title: Lasting treatment effects in a postmarketing surveillance study of prolonged-release melatonin.
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.
authors: aDepartment of Psychiatry and Psychotherapy, University of Regensburg, Regensburg bDepartment of Psychiatry, Psychosomatic Medicine and Psychotherapy, Social Foundation Bamberg, Bamberg cLundbeck GmbH, Hamburg, Germany dNeurim Pharmaceuticals Ltd, Tel-Aviv, Israel eDepartment of Neurobiology Faculty of Life Sciences, Tel-Aviv University, Israel.
authors: Göran
authors: G
authors: Hajak
authors: Kathrin
authors: K
authors: Lemme
authors: Nava
authors: N
authors: Zisapel
mesh_terms: D000368:Aged; D003692:Delayed-Action Preparations; D005260:Female; D005858:Germany; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008550:Melatonin / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D061214:Patient Safety; D011358:Product Surveillance, Postmarketing; D011446:Prospective Studies; D012008:Recurrence; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D012890:Sleep / Q000187:drug effects*; D007319:Sleep Initiation and Maintenance Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors; D016896:Treatment Outcome; D014851:Wakefulness / Q000187:drug effects
chemical_list: D003692:Delayed-Action Preparations; D006993:Hypnotics and Sedatives; D008550:Melatonin