The neurobiology, investigation, and treatment of chronic insomnia

Ms. F, a 42-year-old divorced woman, presents for evaluation of chronic insomnia. She complains of difficulty falling asleep, often 30 minutes or longer, and difficulty maintaining sleep during the night, with frequent awakenings that often last 30 minutes or longer. These symptoms occur nearly every night, with only one or two “good” nights per month. She typically goes to bed around 10:00 p.m. to give herself adequate time for sleep, and she gets out of bed around 7:00 a.m. on work days and as late as 9:00 a.m. on weekends. Her nighttime sleep problems result in daytime irritability and difficulty focusing and organizing her thoughts, which subjectively impair her work as an administrative assistant, although her performance evaluations have been satisfactory. She says that she has “no energy for anything extra,” that her house is a mess, and that she routinely declines invitations to join social and even family activities. Her insomnia began approximately 5 years ago during a period of increased life stress related to a difficult divorce and a job change. At that time she was diagnosed with major depression and was started on a successful trial of escitalopram, which she continues at a dose of 10 mg/day. Her current symptoms are distinct from those that were associated with her episode of major depression. She denies pervasive sadness or loss of interest, but she is very frustrated with her inability to function more effectively, which she attributes to her insomnia. In fact, she believes that her cognitive difficulties and irritability are most noticeable after nights of particularly poor sleep. Her medical history is unremarkable other than a past history of Graves’ disease. She has been treated with levothyroxine for the past 15 years. How should Ms. F be evaluated? What medical testing, if any, would be appropriate? What factors should be considered in formulating a treatment plan? What treatments would be appropriate?

Insomnia disorder is defined as difficulty in falling asleep, maintaining sleep, and early morning awakenings. Common daytime consequences experienced are fatigue, mood instability and impaired concentration. In chronic insomnia these symptoms persist over a period of at least three months. Chronic insomnia can also be a symptom of a variety of disorders. The pathophysiology of insomnia is theorised as a disorder of nocturnal and daytime hyper-arousal as a result of increased somatic, cortical and cognitive activation. The causes of insomnia can be categorized into situational, medical, psychiatric and pharmacologically-induced. To diagnose insomnia, it is required to evaluate the daytime and nocturnal symptoms, as well as psychiatric and medical history. The Diagnostic and Statistical Manual 5 Criteria (DSM-5) also provides guidelines and criteria to be followed when diagnosing insomnia disorder. Goals of treatment for insomnia disorder are to correct the underlying sleep complaint and this, together with insomnia symptoms, their severity and duration, as well as co-morbid disorders will determine the choice of treatment. In the majority of patients, insomnia can be treated without pharmacological therapy and cognitive behavioural therapy is considered first-line therapy for all patients with insomnia. The most common pharmacological insomnia treatments include benzodiazepines and benzodiazepines receptor agonists. To avoid tolerance and dependence, these hypnotics are recommended to be used at the lowest possible dose, intermittently and for the shortest duration possible. A combination of cognitive behavioural therapy and pharmacological treatment options is recommended for chronic insomnia.

The mental health community: An underserved and undertreated population: Insomnia management paramount to mental health

Advances in the basic science of sleep/wake neurophysiology are driving the exploration of new pharmacologic approaches with continued improvement in efficacy and safety.

Insomnia is highly prevalent, has associated daytime consequences which impair job performance and quality of life, and is associated with increased risk of comorbidities including depression. These practice parameters provide recommendations regarding behavioral and psychological treatment approaches, which are often effective in primary and secondary insomnia. These recommendations replace or modify those published in the 1999 practice parameter paper produced by the American Sleep Disorders Association. A Task Force of content experts was appointed by the American Academy of Sleep Medicine to perform a comprehensive review of the scientific literature since 1999 and to grade the evidence regarding non-pharmacological treatments of insomnia. Recommendations were developed based on this review using evidence-based methods. These recommendations were developed by the Standards of Practice Committee and reviewed and approved by the Board of Directors of the American Academy of Sleep Medicine. Psychological and behavioral interventions are effective in the treatment of both chronic primary insomnia (Standard) and secondary insomnia (Guideline). Stimulus control therapy, relaxation training, and cognitive behavior therapy are individually effective therapies in the treatment of chronic insomnia (Standard) and sleep restriction therapy, multicomponent therapy (without cognitive therapy), biofeedback and paradoxical intention are individually effective therapies in the treatment of chronic insomnia (Guideline). There was insufficient evidence to recommend sleep hygiene education, imagery training and cognitive therapy as single therapies or when added to other specific approaches. Psychological and behavioral interventions are effective in the treatment of insomnia in older adults and in the treatment of insomnia among chronic hypnotic users (Standard).

BACKGROUND Primary insomnia (PI), commonly identified by difficulties in initiating and/or maintaining sleep, negatively impacts both physical and mental health and increases the risk of occupational and vehicular accidents. Previous researches have indicated that shallow needling, a form of acupuncture, may ameliorate symptoms of primary insomnia. Nevertheless, the scientific evidence regarding its efficacy in enhancing sleep quality remains limited. OBJECTIVE This trial aims to assess the therapeutic efficacy of shallow needling in the treatment of chronic primary insomnia in adults. METHODS A single-center, prospective, assessor-blinded, and randomized controlled clinical trial with two parallel arms will be conducted in the Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine. A total of 124 participants with primary insomnia will be randomly divided into control group and treatment group in a ratio of 1:1 (n = 62 for each group). The control group will take eszopiclone orally at 1 mg once a day for 4 weeks. In addition to taking eszopiclone, the treatment group will receive shallow needling therapy once daily, five times a week, for 4 weeks. Data will be collected at three timeslots (pre, post, 4-weeks follow-up) and analyzed using SPSS 23.0. The primary outcome measure is Pittsburgh Sleep Quality Index (PSQI), Secondary outcome measures are Hamilton anxiety scale (HAMA), Insomnia Severity Index (ISI), Serum neurotransmitter detection (including the content of dopamine [DA], norepinephrine [NE], and melatonin [MT]), sleep parameters, and Magnetic Resonance Spectroscopy (MRS) of the thalamus. RESULTS Subject recruitment is currently underway. The first participant was enrolled in August 2023, marking the official start of the experiment. As of the submission of this paper, a total of 120 subjects have participated in this clinical trial. The recruitment is expected to continue until August 2025, at which point the data processing and analysis will commence. CONCLUSIONS This study will evaluate the therapeutic effectiveness and safety of shallow needling in the treatment of chronic insomnia, so as to provide the necessary scientific basis for the clinical application and promotion of shallow needling. The findings of this study may provide a scientific and standardized treatment protocol for shallow needling in adults with chronic insomnia. CLINICALTRIAL ITMCTR2024000409. Registered on 30 August 2024, Version 1.0.

Chronic insomnia afflicts up to 10% of the population in Western industrialized countries. It is characterized by delayed sleep onset, problems in maintaining sleep, early morning awakening or the feeling of non-restorative sleep coupled with significant daytime impairments on an emotional, social or professional level. It can occur as a co-morbid condition in any other medical or mental disorder, but also as a primary condition. Within the last decade new diagnostic and differential diagnostic approaches have been suggested that enhance diagnostic precision. Epidemiological data and data relating to the health care and cost situation of chronic insomnia suggest a huge burden for society. Chronic insomnia leads to a clear-cut increased risk for psychopathology (i. e., affective disorders) and probably also for cardiovascular and metabolic dysfunction. The pathophysiology of the condition is still poorly understood and will profit from integrating modern neuroscientific approaches (animal studies, molecular biology, neuroimaging, neurophysiology, etc.). Current treatment strategies are mainly based on cognitive behavioural interventions (CBT-I) and hypnotic treatment with benzodiazepine receptor agonists and sedating antidepressants. Although the effectiveness of these treatments has been clearly demonstrated, a substantial proportion of patients proves to be treatment-resistant or profits only poorly. The question of long-term pharmaceutical treatment of chronic insomnia, at least in Europe, is unresolved and urgently needs answers. Novel rational treatment avenues require clues on causes and mechanisms from integrated neuroscientific approaches. The important issues concerning insomnia treatment in the future especially in Europe will be reviewed and discussed critically.

Payer Perspective of the American Academy of Sleep Medicine Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia

Pharmacological and non-pharmacological treatments for chronic insomnia in perimenopausal and postmenopausal women: a systematic review and meta-analysis.

Zolpidem, but lemborexant more consistently, showed self-reported and objective benefits compared with placebo in insomnia patients with sleep duration of less than 6 hours per night.

Insomnia and snoring are common sleep disorders. The aim was to investigate the association of having a combination of insomnia symptoms and snoring with comorbidity and daytime sleepiness. The study population comprised 25,901 participants (16-75 years, 54.4% women) from 4 Swedish cities, who answered a postal questionnaire that contained questions on snoring, insomnia symptoms (difficulties initiating and/or maintaining sleep and/or early morning awakening), smoking, educational level, and respiratory and nonrespiratory disorders. Snoring was reported by 4,221 (16.2%), while 9,872 (38.1%) reported ≥ 1 insomnia symptom. A total of 2,150 (8.3%) participants reported both insomnia symptoms and snoring. The association with hypertension (adjusted odds ratio [OR], 1.4; 95% confidence interval [CI], 1.2-1.6), chronic obstructive pulmonary disease (adjusted OR, 1.8; 95% CI, 1.3-2.4), asthma (adjusted OR, 1.9; 95% CI, 1.6-2.3), daytime sleepiness (adjusted OR, 7.9; 95% CI, 7.1-8.8), and the use of hypnotics (adjusted OR, 7.5; 95% CI, 6.1-9.1) was highest for the group with both insomnia symptoms and snoring. Participants with both snoring and insomnia run an increased risk of hypertension, chronic obstructive pulmonary disease, asthma, daytime sleepiness, and use of hypnotics. It is important to consider snoring in patients seeking medical assistance for insomnia and, vice versa, in patients with snoring inquiring about insomnia. Hägg SA, Ilieva E, Ljunggren M, etal. The negative health effects of having a combination of snoring and insomnia. J Clin Sleep Med. 2022;18(4):973-981.

Improving evidence-based practice in the treatment of chronic insomnia: a commentary for Sleep Medicine Reviews on “Chronic hypnotic use: deadly risks, doubtful benefits” (Daniel F. Kripke)

Huberman Lab Podcast #93 Summary and Commentary

Insomnia group therapy

Background Chronic insomnia disorder, defined as difficulty initiating or maintaining sleep, or early morning awakening, ≥3 times/week for ≥3 months, causing daytime consequences, affects up to 45% of patients with coronary heart disease (CHD). This condition increases the risk of adverse cardiovascular outcomes and impairs quality of life, but remains undiagnosed and untreated in this patient group. Sleep has recently been recognized by the ESC and the AHA as a crucial part of cardiovascular health, highlighting the need for treatment of inadequate sleep. Cognitive-behavioral therapy for insomnia (CBT-I) is the gold standard for treating chronic insomnia, but its efficacy has not been investigated in patients with CHD without heart failure. Purpose To investigate the effects of CBT-I on chronic insomnia in patients with CHD, identify factors influencing treatment response, and potential pathophysiological and psychological correlates in terms of insomnia symptom change. We will also simulate the socioeconomic effects of the intervention prior to available outcome data. Methods We will conduct a randomized controlled trial comparing nurse-delivered, protocol-driven, group-based CBT-I over the course of five weeks (Figures 1 & 2) with sleep hygiene advice provided in a booklet as a control condition. In all, we will randomize 64 patients hospitalized with a coronary artery event during the preceding 4 years and who fulfil the diagnostic criteria for chronic insomnia. The study has power to detect a 25% absolute reduction in the primary outcome defined as no longer meeting the criteria for insomnia as assessed by the Bergen Insomnia Scale. Assessments pre-, post-intervention and at six months follow-up include insomnia diagnosis and severity, daytime symptoms (e.g., sleepiness, fatigue), anxiety, depression, metacognitions, quality of life, and blood and hair sampling for measures of inflammation, glycemic control and chronic cortisol exposure. Objective and subjective sleep variables will be assessed by actigraphy and sleep diaries. We will also interview a sample of patients as part of a qualitative study to explore their experience of treatment. A simulation of socioeconomic outcomes will be based on productivity loss and health service utilization. Results The first patient will be randomized in Q2 2024 and we expect the end of study to be Q4 2025. Results will provide new knowledge into the effects of CBT-I in patients with CHD and chronic insomnia, potentially underpinning the implementation of improved care strategies through enhanced sleep management, and may elucidate potential mechanistic pathways linking chronic insomnia and poor CVD outcomes. Conclusion Treating chronic insomnia in CHD patients requires further investigation and this will be the first trial to assess the effectiveness of CBT-I in CHD patients without heart failure. The trial will provide new insights regarding the impact of CBT-I on chronic insomnia in patients with CHD. Study overview. Overview of CBT-I intervention.