Authors' objectives: To determine whether there is any evidence on the efficacy/effectiveness of Vyvanse® or lisdexamfetamine in treating chronic fatigue syndromes (CFS) or Post-Acute COVID-19 Syndromes (PACS).

Authors' results and conclusions: Ten published studies were identified from the literature searches. Upon examining the titles and abstracts of these ten studies, four studies were thought to be relevant and were retrieved in full for further appraisal. Of the four studies that were retrieved in full, three studies did not provide any data or were not relevant to the objective of this systematic review and will not be discussed further. Further searches on investigating the application of lisdexamfetamine in treating PACS, identified eight published studies. Upon examining the titles and abstracts of these eight studies, one study was thought to be relevant and were retrieved in full for further appraisal. Full examination on this case report (level of evidence 4) revealed a combination of pharmaceutical therapy, hence was not relevant to the objective of this systematic review and will not be discussed further. A small (n total = 26), double blind randomized controlled trial (level of evidence 1) assessing the efficacy of lisdexamfetamine dimesylate (LDX) for the treatment of executive functioning deficits in adults (ages 18–60) diagnosed with chronic fatigue syndrome(CFS) was reported. In this study, adult participants, recruited from a local advertisement along with existing patients from the clinic, aged between 18–60 years old, with CFS and cognitive complaints were included in the trial. CFS was diagnosed based on the participants’ medical history and confirmed by the primary investigator using a clinical interview, brief physical examination, consultation of Fukuda et al (1994) guidelines for CFS diagnosis, and the participant’s responses to the Chronic Fatigue Syndrome checklist. Executive functioning impairment was formally assessed using the BRIEF—A, a neuropsychological measure of executive impairment. Impairment was defined as a BRIEF— A Global Executive Composite score that was 1.5 standard deviations above the standardized population mean. Participants were block randomized to LDX or placebo using an envelope allocation method. Fifteen participants were randomly assigned to the intervention and placebo groups. Four participants were screen failures, but all had been randomly pre-assigned to the placebo group and were dropped from further data analysis. The intervention group received LDX administered as a flexible morning dose (30,50 and up to 70mg/d). It is not clear how the placebo group was treated especially on the dosing adjustment. The primary outcomes were on executive functioning impairment that was measured by the Behavior Rating Inventory of Executive Function—Adult (BRIEF—A) and fatigue, which was measured by Fatigue Severity Scale (FSS), and was considered as one of the secondary outcomes. It should be noted although the author mentioned about six total number of visits, it is not clear how long those total visits were and if there was any difference between the intervention and controls. The author reported that participants in the LDX group showed statistically significantly more positive changes in BRIEF—A scores (mean change 21.4, SD:15.9) than those in the placebo group (mean change 3.4, SD:7.3). With regard to fatigue, mean FSS change in the LDX group was 20.9 (SD:14.7) while in the placebo group was 5.0 (SD:11.7) (p=0.008). It should be noted that it was not clear how the participants were selected; there was no hypothesis with corresponding sample size calculation presented; with regard to the relatively small size of the block in the randomization procedure, potential “guessing” on the next sequence of treatment allocation was possible (hence breaking the blinding); the author did not present traditional Table 1 (on the characteristics of the study population) hence it was not possible to assess whether the randomization process worked; further, multiple statistical tests were presented without any adjustment to level of type 1 error presented. As such, the potential effect of bias, chance and confounding cannot be excluded from the reported outcomes. At present, there is one high-level low-quality evidence reporting on the efficacy of lisdexamfetamine in treating fatigue in patients diagnosed with CFS. At present, there is no study reporting the efficacy/effectiveness of lisdexamfetamine in treating patient diagnosed with PACS.

Authors' methods: A comprehensive and systematic literature search was conducted on June 17, 2025. The search was done on commercial medical literature databases using a combination of keywords. No limitations, such as on the language or year of publication, were implemented in any of these searches. A manual search was also conducted on the references of articles that were retrieved in full.

Project Status: Completed

URL for project: https://www.worksafebc.com/en/about-us/research-services/evidence-based-medicine-and-systematic-reviews

Year Published: 2025

URL for published report: https://www.worksafebc.com/en/resources/health-care-providers/guides/efficacy-effectiveness-of-vyvans-in-treating?lang=en&origin=s&returnurl=https%3A%2F%2Fwww.worksafebc.com%2Fen%2Fforms-resources%23sort%3DDate%26q%3DEfficacy%252FEffectiveness%2520of%2520Vyvanse%25C2%25AE%2520in%2520Treating%2520Chronic%2520Fatigue%2520Syndromes%2520Post%2520Acute%2520COVID-19%2520Syndromes%26f%3Alanguage-facet%3D%5BEnglish%5D%26tags%3DGuide%7C2d7eb4b30f6a4a319e0d40565c9abbab%2CHealth%2520Care%2520Provider%7C13468b0b3f074f6bade3f57ac3cdfb8e%2CSystematic%2520Review%7Cf78c29d570c14ec3b5a394385905df70&highlight=Efficacy/Effectiveness%20of%20Vyvanse%C2%AE%20in%20Treating%20Chronic%20Fatigue%20Syndromes%20Post%20Acute%20COVID-19%20Syndromes

English language abstract: An English language summary is available

Publication Type: Mini HTA

Country: Canada

Organisation Name: WorkSafeBC

Contact Address: 6591 Westminster Highway, Richmond, BC, V7C 1C6 Canada. Tel: 604-231-8417; Fax: 604-279-7698

Contact Name: ebpg@worksafebc.com

Contact Email: ebpg@worksafebc.com

Copyright: WorkSafe BC