Comment: The quality of evidence is downgraded by indirectness (differences in patients).
A Cochrane review [Abstract] 1 included 11 studies with a total of 1817 subjects with Parkinson's disease. Three studies included only people who experienced clinically relevant fatigue (Fatigue Severity Scale score HASH(0x2fcfe80) 4 out of 7 or Multidimensional Fatigue Inventory total score > 48 out of 100), whereas all other studies did not select participants on the basis of experienced fatigue. Nine studies investigated the effects of medication (i.e. levodopa-carbidopa, memantine, rasagiline, caffeine, methylphenidate, modafinil or doxepin) on subjective fatigue. All studies were placebo controlled. The evidence on effect of doxepin on the impact of fatigue on activities in daily life (ADL) or fatigue severity was insufficient (SMD = -1.50, 95% CI -2.84 to -0.15; one study, n = 12). Rasagiline reduced or slowed down the progression of physical aspects of fatigue (SMD = -0.27, 95% CI -0.39 to -0.16, one study, n = 1176). None of the other pharmacological interventions affected subjective fatigue. With regard to adverse effects, only levodopa-carbidopa showed an increase for the risk of nausea (RR = 1.85, 95% CI 1.05 to 3.27; one study, n = 361). There was some effect of exercise on reducing the impact of fatigue on ADL or fatigue severity (SMD = -0.45, 95% CI -1.21 to 0.32, 2 studies, n = 57).
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