Kurdi, M.S., & Muthukalai, S.P. (2016). The efficacy of oral melatonin in improving sleep in cancer patients with insomnia: A randomized double-blind placebo-controlled study. Indian Journal of Palliative Care, 22, 295–300. 

To conduct a randomized, double-blind, placebo-controlled efficacy study evaluating the effects of oral melatonin in improving sleep in patients with cancer experiencing symptoms of insomnia

The investigators randomized participants who consented into group A (melatonin) or group B (placebo) using a fishbowl technique. Melatonin (3 mg) or placebo (multivitamin tablet) was provided by a pharmacist. Tablets were similar in color (light yellow) and shape, and were wrapped in similar envelopes and given to participants. Instructions were to take tablets two hours prior to bedtime every day for 14 days. The Athens Insomnia Scale (AIS) was given by phone or in person on days 1, 7, and 14. Patients and evaluators were blinded to the drug group, and the group was revealed to research staff at the end of the study. Results were compared using a paired t test.

• N = 50    
• MALES: 13% (group A), 13% (group B); FEMALES: 12% (group A),12% (group B)
• CURRENT TREATMENT: Other
• KEY DISEASE CHARACTERISTICS: Any patients with cancer with sleep complaints were included. No specific exclusion criteria were noted.

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: India

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Palliative care

Prospective, randomized, double-blind, placebo-controlled study

The AIS self-assessment psychometric tool for measurement of sleep difficulty is an eight-item scale, and the first five items assess sleep induction, nighttime awakenings, final awakening, total sleep duration, and sleep quality. The remaining three items assess daytime well-being, functional capacity, and sleepiness. Items are scaled using 0–3 ratings, from 0 (no problem) to 3 (no sleep at all). The scale cut-off is 10 to predict outcomes.

Power for a sample size of 25 was verified (90% and alpha = 5%). No significant differences in demographic characteristics of age and sex existed (p > 0.05). Each group had one dropout. The sample was predominantly stage 1 (44% [group A], 40% [group B]) and stage 2 (32% [group A], 36% [group B]), and stage 3–4 was 24% in each group. The majority of subjects (54%) had head and neck cancer (e.g., tongue, larynx) followed by cervix cancer (12%), and 14% had ovarian, gastrointestinal, breast, and sarcomas. Group A had significantly improvements in sleep (p < 0.05) on the AIS at week 1 with intragroup improvements in group A in week 2 (p = 0.00001). The percent change in sleep improvement within group A was significant (p = 0.0001) but not significant in group B (p > 0.05).

The use of 3 mg of melatonin two hours prior to bedtime is an effective nonpharmacological treatment for increasing sleep induction and sleep quality in patients with cancer experiencing insomnia.

• Small sample (< 100)
• Measurement validity/reliability questionable
• Questionable protocol fidelity

Additional large-scale randomized studies are needed to determine efficacy. Melatonin has emerging data to support the nonpharmacological treatment of sleep problems in patients with cancer.