Letters to the Editor: Letters & Announcements
To the Editor:
In the April, 2004 issue, Larijani et al. (1) reported that modafinil significantly improved recovery after anesthesia. A pilot questionnaire study provided baseline data, while the study involving modafinil used a randomized, double-blind, placebo-controlled design. Modafinil is indicated for the use to improve wakefulness in patients with excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome (OSA/HS), and shift work sleep disorder (2).
Both studies used a self-designed questionnaire that did not undergo validation procedures. The sample size, with 17 patients receiving modafinil, is small for the claims made that patients can “significantly benefit,” and without any data, “multiple dosing may be needed.” The numerical scale (not a VAS) that was used is a nonparametric scale and “Student’s t-test” is inappropriate. While a power analysis is reported in the Study 2 methods, the results or description are not provided.
Adding to the difficulties of the study, moderate to severe “fatigue” and “feeling worn out” were less with modafinil, while moderate to severe “exhaustion” was equivalent to placebo. We cannot find a semantic reason for this inconsistency, adding to the difficulty of using an invalid instrument. An ad hoc term, “postoperative distress,” does not report a statistical test despite claiming a significant finding.
In the discussion, the authors claim placebo patients had more difficulty remaining asleep on the first night, but the ratings for “ease of sleep” show no difference. In conclusion, the authors state modafinil improves feelings of alertness and energy, but alertness was not measured by their scale and the “energy” scale shows no difference between the groups (modafinil change = −1.3; placebo change = −1.6, not significant).
Finally, and of some concern, 12% of modafinil patients complained of “restlessness,” whereas the difference with placebo in the modafinil Phase III trial is only 2% (2). As severe paranoid reactions have been reported with modafinil, an increase in side effects following residual chemically induced unconsciousness for general anesthesia provides ample opportunity for study but hardly prescriptions for use or “multiple doses.”
Keith E. Frazer, DO
Jose Valle, MD
Henry L. Bennett, PhD
Department of Anesthesiology
University of Medicine and Dentistry of New Jersey
1. Larijani GE, Goldberg ME, Hojat M, et al. Modafinil improves recovery after general anesthesia. Anesth Analg 2004;98:976–81.
2. Provigil (modafinil)[package insert], West Chester, PA, Cephalon, Inc, 1999.