Sleep on the Spectrum
There are several cornerstones to health that are frequently overlooked by our modern healthcare system because they are dependent upon patient agency. Diet and Exercise are the two twin pillars that come to mind most frequently but equally important is your quality of sleep. Evolutionarily our sleep patterns have been regulated by the environmental factors of this world which were rather consistent for hundreds of thousands of years. The past century has dragged us violently into the future where our circadian rhythms are under a constant onslaught of artificial light, commercially available stimulants, and the otherwise general FOMO our 24/7 lifestyles create.
Since Pfizer has no vaccine for insomnia and brand name sleeping drugs are now off patent the constant marketing for these products has receded with the industry viewing it as an already tapped vein of resources. It is still an incredibly common complaint from patients, however. The initial symptoms of sleep deprivation are irritability, fatigue and difficulty focusing. As it progresses further it impairs communications, causes poor judgement, and stimulates an increase in the appetite. Ultimately this will lead to lethargy, apathy, and social withdrawal. It should come as no surprise that the symptoms of sleep deprivation mirror the troubles of our modern society so well.
Ethically studying sleep deprivation any further becomes an issue, but animal studies have confirmed that without sleep animals can and will die from a cascade of physiological failures. We do have some human trials though thanks to the work of the CIA who used tax dollars to incorporate sleep deprivation into their "enhanced interrogation techniques" which are now known by the more accurate but legally dubious term "torture". Perhaps it is the worst kind of torture since any information it produces should be immediately suspect due to the cognitive impairment of the subject.
If you step back and look at it many of the most common complaints faced by patients may have their root cause in a lack of sleep. It can be a difficult thing to diagnose since doctors tend to see patients while they are awake and the patient themselves being unconscious makes it a hard thing to measure. Many people are stuck relying on their significant other to inform them of their poor sleep, how many times a night have you been woken up with a pillow to the face? Single patients may struggle with vague symptoms and issues for an extended period or may never figure it out. Their sleep may even be negatively impacting their love life since snoring and other nighttime disruptions have been called "deal breakers" by those who provide relationship advice.
So many of us are torturing ourselves with a lack of sleep even if we don't realize it. Even if all else is well and our diet and exercise are what they should be, a lack of sleep can hurt any chance of improving your health. All sleep is not the same and the healthy restorative version that we need for our bodies to recover has become more and more elusive. Simply being unconscious is no replacement for proper rest.
Humans will chase sleep or self-medicate in a variety of ways. Depressants like alcohol will eventually render you unconscious if you consume enough. Antihistamines and other sedating over the counter medicines like diphenhydramine and doxylamine succinate are marketed for sleep under brand names like Unisom or ZZZquil but it’s essentially the same old Benadryl that has been around forever just in a different box (and much more expensive). The over-the-counter options for sleep are rather limited and can cause a hangover that lasts into the morning, a sure-fire sign that your sleep was not as restorative as it needs to be.
Supplements for improving sleep can be found everywhere, ranging from melatonin, CBD products, magnesium glycinate or herbal combinations like the “Sleep Perfect Formula” which includes almost everything that has ever been rumored to help with sleep (valerian root, GABA, L-Theanine, 5-HTP, chamomile, hops extract, passionflower, and the melatonin/magnesium for good measure). A tall glass of milk before bed has been a common suggestion to aid in sleep long enough to be called an old wives’ tale but studies have shown that impaired calcium homeostasis is linked to anxiety, insomnia and sleep disturbances. So, a tall glass full of liquid protein that has melatonin, calcium, and vitamin D is far from a bad idea.
Everything mentioned above may or may not improve your sleep but at least you won’t wake up with your car inside someone else’s living room. Using medication for sleep has always struck me as a risky proposition especially in an outpatient setting. Instead of addressing the underlying cause we attempt to ameliorate the symptoms with a prescription. While this may be necessary in some cases generalized overuse has caused its own set of problems. Nobody is interested in paying their office copay for just advice, so the prescription pad usually winds up getting involved.
The most benign options are antidepressants that have sedating properties like trazodone and mirtazapine. Since depression and difficulty sleeping usually come hand in hand these are appealing cost-effective drugs that can address both problems. Getting a little riskier benzodiazepines like diazepam became famous under the brand name Valium. The drug was so popular in the 70’s that it wound up as a punchline in the Burt Reynolds film Starting Over when the main character has a heart attack in a public place and his friend screams for a valium every lady in the store pulls a prescription bottle out of their purse. Hypnotic drugs like zaleplon, eszopiclone and zolpidem are the next tier up, but they come with dependency concerns and zolpidem has become notorious for side effects like sleep walking, sleep eating, sleep cooking to full on sleep driving and the most disturbing or awesome of all sleep sex. Memory impairment, abnormal thoughts and behaviors, hallucinations, and the very real risk of withdrawal make the safety profile something to be concerned about.
Michael Jackson is perhaps the best public example of how far someone will go to sleep and if you have unlimited resources just what that can get you. Our healthcare system is built around customer satisfaction, and he had the money to go all the way down the rabbit hole to a drug that has no place outside of a surgical setting, propofol. Michael had enough money to get access to this drug, but he didn’t know he also needed someone competent to administer it properly without killing him. Of course, anyone competent would likely respond with WTF are you doing. So, Michael was left with Dr. Write for anything drawing up his dose and then killing him. He may have even drawn up the proper dose, but the rate of administration is crucial when giving propofol and easy to mess up.
Goodnight and sleep tight, if you can!
Jacob Hyatt Pharm D.
Father of three, Husband, Pharmacist, Realtor, Landlord, Independent Health and Medicine Reporter
www.pharmacoconuts.com
@Hyattjn
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Further reading and references
https://www.psychologytoday.com/us/blog/dreaming-in-the-digital-age/201412/why-sleep-deprivation-is-torture
https://www.apa.org/monitor/2017/10/cover-sleep
https://pubmed.ncbi.nlm.nih.gov/28993837/
Wisden W, Yu X, Franks NP. GABA Receptors and the Pharmacology of Sleep. Handb Exp Pharmacol. 2019;253:279-304. doi: 10.1007/164_2017_56. PMID: 28993837.
https://pubmed.ncbi.nlm.nih.gov/37123350/
Boisgontier J, Beccaria K, Saitovitch A, Blauwblomme T, Guida L, Fillon L, Dufour C, Grill J, Lemaitre H, Puget S, Vinçon-Leite A, Dangouloff-Ros V, Charpy S, Benichi S, Levy R, Roux CJ, Grévent D, Bourgeois M, Saidoun L, Gaillard R, Zilbovicius M, Boddaert N. Case Report: Zolpidem's paradoxical restorative action: A case report of functional brain imaging. Front Neurosci. 2023 Apr 14;17:1127542. doi: 10.3389/fnins.2023.1127542. PMID: 37123350; PMCID: PMC10140395.
https://pubmed.ncbi.nlm.nih.gov/37069546/
Bonomo N, Huang H, Schoenbachler B. Rapid resolution of catatonia secondary to post traumatic stress disorder with secondary psychotic features through scheduled zolpidem tartrate. BMC Psychiatry. 2023 Apr 17;23(1):258. doi: 10.1186/s12888-023-04769-x. PMID: 37069546; PMCID: PMC10111647.
https://pubmed.ncbi.nlm.nih.gov/37047843/
Squitti R, Reale G, Tondolo V, Crescenti D, Bellini S, Moci M, Caliandro P, Padua L, Rongioletti M. Imbalance of Essential Metals in Traumatic Brain Injury and Its Possible Link with Disorders of Consciousness. Int J Mol Sci. 2023 Apr 6;24(7):6867. doi: 10.3390/ijms24076867. PMID: 37047843; PMCID: PMC10095508.
https://pubmed.ncbi.nlm.nih.gov/36749030/
Aquizerate A, Laforgue EJ, Istvan M, Rousselet M, Gerardin M, Jouanjus E, Libert F; French Addictovigilance Network; Guerlais M, Victorri-Vigneau C. French national addictovigilance follow-up of zolpidem between 2014 and 2020: evolution of drug abuse, misuse and dependence before and after the regulatory change. Eur J Public Health. 2023 Apr 1;33(2):169-175. doi: 10.1093/eurpub/ckad003. PMID: 36749030; PMCID: PMC10066475.
https://pubmed.ncbi.nlm.nih.gov/36901441/
Carbone EA, Menculini G, de Filippis R, D'Angelo M, De Fazio P, Tortorella A, Steardo L Jr. Sleep Disturbances in Generalized Anxiety Disorder: The Role of Calcium Homeostasis Imbalance. Int J Environ Res Public Health. 2023 Mar 1;20(5):4431. doi: 10.3390/ijerph20054431. PMID: 36901441; PMCID: PMC10002427.
https://pubmed.ncbi.nlm.nih.gov/36674498/
Dhillon VS, Deo P, Thomas P, Fenech M. Low Magnesium in Conjunction with High Homocysteine and Less Sleep Accelerates Telomere Attrition in Healthy Elderly Australian. Int J Mol Sci. 2023 Jan 4;24(2):982. doi: 10.3390/ijms24020982. PMID: 36674498; PMCID: PMC9866301.
https://pubmed.ncbi.nlm.nih.gov/32536366/
Ekholm B, Spulber S, Adler M. A randomized controlled study of weighted chain blankets for insomnia in psychiatric disorders. J Clin Sleep Med. 2020 Sep 15;16(9):1567-1577. doi: 10.5664/jcsm.8636. PMID: 32536366; PMCID: PMC7970589.
https://pubmed.ncbi.nlm.nih.gov/30248967/
Cao Y, Zhen S, Taylor AW, Appleton S, Atlantis E, Shi Z. Magnesium Intake and Sleep Disorder Symptoms: Findings from the Jiangsu Nutrition Study of Chinese Adults at Five-Year Follow-Up. Nutrients. 2018 Sep 21;10(10):1354. doi: 10.3390/nu10101354. PMID: 30248967; PMCID: PMC6212970.
https://pubmed.ncbi.nlm.nih.gov/35893875/
Jeon YS, Yu S, Kim C, Lee HJ, Yoon IY, Kim T. Lower Serum Calcium Levels Associated with Disrupted Sleep and Rest-Activity Rhythm in Shift Workers. Nutrients. 2022 Jul 22;14(15):3021. doi: 10.3390/nu14153021. PMID: 35893875; PMCID: PMC9331058.
https://pubmed.ncbi.nlm.nih.gov/22860241/
Dolder CR, Nelson MH, Iler CA. The effects of mirtazapine on sleep in patients with major depressive disorder. Ann Clin Psychiatry. 2012 Aug;24(3):215-24. PMID: 22860241.
https://pubmed.ncbi.nlm.nih.gov/36168907/
Li Y, Wu F, Mu Q, Xu K, Yang S, Wang P, Wu Y, Wu J, Wang W, Li H, Chen L, Wang F, Liu Y. Metal ions in cerebrospinal fluid: Associations with anxiety, depression, and insomnia among cigarette smokers. CNS Neurosci Ther. 2022 Dec;28(12):2141-2147. doi: 10.1111/cns.13955. Epub 2022 Sep 28. PMID: 36168907; PMCID: PMC9627395.
https://pubmed.ncbi.nlm.nih.gov/33186550/
Blum ID, Keleş MF, Baz ES, Han E, Park K, Luu S, Issa H, Brown M, Ho MCW, Tabuchi M, Liu S, Wu MN. Astroglial Calcium Signaling Encodes Sleep Need in Drosophila. Curr Biol. 2021 Jan 11;31(1):150-162.e7. doi: 10.1016/j.cub.2020.10.012. Epub 2020 Nov 12. PMID: 33186550; PMCID: PMC8442851.
https://pubmed.ncbi.nlm.nih.gov/30729219/
Parmalee NL, Aschner M. Metals and Circadian Rhythms. Adv Neurotoxicol. 2017;1:119-130. doi: 10.1016/bs.ant.2017.07.003. Epub 2017 Sep 1. PMID: 30729219; PMCID: PMC6361389.
https://pubmed.ncbi.nlm.nih.gov/29113075/
Cherasse Y, Urade Y. Dietary Zinc Acts as a Sleep Modulator. Int J Mol Sci. 2017 Nov 5;18(11):2334. doi: 10.3390/ijms18112334. PMID: 29113075; PMCID: PMC5713303.
