Effects of prolonged‐release melatonin, zolpidem, and their combination on psychomotor functions, memory recall, and driving skills in healthy middle aged and elderly volunteers

Otmani, Sarah; Demazieres, Agnès; Staner, Corinne; Jacob, Nathalie; Nir, Tali; Zisapel, Nava; Staner, Luc

doi:10.1002/hup.980

Cited by 117 publications

(76 citation statements)

References 78 publications

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“…In addition, prolonged-release melatonin use is not associated with the residual effects which are often observed following administration of benzodiazepine and other allosteric modulators of the GABA A receptor. A study of the effects of prolonged-release melatonin in healthy men and women aged 55 years and over reported that prolonged-release melatonin was not associated with impaired memory recall, driving performance or psychomotor function (Otmani et al, 2008). Along these lines, prolonged-release melatonin has been recommended as a first line therapy in older insomnia patients (Wilson et al, 2010), and a large surveillance study recently reported that following withdrawal from Circadin®, sleep quality and alertness remained improved and rebound insomnia incidence was low for older insomnia patients (Hajak et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Randomised clinical trial of the effects of prolonged-release melatonin, temazepam and zolpidem on slow-wave activity during sleep in healthy people

2015

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Current pharmacological treatments for insomnia include benzodiazepine and non-benzodiazepine hypnotics targeting γ-aminobutyric acid (GABA) A receptors, as well as agonists of the melatonin receptors MT1 and MT2. Melatonin, temazepam and zolpidem are thought to exert their effect through different mechanisms of action, but whether this leads to differential effects on electroencephalogram (EEG) power spectra during sleep in middleaged people is currently not known. To establish whether the effects of prolonged-release melatonin (2 mg) on the nocturnal sleep EEG are different to those of temazepam (20 mg) and zolpidem (10 mg). Sixteen healthy men and women aged 55-64 years participated in a double-blind, placebocontrolled, four-way cross-over trial. Nocturnal sleep was assessed with polysomnography and spectral analysis of the EEG. The effects of single oral doses of prolonged-release melatonin, temazepam and zolpidem on EEG slow-wave activity (SWA, 0.75-4.5 Hz) and other frequencies during nocturnal non-rapid eye movement (NREM) sleep were compared. In an entire night analysis prolonged-release melatonin did not affect SWA, whereas temazepam and zolpidem significantly reduced SWA compared with placebo. Temazepam significantly reduced SWA compared with prolonged-release melatonin. Prolonged-release melatonin only reduced SWA during the first third of the night compared with placebo. These data show that the effects of prolonged-release melatonin on the nocturnal sleep EEG are minor and are different from those of temazepam and zolpidem; this is likely due to the different mechanisms of action of the medications.

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Section: Discussionmentioning

confidence: 99%

Randomised clinical trial of the effects of prolonged-release melatonin, temazepam and zolpidem on slow-wave activity during sleep in healthy people

2015

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“…Weeklong administration of zolpidem also did not signi fi cantly impair psychomotor or cognitive functioning [ 71 ] . In contrast, another study demonstrated that older subjects experience memory impairment the day following dosing with zolpidem [ 72 ] .…”

Section: Sedative-hypnotics and Anxiolyticsmentioning

confidence: 82%

“…It also appears to be an effective sleep aid in patients with dementia, reducing sleep latency and prolonging sleep duration, though long-term use may predispose to worsening affect [ 78 ] . In a randomized, crossover study comparing melatonin and zolpidem in healthy older individuals, a prolonged-release formulation of melatonin did not impact psychomotor functioning, memory, or driving skills, whereas zolpidem negatively affected all three measures [ 72 ] .…”

Section: Sedative-hypnotics and Anxiolyticsmentioning

confidence: 97%

Medications and Cognition in Older Adults

Caporaso¹

2012

Handbook on the Neuropsychology of Aging and Dementia

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The elderly patient is particularly susceptible to negative effects on cognition that can arise from certain medications. This may occur whether or not pre-existing cognitive impairment is present. Medications whose primary target is the central nervous system (e.g., antidepressants, antipsychotics, sedative-hypnotics) or those which are targeted at other primary systems (e.g., cardiovascular drugs, urinary anti-spasmodics) should be considered as contributing factors in the patient with confusion or memory decline. Steps that can be taken to reduce this risk include: coordination of medical care among the patient's clinicians to avoid polypharmacy, judicious selection of appropriate medications, use of the lowest effective drug dose, and substitution of non-pharmacologic therapies whenever possible. This chapter addresses potential complications of medication use in older adults with cognitive decline.

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“…Presently, nonbenzodiazepine, positive allosteric modulators of the GABA A receptor such as zolpidem (ZOL) are the most widely prescribed hypnotic medications. Although known to induce sleep, these compounds have been shown to significantly impair psychomotor and memory functions in rodents (Huang et al, 2010;Uslaner et al, 2013;Zanin et al, 2013), non-human primates (Makaron et al, 2013;Soto et al, 2013;Uslaner et al, 2013) and humans (Balkin et al, 1992;Wesensten et al, 1996Wesensten et al, , 2005Mattila et al, 1998;Mintzer and Griffiths, 1999;Verster et al, 2002;Storm et al, 2007;Otmani et al, 2008;Gunja, 2013). Such impairment can be particularly troubling when there is an urgent need for highly functional performance in the presence of drug such as with first responders, military personnel, and caregivers.…”

Section: Introductionmentioning

confidence: 99%

Effect of a Hypocretin/Orexin Antagonist on Neurocogniive Performance

Kilduff¹

2014

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information , 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE (DD-MM-YYYY)September 2014 (From -To) REPORT TYPE Annual DATES COVERED P ERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER SRI InternationalMenlo Park, CA 94025-3493 SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENT SUPPLEMENTARY NOTES ABSTRACTDuring Year 5, we continued tests of the hypothesis that disfacilitation of wake-promoting systems by the hypocretin (Hcrt) receptor antagonist almorexant (ALM) results in less functional impairment than the inhibition of neural activity produced by the benzodiazepine receptor agonist zolpidem (ZOL). One paper was published (Morairty et al. 2014), another has been accepted for publication (Dittrich et al., in press) and a third is in resubmission (Vazquez-DeRose et al., submitted). Data collection for Aims 2c and 3b.2 have been completed and data analysis ongoing; manuscripts will be written and submitted during Year 6. Data collection and analysis of Aim 3a is nearing completion; an abstract summarizing this work has been submitted for presentation at the 2014 Society for Neuroscience meeting. Data collection for Aims 3b.3, 4c and 6a have been initiated. The overall results obtained to date are consistent with the hypothesis that the hypocretin/orexin antagonist ALM produces less functional impairment than the benzodiazepine receptor agonist zolpidem (ZOL) because ZOL causes a general inhibition of neural activity whereas ALM specifically disfacilitates wake-promoting systems. SUBJECT TERMSSleep, performance, drug, neurotransmitter, hypocretin, orexin, benzodiazepine, zolpidem, neurochemistry, microdialysis INTRODUCTIONAlmorexant (ALM) is a hypocretin/orexin (Hcrt) receptor antagonist with a novel mechanism of action that has shown promise as an effective hypnotic. Preclinical data demonstrate that animals treated with ALM are easily aroused from sleep and are free of ataxia and other behavioral impairments. If this observation is confirmed in humans, it would have enormous implications for the management of disturbed sleep in both military a...

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Effects of prolonged‐release melatonin, zolpidem, and their combination on psychomotor functions, memory recall, and driving skills in healthy middle aged and elderly volunteers

Cited by 117 publications

References 78 publications

Randomised clinical trial of the effects of prolonged-release melatonin, temazepam and zolpidem on slow-wave activity during sleep in healthy people

Randomised clinical trial of the effects of prolonged-release melatonin, temazepam and zolpidem on slow-wave activity during sleep in healthy people

Medications and Cognition in Older Adults

Effect of a Hypocretin/Orexin Antagonist on Neurocogniive Performance

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