Melatonin for chronic whiplash syndrome with delayed melatonin onset randomised, placebo-controlled trial

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 poly-somnography. Dim-light melatonin onset (DLMO) was measured in saliva. Qualify 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 5 mg, 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, poly-somnographic sleep architecture, cognitive processing speed and vigilance. Results: Mean (±SD) baseline DLMO occurred at 11.13 pm (±1:18h) in the melatonin treatment group and at 11.24 pm (±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 (AVOVA F = 6.68, df 1, p = 0.015). In the subgroup of chronic whiplash syndrome patients with melatonin onset between 10.30 pm and 1.00 am, melatonin also advanced diary lights-off time (ANOVA F = 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.