Fusion of Traditional and Contemporary Medicine in Treating Insomnia: An Exploration

INTRODUCTION

Insomnia is a disorder wherein patients tend to have frequent trouble falling or staying asleep, which leads to overall discontent with sleep despite having adequate opportunities for sleep. Additionally, the sleep problem is accompanied by anxiety over restless nights and/or impairment in a number of functional domains (such as defined by the American Academy of Sleep Medicine (AASM) (family, social, and vocational).¹ Over the course of medical classification development, insomnia has been defined in multiple ways: as a symptom of insomnia disorder. Categorization of insomnia as a symptom/indicator of an underlying psychiatric disorder to an independent disorder by itself is a challenge and debate on its own. One category for insomnia is short term if it lasts less than 3 months, and chronic if it lasts longer than 3 months and happens more than three times a week.¹

Despite recent advancements, our comprehension of insomnia’s nature, causes, and underlying mechanisms has been limited. It could be attributed to the diversity within insomnia, its high occurrence alongside other conditions, or variations in the analytical levels of models, ranging from observation to physiological study. Till now, there have been many theories about the pathophysiology. Let us explore some popular theories. In this review article, we also explore the mechanisms of sleep while considering various therapy modalities and their mechanisms of action. The evidence presented here is based on published literature and guidelines from various national and international organizations.^2,3

PHYSIOLOGICAL MECHANISMS OF SLEEP

Our brain’s inherent 24 hour clock, known as the circadian rhythm, controls our cycles of arousal and somnolence in reaction to variations in ambient light. This circadian rhythm helps us to adapt to environmental changes. Without it, neither we could have predicted the variations in radiation, temperature, and food availability nor have had the ability to maximize energy use and sustain internal physiological processes. The suprachiasmatic system (SCN) houses the biological clock that regulates sleep and awake. Suprachiasmatic system have an inbuilt circuit that results in circadian oscillations in neuronal activity. It also receives afferent fibers from the retina to regulate the cycle.^4,5 Melatonin, a hormone produced by the pineal gland, is regulated by the photoperiod and plays a crucial role in managing body rhythms, such as sleep and temperature. It is released during darkness and decreases during daylight. The pineal gland’s activity is governed by an internal rhythm generated by the SCN in the hypothalamus, with light having a dominant suppressive effect on this regulation. The pineal gland affects other biological processes by releasing melatonin into the bloodstream beats. In humans, melatonin promotes sleep and helps synchronize the sleep-wake cycle, making it effective in treating insomnia.^3,4

The Spielman model of insomnia, also known as the “Three-Factor” or “Three P” model, includes three components: predisposing, precipitating, and perpetuating factors. Predisposing factors are inherent traits that increase an individual’s vulnerability to insomnia, such as sleep reactivity, and personality characteristics like excessive worrying or rumination. Social factors, including mismatched sleep schedules between bed partners or societal pressures impacting sleep patterns, also play a role. The beginning of stressors is among the predisposing and triggering factors that frequently cause insomnia. Chronic insomnia can also persist due to behaviors like staying in bed later or earlier in an attempt to compensate for sleep deficits. These behaviors disrupt sleep homeostasis, causing insomnia to continue even after the initial trigger has been resolved or improved.²

Gamma-aminobutyric acid (GABA), a crucial inhibitory neurotransmitter, plays a central role in maintaining the balance between neuronal excitation and inhibition in the central nervous system and is essential for brain development and function. Approximately 20% of brain neurons are GABAergic. The regulation of sleep and arousal involves three types of GABA receptors: GABA_A, GABA_B, and GABA_C, although to varying degrees. Most commonly used hypnotics affect the GABA system, particularly by modulating the benzodiazepine site. Gamma-aminobutyric acid regulates the transition from rapid eye movement (REM) sleep to arousal or non-rapid eye movement (NREM) sleep by acting on REM-on and REM-off neurons in the brainstem and is considered the first line of treatment for insomnia. Additionally, numerous herbal medicines are believed to enhance GABAergic signaling, often by interacting with the GABA_A receptor.^2,5

Another major system involved in regulating sleep and wakefulness is the orexin neuropeptide signaling system. This system primarily maintains wakefulness throughout the day and plays a significant role in REM sleep. Derived from the precursor Pre-pro-orexin, two neuropeptides activate two post-synaptically localized G protein-coupled receptors, OX1R and OX2R. The start of REM sleep is suppressed by activating OX1R and OX2R, while non-REM sleep is likewise suppressed by activating OX2R. Thus, orexin agonists would promote arousal and antagonists would promote sleep. This mechanism has been used in the treatment of insomnia.^2,5

PRINCIPLES OF INSOMNIA THERAPY

Lack of sleep is detrimental to one’s physical and mental well-being. Insomnia is often characterized by heightened arousal, involving increased activity in both the central (cortical) and peripheral (autonomic) nervous systems. This heightened arousal can manifest as increased cognitive and emotional activity, potentially contributing to both short-term and long-term insomnia (Fig. 1). Despite its significance in the literature, hyperarousal is not consistently defined. In many studies, hyperarousal is described as heightened physiological, cognitive, and emotional activity that disrupts the natural disengagement from daily activities necessary for sleep.²

Treating insomnia involves various methods, from established medications to herbal remedies and newer adjunct therapies. In this discussion, we aim to thoroughly examine these treatment options, looking at how effective they are, how safe they are, and how they might work together to treat this widespread sleep disorder. By exploring each approach and observing how they affect sleep, we hope to shed light on the complexities of managing insomnia. Our goal is to discuss the integration of medication, herbal remedies, and other interventions, providing a fair assessment of how they can help people sleep better and improve their overall health.⁶

The primary recommendation for addressing insomnia, regardless of known causes, is cognitive behavioral therapy for insomnia (CBT-I) and other adjuvant therapies. Presently, there is no universal agreement on the most effective or balanced pharmacological approach. Cognitive behavioral therapy for insomnia and pharmacological methods are believed to produce comparable immediate results, yet only CBT-I has demonstrated sustained benefits even after treatment cessation. Combining CBT-I with medication may expedite treatment response but could compromise the lasting efficacy of CBT-I’s positive effects.^5,7–9

For centuries, plants or plant-derived materials have been utilized to provide therapeutic benefits for sleep disorders. Notable herbs include valerian, passionflower, lemon balm, and Californian poppy. Recent research has concentrated on analyzing the components of natural sleep aids and identifying the compounds responsible for their sedative effects. Various mechanisms of action have been proposed, including enhancing GABAergic signaling, often through interaction with GABA_A receptors. This therapy has been attempted for the treatment of insomnia, and herbal medicines have shown an exceptional safety record, particularly when compared to pharmacotherapy for insomnia. Additionally, they are widely accepted among patients.¹⁰

In ancient texts, sleep, known as Nidra, is recognized as one of the essential components for overall well-being. “Yoga Nidra,” a guided meditation technique, has gained attention in the last 20 years as a therapeutic approach for conditions like stress, mental health issues, and insomnia. It is distinct from traditional yoga as it doesn’t involve physical poses. Yoga Nidra offers a promising method to induce a deep state of relaxation akin to natural deep sleep, aiming for complete emotional, physical, and mental relaxation. Regular morning practice at home may alleviate anxiety and discomfort associated with waking up early, potentially enhancing sleep quality, quantity, and overall wellness. This non-pharmacological approach holds therapeutic promise for enhancing well-being.^10,11

PHARMACOTHERAPY FOR INSOMNIA

According to guidelines from the American Psychological Association (APA), it’s recommended to involve patients in decisions about using medication for insomnia. This involves discussing the benefits, risks, and costs of pharmacologic therapy. The American College of Physicians (ACP) treatment guidelines list pharmaceuticals that have been approved by the United States food and Drug Administration (USFDA) to treat insomnia, including first-generation histamine antagonists like doxepin, benzodiazepines (BZDs), non-BZD hypnotics (often referred to as “Z-drugs”), Dual Orexin Receptor Antagonists like Suvorexant (DORA), and melatonin receptor agonists like Ramelteon. Additionally, other medications may be used off-label. While the guidelines list medications for insomnia, they don’t recommend specific ones due to limited evidence of their effectiveness and risks.⁵

The AASM provides recommendations on specific medications for treating different types of insomnia—sleep onset and sleep maintenance. Certain medications, such as certain BZD receptor agonists and BZDs, are suggested for both types of insomnia. Zaleplon, Triazolam, and Ramelteon are recommended for sleep-onset insomnia, while suvorexant and doxepin are suggested for sleep-maintenance insomnia. However, medications like Trazodone, Tiagabine, Diphenhydramine, Melatonin, L-tryptophan, and Valerian are not recommended (Table 1).

These recommendations are considered “weak” due to limitations in confidence regarding efficacy data, quality, risks, and patient preferences, rather than because the medications are ineffective for treating insomnia.^7,8

HERBS USED IN THE TREATMENT FOR INSOMNIA

Traditional ayurvedic practices emphasize a comprehensive approach to addressing sleep disorders, incorporating various techniques such as physical treatments, psychological interventions, medicinal remedies, dietary adjustments, prayer, and yoga. While classical ancient literature outlines herbal formulations for sleep disorders, contemporary markets offer additional formulations not documented in ancient texts. Numerous studies have explored the use of herbal extracts to reduce sleep latency, increase sleep duration, and improve sleep quality. However, clinical evidence supporting their effectiveness in treating insomnia is currently lacking. Nevertheless, research has indicated that herbal medicines used for insomnia treatment may work through various mechanisms of action.⁶

For example, components of Ginseng (Withania somnifera L.), Ginkgo biloba L., and St John’s Wort (Hypericum perforatum L.) have been shown to influence the re-uptake of neurotransmitters like norepinephrine, dopamine, and serotonin. Additionally, extracts of Jujube seeds and Valerian (Valeriana officinalis L.) directly interact with serotonin receptors, and Griffonia simplicifolia Baill. contains 5-hydroxytryptophan, a natural precursor of serotonin. L-theanine, found in green tea, has been found to potentiate GABA, dopamine, and serotonin receptors and inhibit glutamate reuptake (Table 2). Active components of lavender (Lavandula angustifolia Miller) can bind to glutamate N-methyl-D-aspartate receptors and serotonin transporters. Furthermore, several herbal substances may interact with glutamic acid decarboxylase or modulate GABA and serotonin receptors.⁶

ADJUVANT THERAPIES FOR INSOMNIA

Cognitive-behavioral therapy and pharmacotherapy stand out as the only two treatments with robust evidence supporting their efficacy in managing insomnia. While numerous clinical trials have independently assessed the effectiveness of CBT and medication, few have directly compared their individual and combined effects on insomnia. Overall, the limited available evidence suggests that both modalities yield short-term effectiveness, with medication offering rapid symptom relief, albeit often without sustained benefits post-treatment. In contrast, CBT may require more time to produce results initially but tends to deliver longer-lasting benefits. Combining CBT with medication seems to offer some advantages in the early stages of treatment, but the long-term outcomes vary among patients.^5,8

American Academy of Sleep Medicine guidelines on the psychological and behavioral treatments of insomnia recommend non-pharmacological and adjuvant therapies with medicines. These recommendations are based on a systematic evaluation of clinical trials, and the evidence is evaluated using the Grading of Recommendations Assessment Development and Evaluation (GRADE) process.^7,10 Help clinicians treat patients with chronic insomnia disorder (Table 3).

The interventions suggested in this guideline are designed to fulfill the needs of the majority of patients in a range of circumstances. Like a quality metric, a “strong” suggestion denotes advice that physicians should almost always follow (Fig. 2).

Mindfulness therapies have also been elaborated in Indian studies, which involve meditation and yoga and their effects on resolving factors related to sleep disorders, maintenance, and onset of sleep. Many mindfulness therapies, involving meditation and yoga, have been developed for treating insomnia. However, the available studies and evidence are insufficient. Therefore, larger-scale studies and trials should be conducted to generate more robust evidence in this area.

Cyclic meditation (CM) is a technique combining yoga postures interspersed with supine rest. The combination is based on ancient Indian texts. During the practice, participants maintained closed eyes and followed pre-recorded instructions emphasizing a slow, mindful approach with relaxation. The session commences with reciting a verse from the yoga text Mandukya Upanisad for 40s, followed by isometric muscle contractions throughout the body, culminating in supine rest for 1 min. Participants then transition to standing in tadasana, centering their weight evenly for 2 min. This is followed by specific postures, including bending to the right (Ardhakaticakrasana) for 80 s, a 70-s pause in tadasana for relaxation and awareness, bending to the left (Ardhakaticakrasana) for 80s, another 70s pause, forward bending (Padahastasana) for 80s, another 70s pause, and backward bending (Ardhacakrasana) for 80s. The session concluded with a slow descent into a supine posture, with instructions to sequentially relax different body parts over 10 min. Postures are performed slowly, with a heightened awareness of bodily sensations. The total duration of the practice is 22 minutes and 30 seconds. Cyclic meditation appeared to increase slow-wave sleep and lower the percentage of time in rapid-eye-movement sleep. Also, the number of awakenings per hour is less. The practice of cyclic meditation twice a day appears to improve the objective and subjective quality of sleep the following night.¹²

Yoga practice has demonstrated a significant reduction in work stress, anxiety, muscle fatigue, and emotional exhaustion while enhancing sleep quality, self-care, coping skills, and overall well-being. Previous research indicates that yoga decreases sympathetic nervous system activity, increases parasympathetic activity, and balances autonomic nervous system reactivity. Moreover, it has been shown to boost the secretion of GABA, a neurotransmitter associated with relaxation. These findings suggest that the increase in parasympathetic activity, decrease in sympathetic activity, and heightened GABA secretion following yoga practice may contribute to stress reduction and improved sleep quality. Additionally, the elevation in positive affect and self-compassion, along with the suppression of the posterior hypothalamus and salivary cortisol levels post-yoga, may also play crucial roles in stress reduction. However, while these mechanisms offer insights, a comprehensive understanding of how yoga intervention reduces stress and enhances sleep quality remains elusive. Yoga can be used and can be adopted as a cost-effective, community-based, non-pharmacological tool for the treatment of insomnia.^10,11

The review has explored various maintenance strategies and the potential for alternative treatment sequences to improve outcomes. For instance, patients who don’t respond adequately or achieve remission with initial therapy might benefit from a second-level intervention, which could involve either adding to or switching their treatment approach. A patient initially treated with CBT and other adjuvant therapies might transition to medication, while someone initially treated with medication might switch to CBT or herbal treatments. In making clinical decisions about initial treatment, practical factors such as the availability and acceptability of treatment options, along with clinical considerations like the nature of insomnia (acute vs chronic), previous treatment experiences, comorbidities, and evidence of efficacy, should also be considered.

CONCLUSION

Various modalities of insomnia therapy have unique approaches, with evidence demonstrating their practices and benefits. Currently, treating insomnia involves a variety of methods, and over time, it should be noted that integrating different treatment methodologies can yield better patient outcomes. The literature review indicates that insomnia treatment should not be confined to one modality; exploring all possible approaches, including pharmacotherapy, herbal therapy, and adjuvant therapy, is essential for treating chronic insomnia. Given the limited evidence available for an integrated approach, combining different treatments may lead to better outcomes and benefits for patients. Therefore, a study is needed to assess the various treatment modalities and approaches to generate evidence in these areas.

ORCID

Abhishek M Bulla https://orcid.org/0009-0008-2361-3842

Puneet K Nagendra https://orcid.org/0000-0002-9887-3699

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