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Melatonin for Chronic Whiplash Syndrome with Delayed Melatonin Onset

Randomised, Placebo-Controlled Trial

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Abstract

Objective

To assess the influence of melatonin in patients with chronic whiplash syndrome and delayed melatonin onset.

Design

Randomised, double-blind, placebo-controlled, parallel-group trial. One-week baseline was followed by a 4-week treatment period with either melatonin or placebo. In the baseline week and in the fourth treatment week sleep, degree of feeling refreshed in the morning, and pain in the neck and head were recorded daily in a diary. Sleep was also recorded by actigraphy and polysomnography. Dim-light melatonin onset (DLMO) was measured in saliva. Quality of life, cognitive processing speed and vigilance were assessed with the Medical Outcome Study Short Form-36 (MOS SF-36) questionnaire, simple and opposite reaction time tasks, and the Macworth Clock-Test.

Setting

Sleep centre and department of neurology outpatient clinic.

Patients

81 chronic whiplash syndrome patients with delayed melatonin onset. Mean (±SD) age 33.4 (±10.7) years and mean trauma-treatment interval 25.7 (±16.5) months.

Interventions

Melatonin 5mg, administered 5 hours before individual melatonin onset, or placebo.

Main Outcome Measures

Differences in change of mean between the two treatment groups as to diary sleep onset, sleep latency and sleep duration, feeling refreshed in the morning, melatonin onset, actigraphic sleep onset, polysomnographic sleep architecture, cognitive processing speed and vigilance.

Results

Mean (±SD) baseline DLMO occurred at 11.13pm (±1:18h) in the melatonin treatment group and at 11.24pm (±1:15h) in the placebo group. Melatonin treatment advanced melatonin onset [analysis of variance (ANOVA) F = 5.66, degrees of freedom (df) 1, p = 0.021] and actigraphically-registered wake-up time (ANOVA F = 6.68, df 1, p = 0.015). In the subgroup of chronic whiplash syndrome patients with melatonin onset between 10.30pm and 1.00am, melatonin also advanced diary lights-off time (ANOVAF = 7.22, df 1, p = 0.010). One month of melatonin treatment did not influence other sleep parameters, pain, quality of life, cognitive processing speed and vigilance.

Conclusions

In chronic whiplash syndrome patients with delayed melatonin onset, 4 weeks’ treatment with melatonin 5mg, administered 5 hours before endogenous melatonin onset, advances melatonin onset and sleep-wake rhythm.

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Acknowledgements

We thank S.R. Pandi-Perumal, UCLA School of Medicine, Los Angeles, USA, for helpful discussions and critically reading the manuscript. This study was financially supported by the Matty Brand Foundation.

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Authors and Affiliations

  1. Department of Neurology and Sleep-Wake Disorders, Hospital Gelderse Vallei, Box 9025, Ede, 6710 HN, The Netherlands

    S. van Wieringen, T. Jansen &  M. G. Smits

  2. Department of Clinical Pharmacy, Hospital Eemland, Amersfoort, The Netherlands

    J. E. Nagtegaal

  3. NICI, Department of Psychology, University of Nijmegen, Nijmegen, The Netherlands

    A. M. L. Coenen

Authors
  1. S. van Wieringen
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  2. T. Jansen
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  3. M. G. Smits
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  4. J. E. Nagtegaal
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  5. A. M. L. Coenen
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Corresponding author

Correspondence to M. G. Smits.

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van Wieringen, S., Jansen, T., Smits, M.G. et al. Melatonin for Chronic Whiplash Syndrome with Delayed Melatonin Onset. Clin. Drug Investig. 21, 813–820 (2001). https://doi.org/10.2165/00044011-200121120-00003

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  • DOI: https://doi.org/10.2165/00044011-200121120-00003

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