More ZZZ’s for Those Who Wheeze

Abstract & Commentary

Synopsis: Melatonin improved subjective sleep quality in women with mild asthma.

Source: Campos FL, et al. Am J Respir Crit Care Med. 2004;170:947-951.

This was a blinded, randomized, placebo controlled study of 22 young women with mild-to-moderate asthma. Those who smoked, had frequent asthma exacerbations, used sleeping pills, or had other significant confounding problems (including smoking) were excluded. Subjects underwent a 2-week stabilization and washout period, during which everyone took inhaled steroids. Beta agonists were used prn. At the end of the baseline stabilization period, baseline data, including the Pittsburgh Sleep Quality Index (PSQI),1 the Epworth Sleepiness Scale,2 and pulmonary function were measured. Then subjects took either 3 mg of melatonin or 3 mg placebo 2 hours before bedtime for 28 days. They recorded their morning and evening peak flows (PEFR), asthma symptoms, and use of rescue beta agonists every day. Measurement of PSQI, Epworth Sleepiness Score, and pulmonary function were repeated at the end of the study period.

Twelve women received melatonin and 10 got placebo, but one of the melatonin subjects was lost to follow-up. At baseline, subjects were not different with regard to baseline measures, and 8 patients in each group were characterized as "poor sleepers," based on PSQI scores of 6 or more.

After 28 days, the group that received melatonin had a significant (P < 0.001) improvement in PSQI scores (from 7.4 to 3.4), but those who got placebo had no improvement. There was a trend (P =0.05) toward improved daytime sleepiness in the melatonin group.

Spirometry did not change significantly, but PEFR’s improved significantly for both groups. Adverse effects were minimal; 8 patients (5 from the melatonin group) had headaches, and one from the placebo group had epigastric pain.

Comment by Barbara A. Phillips, MD, MSPH

The fact that this smallish study of subjective sleep quality was published in a premier pulmonary journal speaks volumes about the perceived importance of sleep disturbance in patients with lung disease. Sleep complaints are common among pulmonary patients, and this is particularly true of asthmatics.3,4 Further, impaired sleep may adversely affect daytime function quality of life in asthmatics.4 The statistically robust finding of improved subjective sleep compared with placebo in this small group of asthmatic women suggests that the relationship is real. Since asthma and its associated morbidity, including sleep disturbance, are prevalent, there are patients in most of our practices who are potential candidates for this treatment.

But first let’s remember that melatonin is not FDA-approved or regulated. Those of use who lived through the tryptophan eosinophilic myalgia debacle5 are loath to experience anything like it again! A careful review of the findings of this study and their potential applications is in order. First and foremost, asthmatic patients who are considering melatonin for improvement in sleep quality need to be advised that the drug is not FDA approved; for medico-legal purposes, it is probably wise to document the warning in the medical record.

The biologic rationale for the use of melatonin in asthma is that it may modulate immune function,6 and help regulate smooth airway tone.7 In this study, however, there was no difference in measured pulmonary function, respiratory symptoms, or peak flows between the placebo and the treatment groups. Both groups experienced modest improvement in PEFR, probably the result of the Hawthorne effect. Thus, melatonin should not be given with the expectation that it will improve asthma. 

The patients studied in this report were relatively young women who did not have co-morbid psychiatric or medical illness. Women appear to experience a marked increase in melatonin availability compared with men.8 Thus, it is probably not reasonable to extrapolate these data to men, to older women, or to patients who have psychiatric or medical conditions contributing to their insomnia. In truth, patients with insomnia who do not have underlying medical or psychiatric issues are the exception rather than the rule.9

The dose used here was 3 mg, which is probably industrial strength. There is no justification or rationale for using higher doses. Further, timing of melatonin administration is key; in this experiment, it was given 2 hours before bedtime.

With those caveats, it might be reasonable to undertake a month’s trial of 3 mg of melatonin, 2 hours before bedtime, in young, relatively healthy women with mild asthma who understand that it is not FDA approved and will most likely not improve their asthma. The time has probably come to pay as much attention to sleep problems as to pain in addressing quality of life.

Dr. Phillips, Professor of Medicine, University of Kentucky; Director, Sleep Disorders Center, Samaritan Hospital, Lexington, KY, is Associate Editor of Internal Medicine Alert.

References

1. Buysse DJ, et al. Psychiatry Res. 1989;28:193-213.

2. Johns MW. Sleep. 1991;14:540-545.

3. Janson C, et al. Eur Respir J. 1996;9:2132-2138.

4. Fitzpatrick MF, et al. Thorax. 1991;46:569-573.

5. Hibbs JR, et al. Arthritis Rheum. 1992;35:299-303.

6. Reiter RJ, et al. Ann NY Acad Sci. 2000;917: 376-386.

7. Bruderman I, Rahaminoff R. J Appl Physiol. 1967;23: 938-943.

8. Fourtillan JB, et al. Biopharm Drug Dispos. 2000;21: 5-22.

9. Buysse DJ, et al. Sleep. 1994;17:630-637.