FTD interventions available which may be beneficial  Environmental management (reducing noise, clutter and stimuli and avoiding potentially problematic situations)  Non-verbal cues  Creating reward systems	Benzodiazepines	[55, 56, 58]
Pain	Spasticity Cramps Joint immobility Pressure sores	Up to 57% of people with ALS report pain	Exercise programmes (physiotherapy)	Cramps  Quinine  Levetiracetam  Mexiletine Spasticity  Nonsteroidal anti-inflammatories  Muscle relaxants  Baclofen, tizanidine or dantrolene  Intrathecal baclofen	[10, 46, 59–61]
Sleep disturbances	Poor quality sleep Difficulty getting to, or staying, asleep Daytime sleepiness	Exact prevalence unknown due to multiple potential aetiologies of sleep problems but 45–60% of pwALS report disturbed sleep due to breathing problems	Non-invasive ventilation	Amitriptyline (antidepressant with additional benefit of insomnia management) Sedatives (opioids and benzodiazepines)	[10, 62–65]
Fatigue	Mental fatigue Physical fatigue	44% of pwALS experience clinically significant fatigue and this is associated with disease severity	Resistance exercise Respiratory exercise Repetitive transcranial magnetic stimulation (rTMS)	Modafinil	[8, 10, 66, 67]
Saliva	Excessive oral secretion Dry mouth	Problematic saliva 37.5%	Radiotherapy Suction Humidification of NIV	Hyoscine patches Amitriptyline Atropine drops Glycopyrrolate Carbocisteine Botulinum toxin	[8, 10, 46, 68, 69]