Brief observationDoes Methylphenidate Reduce the Symptoms of Chronic Fatigue Syndrome?
Section snippets
Participants
The study was carried out at the general internal medicine outpatient clinic of the University Hospital Gasthuisberg, which is recognized by the Flemish Government as a reference center for chronic fatigue syndrome (ie, primary and secondary care, and not tertiary care). Most patients were referred by their general practitioner; some came without any referral.
Consecutive ambulant patients complaining of fatigue of at least 6 months’ duration were checked for underlying organic or psychiatric
Primary Outcome Measure: Fatigue and Concentration Disturbances
Two instruments were used to assess fatigue: (1) The Checklist Individual Strength (CIS)20, 21 is a self-report questionnaire that assesses the severity of fatigue over the previous 2 weeks, ranking from 20 to 140. We defined a clinically significant response as a ≥33% fall in fatigue scores or a score on the CIS ≤76, which has been defined previously as the cut-off point for probable fatigue in employees.22 Patients fulfilling these criteria were considered responders. (2) A Visual Analogue
Sample size, randomization and blinding
Before the start of the study, a power analysis was done to estimate the number of patients minimally required to detect a difference of at least 10% on any of the primary outcome measures. The participation of 54 patients was required to detect such a difference with 90% certainty, using a double-sided significance level of 5%. Anticipating a dropout rate of 10% during the study, 60 patients were randomized by computer software, designed by the hospital pharmacy, which generated the
Statistical analysis
Statistical analyses were conducted using the Statistical Package for the Social Sciences (SPSS 12.0 for Windows, Chicago, Ill). Descriptive statistics were calculated for all patient characteristics and variables at baseline. The Missing Value Analysis (MVA) procedure describes the pattern of missing data, estimates means, standard deviations, covariances, and correlations (SPSS Missing Value Analysis 12.0 for Windows, Chicago, Ill). MVA with an expectation-maximization (EM) method was used to
Results
Figure 1 shows the flow of the participants through the trial. Between March 24, 2003 and March 15, 2004, 180 patients with a diagnosis of chronic fatigue syndrome were seen at the Internal Medicine Outpatient Department. Inclusion criteria were not met in 85 patients because of the following reasons: antidepressant therapy in 75 patients, other therapy aimed to improve fatigue in 6 patients, no concentration difficulties in 2 patients, pregnancy in 1, and 1 patient was under 18 years of age.
Discussion
Methylphenidate (20 mg/day for 4 weeks) significantly improved fatigue and concentration disturbances in patients with chronic fatigue syndrome compared with placebo-treatment. There was a significant effect on fatigue on both outcome instruments (VAS and CIS). The effect of methylphenidate was significant on all of the CIS subdimensions except for activity. Concentration disturbances measured with a VAS had also significantly improved after methylphenidate. A clinically significant response
Acknowledgments
The authors express their great gratitude to Mrs. Helga Keunen and Marina Lejeune, study nurses, for their valuable help in performing the study and collecting the outcome data.
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