Medical Perspectives | Others

June 06, 2020



Marie Angela M. Gochangco, M.D.

In our fast-paced world today, having adequate sleep is often neglected. Sleep is essential for health and well-being. Adults need 7 to 9 hours of sleep everyday.1 Getting quality sleep is also essential to promote good metabolic function and normal weight, to boost the immune system, and to prevent chronic conditions such as cardiovascular disease, diabetes, obesity, and depression.

 

Statistics in the Philippines

 

            The Philippines has one of the highest rates of sleep deprivation in the world. More than 10 million adults suffer from insomnia.14 According to the 2016 Healthy Living Index Survey, 46 percent of Filipinos do not get enough sleep, with 32 percent sleeping only for less than six hours.15

 

What is Insomnia?

 

According to the World Health Organization, insomnia is the inability to obtain sleep. It includes difficulty in falling asleep, frequent nocturnal awakening, and early morning awakening.2 Insomnia negatively affects work performance, impairs decision-making, and promotes a bad lifestyle. It remains to be a problem for the general population.

 

The diagnostic criteria for primary insomnia on adults from the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) include: (1) difficulty initiating sleep, (2) difficulty maintaining sleep, characterized by frequent awakenings or problems returning to sleep after awakenings, (3) early-morning awakening with inability to return to sleep, and (4) the sleep difficulty is present for at least 3 months.

 

The (DSM-V) criteria further states that the sleep disturbance causes clinically significant distress or impairment in social, occupational, educational, academic, behavioral, or other important areas of functioning.3

 

Causes of insomnia include physical and psychological factors. It can be commonly caused by electronic devices, disruptions in circadian rhythm (jet lag, job shift, and noisiness), stress, and psychological issues (depression, anxiety disorders).4

 

Medical conditions can also cause insomnia. These include brain lesions, stroke, chronic pain, Parkinson disease, Alzheimer disease, congestive heart failure, acid reflux disease, sleep apnea, asthma, arthritis, and nasal allergies. Withdrawal to medications such as sedatives and analgesics may also cause insomnia4.

 

The Cure for Insomnia

 

The latest guidelines from the European Sleep Research Society and the American Academy of Sleep Medicine are based from systematic reviews and relevant meta-analyses and concluded that cognitive behavioral therapy should be the first line therapy offered to patients. Cognitive behavioral therapy comprises of psychoeducation about sleep and sleep hygiene, sleep restriction therapy, stimulus control therapy, and relaxation training.5

 

Pharmacological treatments for primary sleep disorders include benzodiazepines, sedating antidepressants, and other drugs with sedating properties like anxiolytics, antipsychotics, and antihistamines. Side-effects can range from residual daytime sleepiness to dependence.6

 

The “z-drugs” such as eszopiclone, zolpidem, and zaleplon are benzodiazepines and are generally believed to be better and safer. The most common adverse effects of z-drugs include headache, gastrointestinal upset, and dizziness. Tolerance, dependence, and withdrawal are all reported with z-drugs, though this appears to be less severe and with lower incidence than for traditional benzodiazepines in the treatment of insomnia.7

           

Natural remedies as sleep-aid agents

 

            Medicinal plants have been the subjects of many clinical researches. They are traditionally known to have anxiolytic properties and are believed to have minimal unwanted side effects hence are preferred for the treatment of acute insomnia.

 

            The study of Hu, Z., et al. in 2018 discussed various natural products studied in their laboratory. These natural products have been shown to have sedative properties. Among these are magnolia, Semen zizyphi spinosae, simomenine, decursinol, rosemary, Euphoria longan, Ginseng, EGCG (Epigallocatechin-3-O-gallate, Camellia sinensis), Chrysanthemum morifolium, and Apigenin. The sedative property is primarily mediated through the activation of GABAA receptors which promotes sleep and relaxation.8

           

The mechanisms of herbal insomnia medications that target GABAergic systems include: (1) modifying GABAA receptors, the most common sites of action of the discussed herbal medications, as shown for kava-kava; (2) increasing GABA synthesis, as shown for Zizyphus jujuba; and (3) influencing GABA release, such as Ternstroemia lineate.9

 

Melatonin is a hormone produced by the pineal gland and is involved in the regulation of the circadian rhythm. It has been used for almost two decades for the treatment of sleep disorders. Exogenous supplementation of melatonin is well tolerated and has no apparent short or long-term adverse effects.10

The meta-analysis done by Ferracioli-Oda, E., et al in 2013 demonstrated that melatonin decreases sleep onset latency, increases total sleep time, and improves overall quality of sleep.6 It has minimal dependence and abuse potential. The benign side effect profile of melatonin makes it a favorable sleeping aid in insomnia.

 

Improve sleep with Seditol

           

            A promising agent in sleep-aid is Seditol. Seditol is a proprietary blend of a patented extract of Magnolia bark and Ziziphus spinosa seed. It is comprised of a minimum of 2.7% honokiol, an active constituent of Magnolia officinalis bark and 0.1% spinosin, a chemical marker of quality for Ziziphus spinosa seeds.11

 

            Magnolia has been traditionally used for the treatment of thrombotic stroke, depression, anxiety and neuronal diseases. Compounds isolated from Magnolia that have anxiolytic and sedative properties include magnolol, honokiol and obovatol. These compounds are positive allosteric modulators of GABAA receptors, hence promoting an increase in GABA activity and subsequent relaxation and sedation.8

            Zizyphus jujube has been used as an anxiolytic and as a treatment for insomnia and anxiety. Spinosin is the flavonoid glycoside extracted from Ziziphus jujube. Spinosin improves pentobarbital-induced sleep significantly, as reflected by increased sleep time and reduced sleep latency. The mechanism of action of spinosin involves binding with the post-synaptic serotonin receptor 5HT1A, consequently promoting sleep.12

           

Interactions of seditol with adenosine A1 receptor, dopamine transporter ,and dopamine D5 receptor (antagonist activity), serotonin receptors 5HT1B and 5HT6 (antagonist activity), and the GABA benzodiazepine receptor at 100 mcg/mL or lower were demonstrated.11 The results in the receptor binding models are consistent with the traditional uses of the extracts of Magnolia bark and Ziziphus spinosa seed as anxiolytic agents.

 

Seditol was well tolerated in an open label study in 295 volunteers. Beneficial effects were observed among 80% of participants with mild to moderate sleep difficulties. The most commonly reported mild complaint among 2.7% of the participants was a feeling of being dazed or groggy in the morning. No significant adverse events were reported. The product was shown to be relaxing, assisting in a restful sleep and effective in reducing fatigue due to lack of sleep.13

 

A wide variety of natural products can be used to promote sleep and relaxation. These agents are generally tolerated with lesser side effects compared with pharmacological treatments (benzodiazepines, sedating antidepressants, antidepressants, antihistamines). Future preclinical and clinical studies should be carried out to further determine the effects of these natural products in the treatment of insomnia.

 

 

References:

  • Hirshkowitz, M. et al. National Sleep Foundation’s sleep time duration recommendations: methodology and results summary. Journal of National Sleep Foundation. 2015.
  • Riba, F. (1993).  Insomnia Behavioural and Cognitive Interventions. World Health Organization. Retrieved from: https://apps.who.int/iris/bitstream/handle/10665/58229/WHO_MNH_PSF_93.2H.pdf;jsessionid=BC6FCB361E216E43ADCC188375F8FB3C?sequence=1.
  • Impact of the DSM-IV to DSM-5 Changes on the National Survey on Drug Use and Health. (2016). Retrieved from https://www.ncbi.nlm.nih.gov/b...
  • Singh, P. Insomnia: A sleep disorder: Its causes, symptoms and treatments. International Journal of Medical and Health Research. 2016.
  • Anderson, K. Insomnia and cognitive behavioural therapy- how to assess your patient and why it should be a standard part of care. Journal of Thoracic Disease. 2018.
  • Ferracioli-Oda. E., et al. Meta-Analysis: Melatonin for the Treatment of Primary Sleep Disorders. PLOS One. 2013.
  • Gunja, N. The Clinical and Forensic Toxicology of Z-drugs. Journal of Medical Toxicology. 2013.
  • Hu, Z., et al. Sleep-Aids Derived from Natural Products. Biomolecules and Therapeutics. 2018.
  • Shi, Y., et al. Herbal Insomnia Medications that Target GABAergic Systems: A Review of the Psychopharmacological Evidence. Current Neuropharmacology. 2014.
  • Xie, Z., et al. A review of sleep disorders and melatonin. Neurological Research. 2017.
  • Koetter, U., et al. Interactions of Magnolia and Ziziphus extracts with selected central nervous system receptors. Journal of Ethnopharmacology. 2009.
  • Wang, L., et al. Potentiating effect of spinosin, a C-glycoside flavonoid of Semen Ziziphi spinosae on pentobarbital-induced sleep may be related to postsynaptic 5-HT(1A) receptors. 2010.
  • LaValle, J., et al.A proprietary blend of Magnolia and Ziziphus extracts assists with sleep: an open-label assessment.
  • St. Luke’s launches first ever Comprehensive Insomnia Management Program in PH. (2019). Retrieved from https://www.stlukes.com.ph/new...
  • 46% of Filipinos Don’t Get Enough Sleep. (2017). Retrieved from https://www.pressreader.com/

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