Melatonin treatment in patients with cfs

Journal: J of Chronic Fatigue Syndrome, Vol. 11(3) 2003 pp. 69-72

Author: Jo Nijs, MSc

Affiliation: Jo Nijs is affiliated with the Department of Human Physiology,
Faculty of Physical Education and Physical Therapy, Vrije Universiteit
Brussel (VUB), Belgium, and the Institute for Occupational and Physical
Therapy, Department of Health Care, Hogeschool Antwerpen, Belgium.



THERAPY OF CIRCADIAN RHYTHM DISORDERS IN CHRONIC FATIGUE SYNDROME: NO
SYMPTOMATIC IMPROVEMENT WITH MELATONIN OR PHOTOTHERAPY. Williams G,
Waterhouse J, Mugarza J, Minors D, Hayden K. European Journal of Clinical
Investigation 2002;32:831-837.

The primary aim of this study (1) was to examine the effectiveness of
melatonin and bright-light phototherapy, both of which are capable of
adjusting circadian rhythms in healthy subjects, in improving the symptoms
and quality of life in patients fulfilling the Oxford criteria (2) for
Chronic Fatigue Syndrome (CFS). The same group previously revealed that the
peak of the circadian temperature rhythm and the onset of melatonin
secretion do not correlate in patients with CFS, while a significant
association was observed in healthy controls (3). This observation,
confirmed by the data presented in the new study (1), provided part of the
rationale for this trial. Melatonin is involved in synchronizing circadian
systems. A total of 42 CFS patients participated in the trial; all of them
received placebo capsules during the initial 12-week period. Afterwards,
they were randomized to receive either 5 mg melatonin capsules or home
phototherapy (1 hour each morning) for a duration of 12 weeks. At the start
of the 25th week, all subjects entered a 12-week washout period (placebo
capsules). Finally, the study participants switched treatments (those who
had received phototherapy were now given melatonin and vice versa-crossover
design), followed by a final 12week washout period. Both treatments were
well tolerated, but neither was able to modify symptom presentation or
quality of life compared to the placebo treatment. Likewise, neither
melatonin treatment nor phototherapy was able to alter the body temperature
rhythm or the onset of melatonin secretion in CFS patients. Although
unaffected by melatonin, the acrophase of the temperature rhythm was
significantly advanced by phototherapy (p = 0.04).

These results are in accordance with the data presented by van de Luit et
al. (4), who concluded from a 4-week open-label study of four CFS patients,
that melatonin may not be beneficial for altering circadian rhythm
disorders in patients with CFS. This same study revealed that patients with
CFS are characterized by increased amplitudes of circadian rhythms and
systolic blood pressures consistently below 100 mmHg during the nighttime
(4). Furthermore, from their studies of nocturnal melatonin levels in
CDCP-defined CFS patients, both Korszun et al. (5) and Knook et al. (6)
concluded that there is no rationale for melatonin supplementation in
patients with CFS.

The trial is well designed; still some trial weaknesses were identified:
the randomization procedure was not described; the smallest groups after
randomization lacked strength; and the dropout rate was high (12/42 or
28.6%). The authors did not address the topic of co-interventions (were
they prevented or standardized?). It could not be extracted from the data
presented in the manuscript whether an intention-to-treat analysis was
performed. Apart from the 12-week washout period at the end of the trial,
no follow-up period was included. Although the authors did not discuss the
reliability and validity of the outcomes measures, validated measurement
tools were used in the trial. For instance, visual analogue scales for
pain, fatigue, sleep disturbances, etc., were used. The pain scores
obtained with the V AS are believed to be reliable (7,8) and sensitive (9).
Furthermore, the psychometric properties of the Medical Outcomes Short Form
36 Health Status Survey (MOS SF-36) are well
characterized; it has been documented to have reliability and validity in a
wide variety of patient populations (10,11). The diagnosis of CFS was
established using the Oxford criteria (2). Compared to the 1994 CDCP
(Centre for Disease Control and Prevention) case definition for CFS (12),
Sharpe et al. (2) describe a much broader definition of CFS. British CFS
researchers have chosen not to include symptoms of depressive illness and
anxiety disorders as exclusion factors, for they consider these symptoms to
be central and debilitating aspects of the syndrome (2). Additionally,
fewer symptom criteria are used for it has been argued that no symptoms
have been shown to be specific for CFS (13). Consequently, extrapolation of
research results addressing Oxford defined CFS patients to Fukuda et aI.
defined subjects may be inappropriate.

In conclusion,
--------------------
this study points to the need of studying circadian rhythm
disorders in patients with CFS. The use of melatonin treatment has become
widespread in patients with CFS. The lack of effectiveness of melatonin and
phototherapy, either alone or in combination, in modifying symptoms,
quality of life, and circadian rhythm disorders should consequently guide
health care workers in the management of CFS.

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