Insomnia

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Trazodone

  • Jaffer KY, Chang T, Vanle B, Dang J, Steiner AJ, Loera N, Abdelmesseh M, Danovitch I, Ishak WW. Trazodone for Insomnia: A Systematic Review. Innov Clin Neurosci. 2017 Aug 1;14(7-8):24-34. PMID: 29552421; PMCID: PMC5842888.
    • Has low rates of side effects with low doses used PRN for sleep.
  • Olanzapine and Quetiapine 2nd gen antipsychotics used for sleep and delirium. Avoid in older patients with dementia (black box warning).

Melatonin

Melatonin is a chronohypnotic that decreases firing rate of neurons in SCN via MT1 receptor, but only when endogenous levels are low (i.e. daytime). In older adults, the amount of MT synthesized and the number and affinity of MT1 receptors all decrease. Does not make you feel drowsy. It enhances natural sleep wake cycle. Must be paired with good sleep hygiene. Only need very small amounts (1 mg). Give 1 hr before bedtime. The body makes 1 mg per day, at higher doses exogenous melatonin might decrease your body's ability to synthesize it on its own. Higher doses in the short term show a dose dependent effect, but this wears off quickly and then melatonin stops working at all.

  • Zhdanova IV, Wurtman RJ, Regan MM, Taylor JA, Shi JP, Leclair OU. Melatonin treatment for age-related insomnia. J Clin Endocrinol Metab. 2001 Oct;86(10):4727-30. doi: 10.1210/jcem.86.10.7901. PMID: 11600532.
    • Double-blind, placebo-controlled study, subjects who slept normally (n = 15) or were insomniacs, i.e. exhibited actigraphically confirmed decreases in sleep efficiency (n = 15) received, in randomized order, a placebo and three melatonin doses (0.1, 0.3, and 3.0 mg) orally 30 min before bedtime for a week. There was a non-dose dependent increase in sleep efficiency in insomniacs but not in controls. The 3 mg dose caused transient hypothermia and supraphysiologic plasma melatonin levels that persisted for much of the following day.
  • Brzezinski A, Vangel MG, Wurtman RJ, Norrie G, Zhdanova I, Ben-Shushan A, Ford I. Effects of exogenous melatonin on sleep: a meta-analysis. Sleep Med Rev. 2005 Feb;9(1):41-50. doi: 10.1016/j.smrv.2004.06.004. PMID: 15649737.
    • In a meta analysis of 17 randomized, double-blind, placebo controlled studies with objective sleep eval including 284 patients, melatonin decreased sleep latency by 2-5 minutes, improved sleep efficiency by 2-3%, and increased sleep length by 13 min. Melatonin doses ranged from 0.1 to 80 mg PO, or 50 mg IV in one study.
  • Vural EM, van Munster BC, de Rooij SE. Optimal dosages for melatonin supplementation therapy in older adults: a systematic review of current literature. Drugs Aging. 2014 Jun;31(6):441-51. doi: 10.1007/s40266-014-0178-0. PMID: 24802882.
    • Meta analysis of 16 studies (9 RCTs), in older patients.
  • Fatemeh G, Sajjad M, Niloufar R, Neda S, Leila S, Khadijeh M. Effect of melatonin supplementation on sleep quality: a systematic review and meta-analysis of randomized controlled trials. J Neurol. 2022 Jan;269(1):205-216. doi: 10.1007/s00415-020-10381-w. Epub 2021 Jan 8. PMID: 33417003.
  • Duffy JF, Wang W, Ronda JM, Czeisler CA. High dose melatonin increases sleep duration during nighttime and daytime sleep episodes in older adults. J Pineal Res. 2022 Aug;73(1):e12801. doi: 10.1111/jpi.12801. Epub 2022 May 13. PMID: 35436355; PMCID: PMC9288519.
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