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Clinical Update on Insomnia

Updated: Feb 29


sleepy woman

This post discusses our insomnia epidemic, evidence-based behavioral interventions for insomnia, biofeedback and neurofeedback efficacy, a limited role for prescription drugs and supplements, and current evidence concerning non-prescription drugs.

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Jane






Our Insomnia Epidemic

About 10% of people experience chronic insomnia, which can manifest itself as difficulty falling asleep, difficulty staying asleep, waking up too early, or waking in the morning without feeling refreshed. And roughly 50% of people with other medical or psychological conditions also complain of insomnia. Consequences of insomnia include daytime fatigue, lack of energy, poor concentration and memory, moodiness and irritability, and difficulty completing tasks (Julien, Advokat, & Comaty, 2023, p. 408).


Evidence-Based Behavioral Interventions


Good sleep hygiene should be the foundation for the treatment of chronic insomnia. We encourage you to review evidence-based practices in our Neuroscience Breakthroughs Since Graduate School - Part 1 Sleep.

Sleep post


An accredited sleep lab assessment should be considered when insomnia does not respond to behavioral interventions or a medical disorder is suspected (Harvard Medical School, 2019).


Behavioral interventions like cognitive behavioral therapy for insomnia (CBT-i) and biofeedback should be our first-line responses to chronic insomnia because they treat underlying causes, are effective during and after treatment, and rarely produce unwanted side effects.


In contrast, prescription and over-the-counter drugs do not treat underlying causes, provide no benefits after we stop taking them, can result in severe rebound insomnia after discontinuing them, and can produce mild-to-severe side effects (Harvard Medical School, 2019).


A systematic review of 20 randomized controlled trials involving over 1,100 chronic insomnia patients found that multimodal CBT-i reduced sleep latency by 20 minutes and increased total sleep time by 30 minutes compared to control patients (Trauer et al., 2015). These results were at least as good or superior to those achieved by prescription sleep medication but without their side effects. In one study, CBT-i was effective 6 months after therapy ended. Julien and colleagues (2023) observed: "Advantages of CBTs include lack of drug side effects, no dependence or withdrawal issues, and safety for use with pregnant women. However, CBTs can be expensive, have a delayed onset of effect, and may not be readily available" (p. 408).



Biofeedback and Neurofeedback Efficacy

Evidence-Based Practice

Diego A. Garcia (2023) rated biofeedback and neurofeedback for insomnia, level 3, probably efficacious, based on 12 randomized controlled trials. Biofeedback interventions included EMG and skin conductance. Neurofeedback included sensorimotor rhythm (SMR) and theta.




A Limited Role for Prescription Drugs and Supplements


The Food and Drug Administration (FDA) has approved sleep medications for the short-term (1-6 months) treatment of insomnia. Short-term challenges to sleep include family crises, travel across time zones, and pandemics.

Patients should start with the lowest effective dose and use them as briefly as possible (Harvard Medical School, 2019).



Minimal Benefits


The most effective prescription sleep drugs may extend sleep by 20-30 minutes. Several drugs (Rozerem and Belsomra) only increased total sleep time by 9 or 10 minutes (Sateia et al., 2017).


The American Academy of Sleep (Sateia et al., 2017) recommended against using Benadryl, melatonin, and valerian for sleep-onset or sleep-maintenance insomnia because evidence quality ranged from low to very low, and benefits equaled harm. In the case of L-tryptophan, evidence quality was high, and the harms outweighed the benefits.



Reduced Stage 3 Sleep


Benzodiazepines can suppress stage 3 sleep for several days after taking a dose. For example, Prosom (elprazolam) reduced stage 3 sleep from 4% to 1% in 35-year-old insomnia patients. Restoril (temazepam) reduced stage 3 sleep from 8% to 5% in 38-year-old patients (Roehrs & Roth, 2010).



Tolerance and Withdrawal


Tolerance, reduced drug effectiveness, can develop with extended use of sleep medication. Patients exceeding prescribed dosages to counter tolerance can experience physical dependence and potentially dangerous overdoses (Julien et al., 2023).


Withdrawal, which occurs when patients discontinue sleep drugs after months of use, can produce rebound effects in which anxiety and insomnia worsen. Physicians should supervise benzodiazepine withdrawal to prevent rare seizures (Harvard Medical School, 2019).



Drug Interactions


Benzodiazepines and non-benzodiazepines should not be used with CNS depressants like alcohol due to the risks of life-threatening respiratory depression and next-day sedation. Non-benzodiazepines like Ambien should also not be taken with antihistamines, muscle relaxants, and sedatives (Harvard Medical School, 2019). Plasma levels of tasimelteon increase sevenfold when co-administered with the SSRI fluvoxamine (Ogilvie et al., 2015).



Side Effects


Insomnia medication side effects include next-day drowsiness, less mental sharpness and impaired performance, memory gaps, dizziness, and unsteadiness. Benzodiazepines can worsen sleep apnea. Prescription drugs with longer elimination half-lives trade better sleep maintenance for next-day memory impairments and poor psychomotor performance (Boyle et al., 2008).


Premature Death


For patients taking non-benzodiazepines like Ambien (zolpidem) and Restoril (temazepam), fewer than 18 doses per year were associated with more than a three-fold increased risk of premature death not due to pre-existing risk factors (Kripke et al., 2012).



Dementia


A retrospective case-control study found that Ambien (zolpidem) was associated with increased dementia risk, with or without underlying disease, when confounding variables were controlled (Shih et al., 2015).


In the Health, Aging and Body Composition study (Leng, Stone, & Yaffe, 2023) involving about 3,000 older adults with an average age of 74, 20% developed dementia over an average follow-up of nine years. White participants who frequently used sleep medications had a 79% higher risk of developing dementia than those who rarely or never used such medications.


Sedating antihistamines like Benadryl can produce confusion (Carr, 2018) and have also been associated with an increased risk of dementia.


The long-term Adult Changes in Thought (ACT) prospective study conducted by the University of Washington and Group Health found that use of an anticholinergic like Benadryl for three or more years was linked to a 54% greater risk of dementia than taking the same dose for three or fewer months (Gray et al., 2015).



The Elderly

The elderly are more impaired by these drugs due to their slower metabolism. Since women clear these drugs more slowly than men, they may be more vulnerable to next-day sedation. A study of 4,669 community-dwelling individuals 65 and older using prescription sleep drugs revealed a 34% greater risk of falls over 2 years (Chen et al., 2017). Although massive Ambien overdoses have not resulted in fatalities, symptoms such as disorientation, accidents due to falling, memory impairments, and psychotic episodes have been observed in the elderly (Julien et al., 2023).


The American Geriatrics Society (AGS) advises against prescribing benzodiazepines for patients over 65 due to the risk of automotive accidents, delirium, falls, and fractures (2019 American Geriatrics Society Beers Criteria Update Expert Panel, 2019). Ambien is the prescription sleep medication most linked to parasomnias, including intricate sleep-induced behaviors like sleep driving. Wong et al. (2017) affirmed a significant association between Ambien and the onset of these unusual sleep-related activities.

Following Directions

Patients intensify side effects when they don’t follow directions regarding allowing at least 7 hours of sleep and not combining sleep drugs with CNS depressants and other medications. A Consumer Reports survey (Carr, 2018) found widespread violations of these guidelines.


One-in-10 survey respondents who used prescription sleep drugs reported using an opioid to sleep (Carr, 2018). Combining opioids with benzodiazepines or alcohol can produce fatal respiratory arrest.


In a study of almost 410,000 adults, patients prescribed sleep medication were nearly twice as likely to experience a car crash (Hansen et al., 2015).

Non-Prescription Drugs


Melatonin


Melatonin is sold over the counter for insomnia treatment but has limited effectiveness and a short half-life (Sateia et al., 2017). It may be more useful for individuals with irregular sleep-wake patterns, like shift workers and those experiencing jet lag (Sadeghniiat-Haghighi et al., 2016). Potential dangers exist when patients exceed the recommended 5 mg/day maximum dosage. Over-the-counter supplements may exceed this maximum by 478% (Li et al., 2022). Overdose symptoms can include confusion, dizziness, drowsiness, gastrointestinal distress, headache, hyperthermia, reproductive hormone imbalance, and worsened depression.



Cannabidiol


Cannabidiol (CBD) may have promise for treating insomnia when issues of purity, dose, route of administration, and timing are settled (Babson, Sottile, & Morabito, 2017). CBD may indirectly improve sleep by reducing anxiety and pain, which may disrupt sleep. CBD may directly promote sleep by acting at receptors that regulate sleep-wake cycles (Babson, Sottile, & Morabito, 2017).



THC


While THC may reduce sleep latency, it poses long-term risks of impairing sleep quality by reducing REM and Stage 3 sleep (mixed evidence; Babson, Sottile, & Morabito, 2017). THC may improve sleep for chronic pain patients, but chronic daily cannabis use may delay sleep onset, interfere with sleep maintenance, and cause next-day sedation (Conroy et al., 2016).



Quiz


Take a five-question quiz on Quiz Maker to assess your mastery.



Glossary


Ambien (zolpidem): a nonbenzodiazepine agonist at benzodiazepine receptors.


benadryl: an antihistamine medication, commonly known by its generic name diphenhydramine, used for treating allergic reactions, insomnia, and symptoms of the common cold. It acts by blocking histamine receptors and has sedative properties. benzodiazepines: a pharmacological group of sedative-hypnotic agents, with chlordiazepoxide (Librium) and diazepam (Valium) as examples. cannabidiol (CBD): a nonpsychedelic supplement derived from the genus Cannabis.


insomnia is a clinical condition characterized by difficulty falling asleep or maintaining sleep.


melatonin: a hormone secreted by the pineal gland, instrumental in regulating circadian cycles and exhibiting a daily production rhythm.


non-REM (NREM) sleep: a sleep phase lacking rapid eye movements, subdivided into stages 1, 2, and 3.


parasomnias: unplanned behaviors or experiences that occur during sleep, like driving, often indicating abnormal or partial arousal.


rapid eye movement (REM) sleep: a sleep stage identified by low-amplitude, high-frequency EEG waves, absence of muscle tone, and fast eye movements; alternatively termed paradoxical sleep.


sleep apnea: a sleep-related breathing disorder where periodic cessation or reduction of breath leads to frequent waking and resultant daytime sleepiness.


sleep-maintenance insomnia: a form of insomnia characterized by challenges in sustaining sleep through the night.


sleep-onset insomnia is a form of insomnia marked by difficulty initiating sleep at the beginning of the night.


slow-wave sleep (SWS): also known as stage 3 sleep or NREM 3, distinguished by the EEG display of high-amplitude delta waves.


stage 1 sleep: also termed NREM1; an initial phase of NREM sleep marked by low amplitude, irregular EEG patterns, a slowed heart rate, and relaxed muscle tone.


stage 2 sleep: also termed NREM2; a stage of NREM sleep defined by EEG bursts known as sleep spindles.


stage 3 sleep: also termed NREM3; characterized by the EEG presence of high-amplitude, low-frequency delta waves, indicating a state of deep sleep.


tetrahydrocannabinol (THC): the major psychoactive agent derived from the genus Cannabis.




References


Babson, K. A., Sottile, J., & Morabito, D. (2017). Cannabis, cannabinoids, and sleep: A review of the literature. Current Psychiatry Reports, 19(4), 23. https://doi.org/10.1007/s11920-017-0775-9 Boyle, J., Trick, L., Johnsen, S., Roach, J., & Rubens, R. (2008). Next-day cognition, psychomotor function, and driving-related skills following nighttime administration of eszopiclone. Human Psychopharmacology, 23(5), 385–397. https://doi.org/10.1002/hup.936

By the 2019 American Geriatrics Society Beers Criteria® Update Expert Panel (2019). American Geriatrics Society 2019 Updated AGS Beers Criteria® for Potentially Inappropriate Medication Use in Older Adults. Journal of the American Geriatrics Society, 67(4), 674–694. https://doi.org/10.1111/jgs.15767


Carr, T. (2018). The problem with sleeping pills: The benefits might be smaller, and the risks greater, than you expect. Consumer Reports. Chen, T. Y., Lee, S., & Buxton, O. M. (2017). A greater extent of insomnia symptoms and physician-recommended sleep medication use predict fall risk in community-dwelling older adults. Sleep, 40(11), 10.1093/sleep/zsx142. https://doi.org/10.1093/sleep/zsx142

Conroy, D. A., Kurth, M. E., Strong, D. R., Brower, K. J., & Stein, M. D. (2016). Marijuana use patterns and sleep among community-based young adults. Journal of Addictive Diseases, 35(2), 135–143. https://doi.org/10.1080/10550887.2015.1132986 Ebrahim, I. O., Shapiro, C. M., Williams, A. J., & Fenwick, P. B. (2013). Alcohol and sleep I: effects on normal sleep. Alcoholism, Clinical and Experimental Research, 37(4), 539–549. https://doi.org/10.1111/acer.12006 Gray, S. L., Anderson, M. L., Dublin, S., Hanlon, J. T., Hubbard, R., Walker, R., Yu, O., Crane, P. K., & Larson, E. B. (2015). Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Internal Medicine, 175(3), 401–407. https://doi.org/10.1001/jamainternmed.2014.7663 Hansen, R. N., Boudreau, D. M., Ebel, B. E., Grossman, D. C., & Sullivan, S. D. (2015). Sedative hypnotic medication use and the risk of motor vehicle crash. American Journal of Public Health, 105(8), e64–e69. https://doi.org/10.2105/AJPH.2015.302723

Harvard Health Publishing (2019). Improving sleep: A guide to a good night’s rest. A Harvard Medical School Special Health Report.

Julien, R. M., Advokat, C. D., & Comaty, J. E. (2023). Julien’s primer of drug action (15th ed.). MacMillan Learning.


Kripke, D. F., Garfinkel, L., Wingard, D. L., Klauber, M. R., & Marler, M. R. (2002). Mortality associated with sleep duration and insomnia. Archives of General Psychiatry, 59(2), 131–136. https://doi.org/10.1001/archpsyc.59.2.131 Kripke, D. F., Langer, R. D., & Kline, L. E. (2012). Hypnotics' association with mortality or cancer: A matched cohort study. BMJ Open, 2(1), e000850. https://doi.org/10.1136/bmjopen-2012-000850


Leng, Y., Stone, K. L., & Yaffe, K. (2023). Race differences in the association between sleep medication use and risk of dementia. Journal of Alzheimer's Disease, 91(3), 1133–1139. https://doi.org/10.3233/JAD-221006


Li, J., Somers, V. K., Xu, H., Lopez-Jimenez, F., & Covassin, N. (2022). Trends in use of melatonin supplements among US adults, 1999-2018. JAMA, 327(5), 483–485. https://doi.org/10.1001/jama.2021.23652 Ogilvie, B. W., Torres, R., Dressman, M. A., Kramer, W. G., & Baroldi, P. (2015). Clinical assessment of drug-drug interactions of tasimelteon, a novel dual melatonin receptor agonist. Journal of Clinical Pharmacology, 55(9), 1004–1011. https://doi.org/10.1002/jcph.507 Roehrs, T., & Roth, T. (2010). Drug-related sleep stage changes: Functional significance and clinical relevance. Sleep Medicine Clinics, 5(4), 559–570. https://doi.org/10.1016/j.jsmc.2010.08.002


Sadeghniiat-Haghighi, K., Bahrami, H., Aminian, O., Meysami, A., & Khajeh-Mehrizi, A. (2016). Melatonin therapy in shift workers with difficulty falling asleep: A randomized, double-blind, placebo-controlled crossover field study. Work, 55(1), 225–230. https://doi.org/10.3233/WOR-162376

Sateia, M. J., Buysse, D. J., Krystal, A. D., Neubauer, D. N., & Heald, J. L. (2017). Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: An American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med, 13(2), 307-349. https://doi.org/10.5664/jcsm.6470


Shih, H.-I,, Lin, C.-C., Tu, Y.-F., Chang, C.-M., Hsu, H.-C., Chi, C.-H., & Kao, C.-H. (2015).


Trauer, J. M., Qian, M. Y., Doyle, J. S., Rajaratnam, S. M., & Cunnington, D. (2015). Cognitive behavioral therapy for chronic insomnia: A systematic review and meta-analysis. Annals of Internal Medicine, 163(3), 191–204. https://doi.org/10.7326/M14-2841



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