Lasting treatment effects in a postmarketing surveillance study of prolonged-release melatonin - PubMed (original) (raw)

Lasting treatment effects in a postmarketing surveillance study of prolonged-release melatonin

Göran Hajak et al. Int Clin Psychopharmacol. 2015 Jan.

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Abstract

Surveillance studies are useful to evaluate how a new medicinal product performs in everyday treatment and how the patient who takes it feels and functions, thereby determining the benefit/risk ratio of the drug under real-life conditions. Prolonged-release melatonin (PRM; Circadin) was approved in Europe for the management of primary insomnia patients age 55 years or older suffering from poor quality of sleep. With traditional hypnotics (e.g. benzodiazepine-receptor agonists), there are concerns about rebound insomnia and/or withdrawal symptoms. We report data from a postmarketing surveillance study in Germany on the effects of 3 weeks of treatment with PRM on sleep in patients with insomnia during treatment and at early (1-2 days) and late (around 2 weeks) withdrawal. In total, 653 patients (597 evaluable) were recruited at 204 sites (mean age 62.7 years, 68% previously treated with hypnotics, 65% women). With PRM treatment, the mean sleep quality (on a scale of 1-5 on which 1 is very good and 5 is very bad) improved from 4.2 to 2.6 and morning alertness improved from 4.0 to 2.5. The improvements persisted over the post-treatment observation period. Rebound insomnia, defined as a one-point deterioration in sleep quality below baseline values, was found in 3.2% (early withdrawal) and 2.0% (late withdrawal). Most of the patients (77%) who used traditional hypnotics before PRM treatment had stopped using them and only 5.6% of naive patients started such drugs after PRM discontinuation. PRM was well tolerated during treatment and the most frequently reported adverse events were nausea (10 patients, 1.5%), dizziness, restlessness and headache (five patients each, <1%). There were no serious adverse events and no adverse events were reported after discontinuation. The persisting treatment effect and very low rebound rate suggest a beneficial role of sleep-wake cycle stabilization with PRM in the treatment of insomnia.

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Figures

Fig. 1

Fig. 1

Study design.

Fig. 2

Fig. 2

Overall study patients’ disposition. APTS, all-patients-treated set; FAS, full-analysis set; PPS, per-protocol set; SmPC, summary of product characteristics.

Fig. 3

Fig. 3

Sleep quality and morning alertness: (a) percentage of patients with very good, good, fair, bad, and very bad sleep quality at baseline, during treatment, at immediate, and at late withdrawal. (b) Percentage of patients who felt completely alert, alert, fair, tired, and very tired at baseline, during treatment, at immediate, and at late withdrawal.

Fig. 4

Fig. 4

Rebound insomnia: percentage of patients with a deterioration by at least one point from baseline at immediate and late withdrawal in sleep quality or morning alertness. As a comparison, the percentage of patients deteriorating during ongoing treatment is also shown.

Fig. 5

Fig. 5

Use of benzodiazepine and benzodiazepine-like hypnotics: number of patients who used traditional hypnotics before, during the course of, and after prolonged-release melatonin treatment. Percentage of patients using traditional hypnotics (out of 597 in the study) is also shown.

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