A 2023 Update on Managing Insomnia in Primary Care: Insights From an Expert Consensus Group.

Objective: To evaluate the status of management of insomnia disorder, describe gaps in current recognition and treatment, identify current guidance for optimal management, and develop up-to-date educational recommendations for primary care providers.Participants: Four insomnia experts representing primary care, psychiatry, and clinical research were selected based on clinical expertise, educational qualifications, and research experience. A patient with insomnia was also included.Consensus Process: The Insomnia Working Group met in March 2022 to review data on available therapies (including medications approved since publication of current guidelines) and share current best practices for evidence-based multimodal treatment of insomnia disorder.Conclusions: Insomnia is highly prevalent but underdiagnosed and undertreated. It is increasingly recognized as a distinct disorder, not merely a symptom arising secondary to another medical or psychiatric illness. The subtypes of sleep disturbance-reports of difficulty falling or staying asleep, insufficient sleep duration, early waking-and the presence of next-day impairment and common comorbid conditions require a targeted, individualized approach to therapy. Challenges exist in treating insomnia with commonly used on- and off-label drugs, including low-dose antidepressants, benzodiazepines, and benzodiazepine receptor agonists because of the risk of adverse effects, including impaired next-day functioning. The dual orexin receptor antagonists have a novel mechanistic target and offer an alternative pharmacologic choice. Optimal outcomes for insomnia require a comprehensive approach that includes lifestyle and behavioral strategies to mitigate maladaptive thoughts and behaviors related to sleep and selection of pharmacotherapy based on individual patient complaints and characteristics.

Diagnosing and Treating Insomnia in Adults and Older Adults.

Insomnia, the most prevalent sleep-wake disorder, affects 6% to 10% of adults. It may result in interpersonal and occupational problems and has a deleterious effect on quality of life. Patients may experience difficulty with sleep onset, sleep maintenance, or both. Insomnia disorder is commonly comorbid with psychiatric, medical, and neurologic disorders, and insomnia and comorbid conditions have bidirectional relationships. Diagnosis should be based on patient interview, assessment with tools, and use of criteria. Selection of treatment for patients with insomnia should factor in efficacy for the patient's specific complaint as well as other features such as safety profile and abuse liability. Cognitive-behavioral therapy for insomnia is a first-line recommendation by guidelines, but some patients are unable or unwilling to try it or may not respond to it. Older adults with insomnia disorder require careful consideration of medications' risk-benefit profiles.

The Bidirectional Relationship Between Insomnia and Comorbid Disorders.

Insomnia is often comorbid with psychiatric, medical, and neurologic disorders. For years, insomnia was thought to be secondary to various disorders; therefore, it did not receive the attention it needed because the other disorder was viewed as playing the primary role in the insomnia problem. However, our thinking has moved away from treating the other condition to resolve the insomnia toward treating insomnia as a separate condition. Insomnia and comorbid conditions have a bidirectional effect, with the status of each impacting the other, potentially affecting the treatment course and outcome. This report describes conditions that commonly appear in patients with insomnia.

Prevalence, Impact, and Burden of Insomnia and Discussing It With Patients.

Insomnia is the most prevalent sleep-wake disorder, with about one in ten individuals meeting diagnostic criteria. Associated with significant impairment in daytime function, insomnia has a vast societal burden and impact on public health. To arrive at an accurate diagnosis of insomnia disorder, clinicians should conduct an effective interview with patients to assess the complaint and sleep history and use assessment tools as part of the evaluation.

Next-day residual effects of gabapentin, diphenhydramine, and triazolam on simulated driving performance in healthy volunteers: a phase 3, randomized, double-blind, placebo-controlled, crossover trial.

OBJECTIVE: Next-day residual effects of a nighttime dose of gabapentin 250 mg were evaluated on simulated driving performance in healthy participants in a randomized, placebo-controlled, double-blind, multicenter, four-period crossover study that included diphenhydramine citrate 76 mg and triazolam 0.5 mg. METHODS: At treatment visits, participants (n = 59) were dosed at ~23:30, went to bed immediately, and awakened 6.5 h postdose for evaluation. The primary endpoint was the standard deviation of lateral position for the 100-km driving scenario. Additional measures of driving, sleepiness, and cognition were included. RESULTS: Study sensitivity was established with triazolam, which demonstrated significant next-day impairment on all driving endpoints, relative to placebo (p < 0.001). Gabapentin demonstrated noninferiority to placebo on standard deviation of lateral position and speed deviation but not for lane excursions. Diphenhydramine citrate demonstrated significant impairment relative to gabapentin and placebo on speed deviation (p < 0.05). Other comparisons were either nonsignificant or statistically ineligible per planned, sequential comparisons. Secondary endpoints for sleepiness and cognitive performance were supportive of these conclusions. CONCLUSIONS: Together, these data suggest that low-dose gabapentin had no appreciable next-day effects on simulated driving performance or cognitive functioning. Copyright © 2016 John Wiley & Sons, Ltd.

Clinical assessment of excessive daytime sleepiness in the diagnosis of sleep disorders.

Daytime sleepiness is common, but, in some individuals, it can be excessive and lead to distress and impairment. For many of these individuals, excessive daytime sleepiness is simply caused by poor sleep habits or self-imposed sleep times that are not sufficient to maintain alertness throughout the day. For others, daytime sleepiness may be related to a more serious disorder or condition such as narcolepsy, idiopathic hypersomnia, or obstructive sleep apnea. Clinicians must be familiar with the disorders associated with excessive daytime sleepiness and the assessment methods used to diagnose these disorders in order to identify patients who need treatment.

Recommended treatment strategies for patients with excessive daytime sleepiness.

Excessive daytime sleepiness (EDS) is a common and bothersome phenomenon. It can be associated with insufficient sleep syndrome, narcolepsy, idiopathic hypersomnia, obstructive sleep apnea, shift work disorder, Kleine-Levin syndrome, or Parkinson's disease. Once the underlying cause of the excessive sleepiness is determined, clinicians must select the most appropriate behavioral and pharmacologic interventions to reduce daytime sleepiness, alleviate other symptoms, improve functioning, and ensure the safety of patients and those around them. Patient history, adverse effects, and efficacy in specific conditions should be considered in pharmacologic treatment options for patients with EDS.

Home-use servo-ventilation therapy in chronic pain patients with central sleep apnea: initial and 3-month follow-up.

PURPOSE: Opioid treatment of non-malignant chronic pain can result in hypoxemia, hypercarbia, and central sleep apnea. The aim of this study was to determine the initial efficacy of auto servo-ventilation (ASV) and after 3 months of home use. METHODS: This prospective multicenter interventional study recruited chronic pain patients prescribed ≥100 morphine equivalents for at least 4 months. PARTICIPANTS: Following full-night polysomnography (PSG) to confirm the presence of sleep-disordered breathing, patients were randomized to three additional full-night-attended PSGs with continuous positive airway pressure (CPAP), ASV, and servo-ventilation with an initial mandatory pressure support of 6 cm H2O (ASV manual PSmin 6). Following the PSGs, patients were sent home with EncoreAnywhere and ASV with or without mandatory pressure support. RESULTS: Based on the initial PSG studies, CPAP improved but did not normalize the apnea-hypopnea index (AHI), central apnea index (CAI), or hypopnea index (HI), as all remained elevated. Clinically significant reductions were noted after just one night of ASV and ASV manual (PSmin 6). After 3 months of ASV home use, the AHI, CAI, and obstructive apnea index (OAI) were significantly reduced when compared to baseline diagnostic levels and even when compared to respiratory disturbance indices with CPAP treatment. CONCLUSIONS: Initial and home use of ASV for 3 months resulted in significantly lower AHI, CAI, and OAI. This reduction attests to the efficacy of ASV treatment in chronic pain patients on high doses of opioids.

A randomized, double-blind, single-dose, placebo-controlled, multicenter, polysomnographic study of gabapentin in transient insomnia induced by sleep phase advance.

STUDY OBJECTIVES: To evaluate the effects of single doses of gabapentin 250 and 500 mg on polysomnographic (PSG) and participant-reported sleep measures in a 5-h phase advance insomnia model. METHODS: Adults reporting occasional disturbed sleep received gabapentin 500 mg (n = 125), 250 mg (n = 125), or placebo (n = 127) 30 min prior to bedtime and were in bed from 17:00 to 01:00, ∼5 h before their habitual bedtime. Sleep was assessed by PSG, post-sleep questionnaire, and the Karolinska Sleep Diary (KSD). Next-day residual effects (Digit Symbol Substitution Test [DSST] and Stanford Sleepiness Scale [SSS]) and tolerability were assessed. RESULTS: Demographics were comparable among groups. Among PSG endpoints, wake after sleep onset (primary endpoint) (135.7 [placebo], 100.7 [250 mg], and 73.2 [500 mg] min) was significantly lower and total sleep time (TST) (311.4, 356.5, and 378.7 min) significantly greater in both gabapentin groups versus placebo. Latency to persistent sleep was not significantly different among groups. Percent slow wave sleep (12.6%, 15.4%, and 17.0%, respectively) was significantly greater and percent stage 1 (15.1%, 11.8%, and 10.8%, respectively) significantly lower relative to placebo. Gabapentin was associated with significantly higher values of KSD Sleep Quality Index and reported TST versus placebo; no other reported outcomes were significant. Neither gabapentin dose produced evidence of next-day residual effects as measured by DSST and SSS. Adverse events were infrequent (< 5%). CONCLUSION: Participants with occasional disturbed sleep treated with gabapentin showed significantly longer sleep duration and greater depth (versus placebo) in response to a phase advance manipulation known to disrupt sleep maintenance.

A phase 3, double-blind, randomized, placebo-controlled study of armodafinil for excessive sleepiness associated with jet lag disorder.

OBJECTIVE: To assess the effect of armodafinil, the longer-lasting isomer of modafinil, on jet lag disorder. PARTICIPANTS AND METHODS: This double-blind, randomized, parallel-group, multicenter study was conducted between September 18, 2008, and February 9, 2009. Adults with a history of jet lag symptoms on previous flights through multiple time zones flew from the United States to France (a 6-hour time zone change) for a 3-day laboratory-based study period. Participants received armodafinil (50 or 150 mg/d) or placebo each morning. Wakefulness was assessed by the coprimary outcomes, mean sleep latency on the Multiple Sleep Latency Test (MSLT) (average of all MSLT sessions across days 1 and 2) and Patient Global Impression of Severity in relation to jet lag symptoms (averaged across days 1 and 2). RESULTS: A total of 427 participants received armodafinil at 50 mg/d (n=142), armodafinil at 150 mg/d (n=143), or placebo (n=142). Armodafinil at 150 mg/d provided a significant benefit in sleep latency on the MSLT (days 1-2: mean, 11.7 minutes vs 4.8 minutes for placebo; P<.001) and participants' perception of their overall condition in relation to jet lag symptoms (Patient Global Impression of Severity, days 1-2: mean, 1.6 vs 1.9 for placebo; P<.05). The most frequently reported adverse events for armodafinil at 150 mg/d were headache (27%), nausea (13%), diarrhea (5%), circadian rhythm sleep disorder (5%), and palpitations (5%). CONCLUSION: Armodafinil increased wakefulness after eastward travel through 6 time zones. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00758498.

Sleep maintenance insomnia: strengths and weaknesses of current pharmacologic therapies.

BACKGROUND: Although insomnia is highly prevalent, sleep disturbances often go unrecognized and untreated. When insomnia is recognized, considerable emphasis has been placed on improving sleep onset; however, there is growing evidence that improving sleep maintenance is an equally important treatment goal. METHODS: A MEDLINE literature search was performed using the search parameters "insomnia," "zolpidem," "zaleplon," "flurazepam," "estazolam," "quazepam," "triazolam," and "temazepam," as these agents are FDA-approved for the treatment of insomnia. Per reviewer comments, the search criteria was later expanded to include lorazepam. A literature search using the terms "trazodone" and "insomnia" was also performed, as this is the second-most commonly prescribed agent for treating insomnia. Sleep efficacy endpoints from randomized, placebo-controlled clinical trials in adult populations and key review articles published between 1975 and 2004 were included in this review. As only one randomized placebo-controlled trial evaluated trazodone use in primary insomnia, the trazodone search was expanded to include all clinical trials that evaluated trazodone use in insomnia. Relevant texts and other articles that evaluated side effect profiles of these agents were also included, one of which was published in January of 2005. In all publications, impact of treatment on sleep maintenance parameters (wake time after sleep onset, number of awakenings) and measures of next-day functioning were evaluated, in addition to sleep onset parameters (sleep latency, time to sleep onset/induction) and sleep duration data (total sleep time). RESULTS: Many of the currently available agents used to treat insomnia, including the antidepressant trazodone, the non-benzodiazepine hypnotics zolpidem and zaleplon, and some of the benzodiazepines, have not consistently demonstrated effectiveness in promoting sleep maintenance. Furthermore, the benzodiazepines with established sleep maintenance efficacy are associated with next-day sedation, the risk of tolerance and dependence, or both. CONCLUSIONS: New agents that offer relief of sleep maintenance insomnia without residual next day impairment while improving next day function are needed. Several compounds currently under development may offer clinicians a more effective and safer treatment for this common disorder.