Treatment Of Insomnia Research Articles

Progress in GABAA receptor agonists for insomnia disorder

Insomnia is the most common sleep disorder in which an individual has trouble falling or staying asleep. Chronic sleep loss interferes with daily functioning and adversely affects health. The main clinical drugs for insomnia are the positive allosteric modulator of the GABA (gamma-aminobutyric acid) A receptors (GABAARs) at the benzodiazepine site with selectivity of the GABA-α1 receptor. They are divided into benzodiazepine drugs and non-benzodiazepine drugs. Most recently, the first partial positive allosteric modulator of GABAAR Dimdazenil was approved by National Medical Products Administration (NMPA) and launched in China. This review summarized the mechanism of actions of current clinical drugs for insomnia, and the clinical applications of these drugs, which may help to understand their involvement in insomnia, and to search for more selective and potent ligands to be used in the treatment of insomnia.

Insomnia and its treatments—trend analysis and publication profile of randomized clinical trials

This study aimed to describe the publication profile of randomized controlled trials (RCTs) for insomnia. A systematic review of RCTs regarding interventions for non-comorbid insomnia in adults retrieved 132 RCTs: 58 related to pharmacological treatments, 71 to non-pharmacological treatments, and 3 to both interventions. The treatments with the biggest publication profile were digital CBT-I (dCBT-I) (n = 35), in-person CBT-I (n = 28) and zolpidem (n = 22). Regarding dCBT-I, the median publication year is 2019, with 1.13 ± 1.91 RCTs published per year. Regarding zolpidem, the median publication year is 2008, with 0.71 ± 0.97 RCTs per year. Regarding in-person CBT-I, the median publication year is 2018, with 0.90 ± 1.14 RCTs per year. The majority of the available RCTs are on non-pharmacological interventions, particularly CBT-I (mostly in the 2000s) and dCBT-I (mostly in the last decade), although presenting a reduced methodological quality in comparison to pharmacological interventions. These data suggest an increasing focus on non-pharmacological interventions for insomnia.

The Development and Validation of the Beliefs about Baby Crying at Night (BBCN) Scale

ObjectiveWhat are young children trying to express when they cry at night? According to Sadeh, parental beliefs about why their child is crying may play a role in the development and persistence of their child’s insomnia. The aim of this study was to create a scale that specifically assesses these parental interpretations in different dimensions. MethodsChildren aged between 6 months and 3 years with either good sleep habits or behavioural insomnia were recruited. An initial, 20-item scale for the beliefs of why one’s baby is crying at night was developed, with all items on a 7-point Likert span. The results of this scale from a large sample were then submitted to Exploratory (EFA) and confirmatory (CFA) factor analyses to converge on a final version and evaluate its psychometric properties and validity. ResultsAmong the 1009 subjects included in the analyses (46.2% female, mean age : 1.63 ± 0.73, good sleepers n = 425 and bad sleepers n = 584). After the factor analysis was performed, a 14-item scale with 4 subscales quantifying each interpretation type resulted: namely, “Need for attachment” (5 items), “Need to cry before falling asleep” (3 items), “Leaving a child to cry during the night is traumatizing for the child” (4 items) and “Is in pain” (2 items). The CFA further confirmed an appropriate fit. The most divergent subscale between groups was the “Need for attachment” subscale. ConclusionThis study proposes the first scale known to focus exclusively on parent interpretations of their child’s night-time crying, without taking into account their nursing behaviours. It provides a clinical tool for more effectively discussing with parents, in order to address potential dysfunctional beliefs in the context of early childhood insomnia complaints, as well as a research tool for considering cognitive dimensions in the aetiology and treatment of behavioural insomnia.

Zolpidem-related euphoria, addiction and detoxification: A case report and review of the literature.

Zolpidem, a non-benzodiazepine sedative-hypnotic, is considered safer for the treatment of insomnia compared to benzodiazepines. However, in recent years, there have been growing reports of Zolpidem dependence, addiction, and withdrawal symptoms. We reported a case of Zolpidem addiction and successful detoxification, reviewed similar cases in the literature, and proposed a potential mechanism underlying Zolpidem addiction. The patient was a 46-year-old Tibetan woman who had been using Zolpidem intermittently to treat insomnia for at least 8 years. She was overweight, with a BMI of 28.04 kg/m², and had hypertension, diabetes, a 20-year smoking history, and several years of alcohol abuse, often seeking instant gratification. She voluntarily increased both the dosage and frequency of Zolpidem, experiencing euphoria, anxiolysis, and increased appetite at higher doses, which led her to gradually escalate her dosage to 280 mg per day in divided doses. However, upon stopping Zolpidem, she experienced withdrawal symptoms, including insomnia, tension, and palpitations. She was diagnosed with a combination of hypnotic use disorder, anxiety disorder, hypertension, and diabetes. She underwent diazepam replacement therapy, along with antianxiety medications and mindfulness-based cognitive therapy, to address Zolpidem addiction. After 13 days of inpatient treatment, the patient successfully quit Zolpidem. During a 3-month follow-up, she returned to work and remained free from Zolpidem use. We speculate that Zolpidem addiction is likely linked to the drug's euphoric effects and certain patient characteristics, such as sensation-seeking behavior. A comprehensive approach, involving both pharmacological and psychological interventions, is essential for an effective detoxification strategy for Zolpidem addiction.

A clinical algorithm for diagnosis and treatment of insomnia in adults: an updated review.

Difficulty falling asleep and/or maintaining sleep are common complaints in patients visiting medical clinics. Insomnia can occur alone or in combination with other medical or psychiatric disorders. Diagnosis and management of insomnia at times are perplexing. This updated study review aimed at a clinical algorithm for diagnosis and treatment of insomnia in adults. We developed an easy-to-apply algorithm to diagnose and manage insomnia that can be used by general practitioners and non-sleep specialists. To this end, our team reviewed the previous studies to determine the prevalence, evaluation, and treatment of insomnia. We used the results to develop a clinical algorithm for diagnosing and managing insomnia.Insomnia occurs in a short (less than 3months duration) or chronic form (≥3months duration). Insomnia management includes both pharmacological and non-pharmacological interventions. There is ample research evidence for the impact of a variety of non-pharmacological treatments, but both types of treatments can be used for each patient. If there are any contradictions in the diagnosis process, therapists should use objective instruments, such as polysomnography, but they should not be in a hurry to use these instruments.

The Effectiveness of Cognitive Behavioral Therapy on Insomnia Severity Among Menopausal Women: A Scoping Review

This review explores the impact of cognitive behavioral therapy for insomnia (CBT-I) on menopausal women suffering from insomnia. The transition to menopause is often accompanies by sleep disturbances, which significantly affect women’s quality of life. This review applies a scoping approach to evaluate randomized controlled trials (RCTs) focused on CBT-I interventions for insomnia among menopausal women. The included studies examined variations in the number of CBT-I sessions, the duration of interventions, and their delivery methods (face-to-face, online, or telephone-based). The results consistently showed that CBT-I significantly improves sleep quality and reduces insomnia severity in menopausal women. CBT-I was particularly effective compared to other interventions such as sleep restriction therapy and sleep hygiene education. Sleep quality improvements were observed to persist for up to six months after treatment. These findings support the use of CBT-I as a first-line intervention for insomnia in menopausal women, offering a sustainable solution with fewer side effects compared to pharmacological treatments. However, the review also highlights the need for further research on CBT-I’s efficacy in diverse populations, as most studies focused on predominantly white and well-educated women.

Sleep disorders and a review of the uses of valerian, chamomile, lavender and passionflower: Pharmacy students’ knowledge and views

Insomnia is a common sleep disorder that affects the quality and length of sleep. Individuals who suffer from insomnia may encounter daytime fatigue, mood problems, impaired concentration, and increased risk of chronic diseases. This disorder can be acute or chronic. Acute insomnia is short-term and usually triggered by stress or life events, while chronic insomnia is long-term and often associated with other medical or psychological conditions. Insomnia can be treated with medications, lifestyle changes or herbal remedies. Four different herbs are thought of as potential treatment for insomnia: Valerian, Chamomile, Lavender, and Passionflower. This paper analyzes the potential effects of these remedies and their effectiveness in treating insomnia. It also collected data on what pharmacy students know about sleep disorders and their opinions about aspects that affect sleep. A total of 40 students completed the demographic survey questions with a 100% response rate. Of these, 36 answered the five knowledge-based questions (89.5% response rate) and about 35 (88%) completed the opinion questions. The five opinion statements had an average agreement rate of 81.2% among the survey respondents.

Relationship between Vitamin D and Insomnia in Older Adults

Vitamin D is one of the common fat-soluble vitamins, which can be obtained from ultraviolet exposure and intake from particular food or supplementation. Insomnia caused by many reasons like diseases or health status, would also increase possibilities of suffering from other diseases, and has a prevalence to be common among all sorts of people, especially in older adults. Researchers found vitamin D associated with neurotransmitters, oxidative stress and inflammation. Many research also suggest vitamin D are relevant to insomnia, people with low serum vitamin D concentration have a higher possibility to suffer from insomnia, after a period time of supplementation of vitamin D insomnia patients, many of them get improved, but there are no significant difference on some on them either. The mechanism about vitamin D improving insomnia symptoms is not clear, there is no determine recommended dose and duration for patient, and also not enough clinical trials for further exploration. As an auxiliary means of insomnia treatment, vitamin D may have a good performance combined with other therapies. The current review summarizes some mechanism of vitamin D, both positive and negative evidence associated with vitamin D improves insomnia symptom, and have an outlook for the future study on insomnia between vitamin D.

Insomnia treatment effects on negative emotionality among veterans in treatment for alcohol use disorder.

Insomnia symptoms are pervasive and persistent in alcohol use disorder (AUD), though little is known about the mechanisms that underlie this association. We previously found that cognitive behavioral therapy for insomnia (CBT-I) reduced alcohol-related problems among veterans by improving insomnia severity (NCT03806491). In this planned secondary analysis of the same clinical trial data, we tested negative emotionality as one potential mechanism to explain this effect. Specifically, we tested the change in negative emotionality as a mediator of the association between change in insomnia symptoms and alcohol-related outcomes (craving, heavy drinking frequency, and alcohol-related problems). Participants were 67 veterans in treatment for AUD who also met the criteria for insomnia disorder (91% male, 84% White, average age = 46.3 years). Participants were randomized to five sessions of CBT-I or a single-session sleep hygiene control. Assessments occurred at baseline, immediately posttreatment (~6 weeks after baseline), and at 6-week follow-up. Measures included the Insomnia Severity Index, Penn Alcohol Craving Scale, Timeline Followback, and Short Inventory of Problems. We created a latent negative emotionality indicator based on five validated and reliable measures of negative emotionality. Contrary to hypotheses, CBT-I did not improve negative emotionality relative to sleep hygiene control. However, across both treatment conditions, decreases in insomnia symptoms from baseline to posttreatment were associated with concurrent decreases in negative emotionality, which in turn predicted reductions in alcohol craving and heavy drinking. Negative emotionality may help explain links between insomnia symptoms and alcohol-related outcomes.

Evaluation of the effectiveness of cognitive–behavioural therapy for insomnia delivered by nurses and physicians for patients in primary care (the NPD study): protocol for a cluster randomised controlled trial

IntroductionInsomnia is the most common sleep disorder, and it adversely impacts daily living and increases the risk of chronic and acute health problems. Of the few individuals who seek treatment...

Postmortem diphenhydramine blood concentrations in children.

Diphenhydramine has been available for decades in non-prescription formulations for the treatment of allergic reactions, insomnia and symptomology associated with colds. In addition, dimenhydrinate, a precursor to diphenhydramine, is available in preparations for the treatment of nausea and vomiting. Diphenhydramine and other first-generation antihistamines are being replaced by second- and third-generation antihistamines which are associated with fewer side effects, notably the lack of drowsiness; however, there are still a variety of therapeutic uses that have persisted in both adults and children. In this study, postmortem blood concentrations of diphenhydramine were determined, by liquid chromatography tandem mass spectrometry, in seven children with concentrations ranging from 0.051 to 2.6 mg/L. The cause of death in two cases was attributed, at least in part, to diphenhydramine toxicity while diphenhydramine detection in five cases was considered incidental to the cause of death.

Medical Professionals and Pharmacological Intervention for the Treatment of Insomnia: A Cross-Sectional Study

Abstract Objective To explore the preferences of medical practitioners concerning various medications and other remedies to manage insomnia, and to ascertain whether these preferences are associated with their respective medical specialties. Materials and Methods Employing the snowball sampling technique, we administered two versions of a questionnaire to an international group of medical professionals, including trainees and specialists from diverse medical backgrounds. Results Zopiclone, zolpidem, and mirtazapine were evaluated as the most effective treatments for insomnia, while physicians would typically avoid using other tricyclic antidepressants, dual orexin receptor antagonists, and tryptophan for insomnia treatment. Noteworthy statistical correlations between physicians' specialty and preferred drug therapy, were observed in three out of five cases: 1) first-line drug treatment for short-term intervention against insomnia; (2) second-line treatment for long-term intervention; and 3) cases involving the elderly. Discussion Psychiatrists demonstrated a greater preference for antipsychotics and antidepressants for the treatment of insomnia compared with other physicians. Conversely, other medical professionals exhibited a preference for benzodiazepines and Z-drugs (zopiclone and zolpidem). Although Z-drugs were evaluated as the most effective in the treatment of insomnia, in the clinical practice, physicians administer or would administer antidepressant or antipsychotic drugs more often (mirtazapine and quetiapine respectively). Regarding Dual Orexin Receptor Antagonists (DORAs), the high prevalence of “Do not know/No opinion” answers implies that our sample was not familiar with this innovative treatment.

A randomized study on the effect of a wearable device using 0.75 Hz transcranial electrical stimulation on sleep onset insomnia.

The normal transition to sleep is characterized by a reduction in higher frequency activity and an increase in lower frequency activity in frontal brain regions. In sleep onset insomnia these changes in activity are weaker and may prolong the transition to sleep. Using a wearable device, we compared 30min of short duration repetitive transcranial electric stimulation (SDR-tES) at 0.75Hz, prior to going to bed, with an active control at 25Hz in the same individuals. Treatment with 0.75Hz significantly reduced sleep onset latency (SOL) by 53% when compared with pre-treatment baselines and was also significantly more effective than stimulation with 25Hz which reduced SOL by 30%. Reductions in SOL with 25Hz stimulation displayed order effects suggesting the possibility of placebo. No order effects were observed with 0.75Hz stimulation. The decrease in SOL with 0.75Hz treatment was proportional to an individual's baseline wherein those suffering from the longest pre-treated SOLs realized the greatest benefits. Changes in SOL were correlated with left/right frontal EEG signal coherence around the stimulation frequency, providing a possible mechanism and target for more focused treatment. Stimulation at both frequencies also decreased perceptions of insomnia symptoms measured with the Insomnia Severity Index, and comorbid anxiety measured with the State Trait Anxiety Index. Our study identifies a new potential treatment for sleep onset insomnia that is comparably effective to current state-of-practice options including pharmacotherapy and cognitive behavioral therapy and is safe, effective, and can be delivered in the home.

Prevalence and associations of insomnia after COVID-19 infection.

Sleep disturbances in "long COVID" are common, but the associations between the severity of sleep problems and the severity of COVID infection are unclear. We evaluated the prevalence, persistence, comorbidities, and clinical effects of insomnia following recovery from acute COVID-19 infection in a COVID-specific clinic. Inpatients discharged after COVID infection and outpatients referred for persistent post-COVID symptoms were surveyed on insomnia severity (Insomnia Severity Index, ISI), other neuropsychological symptoms, cardiopulmonary symptoms and physiological functions (6 minute walk distance and others), and functional outcome and quality of life (QOL). Multivariable regression models evaluated the severity of ISI against independent variables. A total of 280 patients met criteria at the initial visit. The prevalence of significant insomnia at the initial visit was 50% and 42% at the subsequent visit (obtained in 78 of the 280 patients). Lower age, female sex, non-white race, and non-Hispanic ethnicity were significantly associated with worse initial ISI scores. More severe symptoms of anxiety and depression were strong correlates with worse ISI scores. Interval improvements in insomnia severity correlated with improvements in anxiety and post-traumatic stress disorder (PTSD) scores. Physiological sequelae of infection did not correlate with insomnia at any stage. Initial and persistent insomnia is common in long COVID. Treatment for insomnia with the use of evidence based approaches (such as cognitive behavioral therapy for insomnia) may best suit this particular post-COVID symptom.

An Overview of the Current State of Research on Immune Expression in Acupuncture for Insomnia Based on the Relationship between Sleep and Immunity

Sleep is a resting state under the action of the sleep-wake center, regulated by the nerve, endocrine and immune, and any change in the content of any of the substances involved in sleep may break the delicate balance between them, affecting the normal progression of sleep and thus insomnia. Cytokines are the common language signals of the three major systems of neuro-endocrine-immune, and play an important role in inflammation and immune response. Therefore, the relationship between insomnia and immune factors has also become a hot research topic in recent years. A large number of studies have shown that acupuncture has a clear regulatory effect on immune function, so based on the relationship between sleep and immunity to acupuncture treatment of insomnia as an entry point, to explore the current status of immune research on acupuncture treatment of insomnia, in order to provide certain thinking for the integration of in-depth research afterward.

Music and Sleep Hygiene Interventions for Pregnancy-Related Insomnia: An Online Randomized Controlled Trial.

Approximately 50% to 60% of all pregnant women suffer from insomnia during pregnancy. Pregnancy-related insomnia has been associated with severe outcomes for both mother and child postnatally. Currently, the treatment of pregnancy-related insomnia is often neglected due to a lack of suitable treatments. This online assessor-masked randomized controlled trial aimed to evaluate the effectiveness of music listening and sleep hygiene for treating pregnancy-related insomnia. We recruited first-time pregnant women at the end of the second trimester with a report of poor sleep. Participants in the music and sleep hygiene (MSH) group received standard sleep hygiene advice and were instructed to listen to music daily at bedtime for 4 weeks. They could choose from 6 sleep playlists of different genres. Participants randomized to the sleep hygiene alone (SH) group received standard sleep hygiene only. Primary outcomes were sleep quality measured with the Pittsburgh Sleep Quality Index (PSQI) and insomnia severity measured with the Insomnia Severity Index. gov Identifier: NCT04633395. Among the 98 participants receiving the online intervention, 31 participants in the MSH group (62%) and 40 participants in the SH group (80%) completed the postintervention measurements. Both groups experienced improved sleep quality during the intervention period (PSQI change, -2.10; 95% CI, -3.27 to -0.93; P <.001), with no significant difference between the groups. Similarly, insomnia symptoms were reduced (Insomnia Severity Index change, -3.42; 95% CI, -5.02 to -1.83; P <.001) with no significant difference in the effect between groups. There was a significant difference in adherence to sleep hygiene between the MSH and SH groups (42% vs 8%; P =.007). Sleep quality and insomnia severity can be improved in pregnant women with relatively simple interventions like music listening and sleep hygiene advice. These results align with previous research, but larger trials are recommended to support introduction into clinical practice.

The functional activity of the brain in patients with occupational chronic mercury intoxication against background of the treatment of insomnia disorders

Introduction. In patients with chronic mercury intoxication, insomnia disorders are much more common than in the general population. Persistent emotional disorders in combination with severe sleep disturbances may contribute to the progression of cognitive dysfunction in patients in the late post-exposure period of chronic mercury intoxication. The purpose of the study was to analyze the trend in electroencephalography indices and study cognitive evoked potentials in patients with occupational chronic mercury intoxication to optimize the treatment of insomnia. Materials and methods. Two groups of 30 patients with occupational chronic mercury intoxication, who worked at the enterprises of Usolyekhimprom LLC and Sayanskhimplast OJSC, were examined. In the first group of patients received the first treatment option, the average age was 56±0.71 years, in the second group, cases received the second treatment regimen, were of 57.1±3 years. Before and after treatment, there were carried out neurophysiological studies including polysomnography, electroencephalography, and a study of cognitive evoked potentials P300. Results. After the implementation of the treatment regimen in the first group, positive changes in the main indices of polysomnography were revealed as follows: decrease in the time of falling asleep and time of wakefulness in the bed, increase in total sleep time and the representation of delta sleep, increase in the sleep efficiency index, etc., electroencephalography (decrease in the delta index – rhythm and an increase in the alpha rhythm index), and cognitive evoked potentials (decreased latency and increased P300 amplitude). In the second group, there were registered positive alterations only in three neurophysiological indices: a decrease in the latent period of the 1st stage of sleep, a decline in the delta rhythm index and a fall in P300 latency. Limitations. The results cannot be generalized to workers as the group included only men. Conclusion. According to neurophysiological studies, improvement in polysomnography parameters during the treatment of insomnia in patients in the late post-contact period of chronic mercury intoxication was accompanied by an improvement in concentration and an increase in the rate of psychomotor response.

Challenges in integrating traditional Chinese medicine and gut microbiota research for insomnia treatment

The gut microbiome is an extensive variety of bacteria with a range of metabolic capabilities that can be pathogenic, beneficial, or opportunistic. Changes in the gut microbiota's composition can affect the link between gut integrity and host health as well as cause disruptions to numerous neurological systems. The second most prevalent mental health problem, insomnia has a negative social and economic impact. Currently, it is becoming increasingly obvious how crucial it is to preserve the delicate balance of gut microbiota to treat illness-related symptoms like insomnia. Although traditional Chinese medicine has proposed an effective strategy against insomnia through gut microbiota alteration in animal models, studies in human models are limited. This decreases the predictive value of the studies in terms of human outcomes. This editorial places an emphasis on cultural sensitivity rather than scientific reasoning that promotes the use of traditional Chinese medicine (TCM). We aim to emphasize the concern that promoting TCM could divert resources from conventional medical research, leading to suboptimal care.

A single-arm pilot study of a brief cognitive-behavioral therapy for insomnia intervention among Japanese occupational therapy and physical therapy university students with sleep disturbances

ObjectiveTo evaluate the feasibility of the Sleep Health through University Student Habits (SHUSH) program, a brief sleep improvement intervention based upon principles of cognitive-behavioral therapy for insomnia (CBT-I) developed for Japanese university students.MethodsPretest-posttest, single-arm pilot study design with 3-month follow up was used to evaluate the feasibility of SHUSH. We developed then offered a 90-min sleep education class based upon the two-process model of sleep regulation, sleep restriction, stimulus control, and sleep hygiene. We recommended individualized sleep prescriptions (e.g., prescribed time to bed and prescribed time out of bed) from 11 days of daily sleep diary data. We then offered 15 min of individualized follow-up meetings each week for three consecutive weeks in person or online in which we supported adherence to sleep prescriptions. Fifteen university students with self-reported sleep disturbance (Insomnia Severity Index; ISI score ≥ 9) completed the SHUSH program. Participants were on average age 19.7 years old; nine were women, and they were students in occupational therapy and physical therapy. We assessed validated Japanese versions of sleep-related (e.g., ISI, Sleep hygiene practice scale; SHPS), mental health-related (e.g., Generalized Anxiety Disorder Screener) patient-reported outcomes (PROs) and daily sleep diary variables (e.g., sleep onset latency and sleep efficiency).ResultsComparing baseline and posttest data, a statistically significant difference was observed in insomnia symptom severity, daytime sleepiness, sleep hygiene practices, eveningness to morningness, anxiety, depression, sleep diary improvements (e.g., sleep onset latency, total time in bed, and sleep efficiency). Comparing posttest and 3-mo follow up data (n = 10), a statistically significant difference wasn't observed for most PRO effects. However, there was a statistically significant difference in ineffective sleep behaviors (i.e., SHPS-J). We did observe a rebound effect for some SHPS-J items.ConclusionSHUSH was developed as a brief cognitive-behavioral intervention for insomnia. SHUSH participants showed improvements on sleep-related and mental health-related PROs after 4 weeks of intervention. At 3 months follow-up sleep quality and mental health gains were maintained. SHUSH was a feasible program. Randomized controlled trials are needed to test treatment efficacy on sleep related and mental health related PROs in the future.

Efficacy and safety of auricular acupressure on reduction of estazolam in patients with insomnia: a study protocol for a three-arm, blinded randomized controlled trial

BackgroundDrug-dependent insomnia refers to insomnia patients taking sedatives and sleeping pills regularly for a long period. Auricular acupressure (AA) has attracted growing attention as a complementary treatment for insomnia. Nevertheless, there is a lack of rigorous studies evaluating AA specifically for estazolam-dependent insomnia. Our proposed trial aims to assess the therapeutic effect of AA on estazolam-dependent insomnia.MethodsThis study is a randomized, single-blinded, three-arm controlled trial. No less than 108 participants will be randomized into one of three groups: AA group, sham auricular acupressure (SAA) group, and conventional dosage reduction group. All treatments will be administered for 4 weeks, with a follow-up period of 1 month. The primary clinical outcomes will be estazolam dosing and reduction rates, serum gamma-aminobutyric acid (GABA) and cortisol (CORT) levels. Secondary outcomes will concern the Pittsburgh sleep quality index (PSQI) and Benzodiazepine Withdrawal Symptom Questionnaire (BWSQ). Both intention-to-treat and per-protocol analyses will be performed, with the significance level determined as 5%.DiscussionThe study results will provide evidence on the efficacy and safety of AA in managing estazolam-dependent insomnia by analyzing its immediate effect, time-effect relationship, and reduction of estazolam use.Trial RegistrationClinicaltrials.gov (identification number: NCT06258226; Registered 5 February 2024, https://clinicaltrials.gov/ct2/show/NCT06258226).