Post-Stroke Fatigue Evidence Tables and Reference List
Post-stroke fatigue (PSF) is known to occur commonly, is associated with mood disorders and pain, and negatively impacts recovery. Persons experiencing PSF report common experiences including having less capacity and energy, an abnormal tiredness and an overwhelming need for long-lasting sleep, being easily fatigued, fatigue for which there was no obvious cause or explanation and increased stress sensitivity (Eilertsen et al. 2013).
The incidence of post-stroke fatigue is difficult to estimate given that many patients report symptoms of pre-stroke fatigue (Lerdal et al. 2011). Estimates of incidence/prevalence also vary depending on when fatigue is assessed in the recovery process and which tool is used for assessment. At the time of admission to inpatient rehabilitation, fatigue was present in 51.5% of patients (Schepers et al. (2006) and at the point of discharge, in 58.3% of patients (Van Eijsden et al. 2012). Schepers et al. (2006) reported that fatigue was present in 64.1% and 69.5%, respectively at 6 months and 1 year. Overall, fatigue was present in 37.7% of patients and absent in 17.4%, at all assessment points. Of the patients reporting fatigue at 1 year, 29.3% were also depressed. Van der Port et al. (2007) reported that the percentages of patients considered fatigued at 6, 12 and 36 months were 68%, 74% and 58%, respectively, in 223 acute stroke patients followed prospectively. In all of these studies, the presence of fatigue was identified based on a score of 4 or greater on the Fatigue Severity Scale. Parks et al. (2012) reported that of 228 participants who were surveyed 12 months post stroke, 37% reported symptoms of fatigue at least once during the previous month. Among those reported fatigue, 59.5% stated that fatigue was one of the worst or the worst symptom they experienced. Two years following stroke, of 5,189 patients who were alive and included in the Riks-Stroke national stroke registry, 10% and 29.2% of respondents reported “always” or “often” being tired (Glader et al. 2002) in a postal survey. The clinical course of PSF is unclear; therefore it’s even unknown if PSF increases or decreases over time. Snaphaan et al. (2011) reported that the prevalence of fatigue was 35% at 2 months post stroke and 33% at 18 months. 26% of patients reported fatigue at both assessment points, while 9% reported fatigue at baseline but not at follow-up, and 8% reported no fatigue at baseline but did at follow-up. In a systematic review (Duncan et al. 2012), which included the results of 9 studies, the percentage of patients reporting fatigue increased from assessment time 1 to time 2, while it had decreased between assessment points in 2 studies. Independent predictors of fatigue that have been identified include depression, low levels of physical functioning, and pre-stroke fatigue (Lerdal et al. 2011). Predictors of fatigue are somewhat unclear as both increasing (Snaphaan et al. 2011) and decreasing age (Parks et al. 2012), have been reported as predictors of PSF, as have female (Schepers et al. 2006) and male (Gladder et al. 2002) sex.
A few controlled studies have been conducted comparing fatigue in persons recovering from stroke with persons from the general population and in cases of TIA. When compared with 1,069 person of similar ages selected from the general population, the fatigue scores of 165 patients with acute stroke were significantly higher after adjusting for age, sex and living arrangements. Of the 5 subscale components of the Multidimensional Fatigue Inventory (MFI-20), stroke patients had significantly higher general and physical fatigue scores and also higher reduced activity scores at 3 months (Christensen et al. 2008). Winward et al. (2009) compared 73 subjects with minor stroke and 76 subjects with TIA who were participants in the Oxford Vascular study. At 6 months, a higher proportion of participants with stroke reported significant fatigue, assessed using the Chalder Fatigue Scale (56% vs. 29%, p=0.008). A higher proportion of subjects with stroke, who had initial NIHSS scores of 0 reported significant fatigue compared with TIAs with initial NIHSS scores of 0 (57% vs. 29%, p=0.015). Subjects who felt they had not made a full recovery were more likely to be fatigued compared to those who felt they had (72% vs. 23%, p<0.0001).
There are few treatments for post-stroke fatigue that have been evaluated. A Cochrane review (McGeough et al. 2009) included the results from 3 RCTs, each examining different therapy approaches. The results from all 3 were equivocal. In one trial, 83 subjects with post-stroke emotional disturbances, an average of 14 months after stroke onset, were randomized to receive 20 mg/day of fluoxetine (n=40) or placebo, (n=43) for 3 months (Choi-Kwon et al. 2007). At the end of treatment, there were no significant differences in the number of patients with PSF. At 6 months, 34 patients (85%) in the fluoxetine group reported PSF compared with 40 (93%) in the control group. However, at 3 months, fewer patients in the fluoxetine group reported excessive/inappropriate crying (n=16, 40% vs. n=27, 62.8%, p=0.038), and at 6 months fewer patients in the fluoxetine group were identified with depression (n=5, 12.5% vs. n=13, 30.2%, p=0.05). In another trial, 831 participants with a variety of chronic disease conditions who may or may not have suffered from fatigue at study entry were randomized to participate in a 6-month chronic disease self-management program (CDSMP) immediately after randomization, or after a 6 month delay (Lorig et al. 2001). The program was provided over 7 weeks, for 2.5 hours weekly. The authors acquired data reporting on the subset of 125 patients with stroke in the trial. The mean fatigue scale change scores (1-5) at 6 months were 0.246 for controls and 0.087 for those who received the active treatment condition, indicating that fatigue became worse for wait list controls, although the difference was not signiﬁcant (p=0.253). Finally, in the third study, 31 women in the acute stage of SAH who may or may not have suffered from fatigue were randomized to receive tirilazad mesylate vs. placebo for 10 consecutive days. In women who survived and could be assessed for fatigue at 3 months, significantly fewer patients in the intervention group reported debilitating fatigue (4/9 vs. 9/9, p<0.01).
Two RCTs that evaluated therapy programs designed specifically to treat fatigue following stroke reported significant improvements in symptoms. Zedlitz et al. (2013) randomized 83 participants with severe fatigue >4 months post stroke to participate in a 12-week program consisting of group cognitive treatment (control condition) or group cognitive treatment combined with graded activity training (COGRAT). Cognitive treatment consisted of cognitive behavioural therapy and compensatory strategy teaching. Those in the COGRAT group also received 24 sessions, each 2-hours in duration of graded activity training, including treadmill walking, strength training, and homework assignments. Participants who received COGRAT were significantly more likely to experience clinically relevant improvement in fatigue severity (57.9% vs. 24.4%, p=0.002). Johansson et al. (2012) randomized 29 patients, of whom 18 were recovering from stroke (11 from traumatic brain injury) with mental fatigue to participate in an 8-week program of Mindfulness–Based Stress Reduction (MBSR), which included yoga, body scan, and sitting meditation, or to a wait list control group. Compared with those in the wait-list control group, participants who received the MBSR program immediately reported a significantly greater decrease in Mental Fatigue Scale scores.