An Article reporting the results of phase II and III trials shows the drug tasimelteon to be effective for transient insomnia of the kind caused by night shift work and jet-lag. As such, this drug could be a first-line therapy for people burdened with the effects of travel across time zones or working at night. The Article, published Online first and in an upcoming edition of The Lancet, is written by Dr Shantha M.W. Rajaratnam and Dr Elizabeth B Klerman (Brigham and Women's Hospital, Harvard Medical School, Boston MA, USA; Monash University, Australia) and colleagues.
Circadian rhythm sleep disorders are common causes of insomnia that affect millions of individuals, including those who work at night or who cross multiple time zones during travel. These primary sleep disorders are characterised by persistent and recurrent sleep disturbances, insomnia when trying to sleep, and excessive sleepiness while trying to remain awake. They occur when scheduled or desired sleep times are not compatible with the body's circadian rhythms, eg, when a person has travelled across multiple time zones, or works night shifts.
The authors did phase II and phase III randomised, placebo-controlled, parallel-group studies to test efficacy of tasimelteon (a melatonin analogue) for treatment of transient insomnia associated with shifted-sleep and wake time. In the phase II study, 39 people from two US sites were randomly assigned to tasimelteon 10mg (9 people), 20mg (8), 50mg (7) or 100mg (7) or placebo (8). The subjects were monitored for seven nights: three at baseline, three after a 5-hour advance of sleep-wake schedule with treatment before sleep, and one after treatment. In the phase III study, 411 people from 19 US sites, who had transient insomnia induced in a sleep clinic by a 5-hour advance of the sleep-wake schedule and the first night spent in a sleep clinic, were given tasimelteon 20mg (100 people), 50mg (102), 100mg (106), or placebo (103) 30 minutes before bedtime.
Patients' sleep was assessed objectively by polysomnography (EEG, EOG and EMG) to determine the amount of sleep they obtained as a percentage of the time they spent in bed (ie, sleep efficiency) and the time it took for them to fall asleep (ie, sleep latency). The shift in the timing of the internal biological clock was assessed by measuring the plasma melatonin rhythm (phase II study). The researchers found that in both studies, when patients tried to sleep in a new time zone, tasimelteon reduced sleep latency and it improved sleep efficiency compared with placebo. The plasma melatonin rhythm was shifted earlier with tasimelteon compared with placebo. The frequency of adverse events was similar between the tasimelteon and placebo groups.
The authors say*: "The development of melatonin analogues, which specifically target melatonin receptors, will also help us to understand more about the role of the hormone melatonin in the regulation of sleep."
The authors conclude: "By simultaneously improving sleep latency and sleep maintenance with a shift in circadian rhythms, tasimelteon has the potential for the treatment of patients with transient insomnia associated with circadian rhythm sleep disorders, including people affected by jet lag, or those who work at night, and early-riser workers."
In an accompanying Comment, Dr Daniel P Cardinali, University of Buenos Aires, Argentina, and Dr Diego A Golombek, National University of Quilmes, Buenos Aires, Argentina, say: "Shift-workers, airline crew, tourists, football teams, and many others will welcome the results of Shantha Rajaratnam and colleagues' study in The Lancet today."
In their Comment, they discuss the advantages that melatonin analogues have over sleep therapies from the benzodiazepine family (eg diazepam/ valium), namely that benzodiazepines can cause addiction and dependence, whereas melatonin analogues do not.
Dr Shantha M.W. Rajaratnam and Dr Elizabeth B Klerman, Brigham and Women's Hospital, Harvard Medical School, Boston, USA can be contacted via Lori Shanks at The Brigham and Women's Hospital: T) +1-617-534-1604 or E) ljshanks@partners.org
Dr Daniel P Cardinali, University of Buenos Aires, Argentina contact by e-mail only E) dcardinali@fmed.uba.ar
Notes to editors: *quote direct from authors and not within text of Article
Full Artilce and Comment: http://press.thelancet.com/Tasimelteonfinal.pdf
Journal
The Lancet