Elsevier

The American Journal of Medicine

Volume 119, Issue 2, February 2006, Pages 167.e23-167.e30
The American Journal of Medicine

Brief observation
Does Methylphenidate Reduce the Symptoms of Chronic Fatigue Syndrome?

https://doi.org/10.1016/j.amjmed.2005.07.047Get rights and content

Abstract

Purpose

Chronic fatigue syndrome is a clinical entity consisting of prolonged and debilitating fatigue in which concentration disturbances are very frequent. Until now, no medical treatment has shown any efficacy. The objectives of this study were to investigate the short-term effects of methylphenidate, an amphetamine derivative, on fatigue, concentration disturbances, and quality of life.

Subjects and methods

A double-blind randomized placebo-controlled crossover study was conducted in 60 patients who fulfilled the 1994 Centers for Disease Control criteria for chronic fatigue syndrome and had concentration difficulties. Patients were enrolled between March 2003 and March 2004 at the outpatient department of a university hospital referral center for chronic fatigue syndrome patients. Random assignment to 4 weeks treatment with methylphenidate 2 × 10 mg/day, followed by 4 weeks of placebo treatment, or 4 weeks of placebo treatment, followed by methylphenidate treatment. Fatigue and concentration were measured with a Checklist Individual Strength (CIS) and a Visual Analogue Scale (VAS).

Results

Fatigue scores fell significantly during methylphenidate intake in comparison with baseline (mean difference: −0.7, P = .010 for VAS; mean difference: −11.8, P <.0001 for CIS) and in comparison with placebo (mean difference: −1.0, P = .001 for VAS; mean difference: −9.7, P <.0001 for CIS). Concentration disturbances, measured with a VAS improved significantly under methylphenidate treatment compared with baseline (mean difference: −1.3, P <.0001) and compared with placebo (mean difference: −1.1, P <.0001). A clinical significant effect (≥33% improvement or CIS ≤76) on fatigue was achieved in 17% of patients, who were considered responders; on concentration in 22% of patients.

Conclusions

Methylphenidate at a dose of 2 × 10 mg/day is significantly better than placebo in relieving fatigue and concentration disturbances in a minority of chronic fatigue syndrome patients. Further studies are needed to investigate the long-term effects of this treatment.

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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