Gaps in the Evidence
Fatigue as a multifactorial construct: Despite fatigue being prevalent in people with SCI, the limited number of studies where fatigue is a primary or secondary outcome measure could be due to its multifactorial nature including the influence of co-morbidities. In a multiple regression analysis, Craig et al. (2013) found that people with SCI who had high levels of pain were nine times more likely to have elevated fatigue (P < 0.001), and that all of their participants who had depressive mood also suffered from fatigue whereas none of the participants with low levels of fatigue suffered from depressive mood (P < 0.001). Furthermore, Craig et al. (2013) also found that pain and depressive mood contributed, significantly and independently, almost 20% and 10% of the variance to chronic fatigue presentation in their participants with SCI (R = 0.82, R2 = 0.67; pain β = 0.52, 95% CI = 0. 34, 0.69, t (67) = 6.1, sr = 0.43, sr2 = 18,5%, P < 0.001; depressive mood β = 0.40, 95% CI = 0.22, 0.58, t (67) = 4.7, sr = 0.33, sr2 = 10.9%, P < 0.001) (Craig et al. 2013). These results are in line with those of the recent systematic review and meta-analysis of Onate-Figuérez et al. (2023) who, as discussed below, found a significant pooled association between fatigue and 12 separate factors.
Relationship between sleep factors and fatigue in SCI: None of the included RCTs investigated or measured sleep quality or presence of sleep disorders in participants. It is well-known that sleep-disordered breathing occurs more frequently in people with SCI, particularly in those with higher-level injuries; prevalence estimates are that sleep-disordered breathing is present in 60% of people with motor complete tetraplegia (Chiodo et al. 2016; Proserpio et al. 2015). If the included studies had asked participants about their sleep quality or the presence of sleep-disordered breathing, it could have been accounted for as a factor, analyzed to assess any differences between the randomized groups at baseline or post-intervention, or to help differentiate between primary and secondary fatigue. Primary fatigue more commonly describes fatigue that is resolved by a proper night’s sleep, whereas secondary fatigue, typically experienced by those with neurological disorders, is not accompanied by a desire to sleep, symptoms are not resolved by sleeping, and the fatigue is caused by an underlying medical condition generally lasting longer than one month (Levine & Greenwald 2009; Rosenthal et al. 2008).
Relationship between medications and fatigue in SCI: None of the RCTs included discussed the effects of medications or established what baseline at baseline participants were currently taking. Sedating medications are frequently prescribed to people with SCI to help manage spasticity, mental health issues, or pain; among the medications that may induce feelings of fatigue that people with SCI commonly take include baclofen, benzodiazepines, opioids, tizanidine, gabapentin, amitriptyline, and nortriptyline (Fawkes-Kirby et al. 2008). In a retrospective chart review, Lee et al. (2010) found that 52% of participants with SCI had clinical levels of fatigue, 41/147 medications that they were taking were identified to be causing fatigue, and the medications were usually antispasticity or analgesic medications. Similarly, Fawkes-Kirby et al. (2008) found that people with SCI taking two or more prescriptions from these categories scored significantly worse on the FSS, indicating higher levels of fatigue. Future studies should consider documenting the current medications their participants are currently taking so that effects can be factored in and/or accounted for.
