41 - Fatigue

Fatigue

Drug treatment of psychiatric symptoms in the context of other conditions CHAPTER 10 ­published trials, but risperidone or clozapine has been recommended because of the low risk of extrapyramidal symptoms.55 On this basis, olanzapine, aripiprazole and ­quetiapine might also, in theory at least, be possible options. ECT has been used in refractory cases.56 Risperidone, quetiapine, olanzapine and, particularly, clozapine may have ­beneficial immunomodulatory properties.57 Psychosis may rarely be the presentation of an MS relapse in which case steroids may be beneficial but would need to be given under close supervision. Note also the small risk of psychotic reactions in patients receiving tetrahydrocannabinol (THC)-­containing formulations.58,59 Cognitive impairment Cognitive impairment occurs in at least 40–65% of people with MS. Some of the medications commonly prescribed can worsen cognition, such as tizanidine, diazepam and ­gabapentin.60 Although there are no published trials, evidence from clinical case studies suggests that the treatment of sleep difficulties, depression and fatigue can enhance cognitive function.60 There have been two small trials with donepezil for people with mild to moderate cognitive impairment showing moderate efficacy.61,62 A larger study found no effect.63 Similarly, data supporting the use of memantine are weak.64 Overall, no treatment has proven worthwhile efficacy65 and disease-­modifying agents offer greater promise.66 Fatigue Fatigue is a common symptom in MS, with up to 80% of people affected.67 The aetiology of fatigue is unclear but there have been suggestions that disruption of neuronal networks,68 depression or psychological reactions,55 sleep disturbances, inflammation69 or medication may play a role in its development. Pharmacological and non-­ pharmacological strategies67 should be used in a treatment strategy. Non-­pharmacological strategies include reviewing history for any possible contributing factors, assessment and treatment of underlying depression if present, medication, pacing activities and appropriate exercise. One trial suggests that CBT reduces fatigue scores.70 Pharmacological strategies include the use of amantadine71 or modafinil. In the UK, National Institute for Health and Care Excellence (NICE) guidelines suggest no medicine should be used routinely but that amantadine could have a small benefit and should be offered.72 A Cochrane review of amantadine in people with MS suggested that the quality and outcomes of the amantadine trials are inconsistent and that therefore efficacy remains unclear.71 A meta-­analysis of 11 RCTs found supporting data for amantadine73 and a later (2020) meta-­analysis confirmed its value.74 Modafinil has mixed results in clinical trials, but a meta-­analysis of five RCTs75 found clear benefit. Despite doubts over its efficacy, modafinil is widely used in MS.76 A 2023  meta-­analysis of five studies suggested benefit for vitamin D supplementation.77