Insomnia Treatments: New Perspectives

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Clinical Neurology".

Deadline for manuscript submissions: closed (15 February 2023) | Viewed by 50056

Special Issue Editor


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Guest Editor
Sleep Medicine Center, University of Washington, Seattle, WA, USA
Interests: sleep medicine; sleep duration; sleep epidemiology; narcolepsy; central nervous system hypersomnia

Special Issue Information

Dear Colleagues,

Sleep disorders are among the most common medical complaints worldwide, affecting approximately 30% of the general population. Insomnia is the most common sleep disorder and the clinical diagnostic criteria defining insomnia disorder include not only sleep disruption but also consequent daytime impairment. Insomnia can also have devastating effects on human health, including a higher risk of obesity, cardiovascular disease, diabetes, alcohol abuse, and incident and recurrent depression.

The identification of a person’s specific insomnia symptoms can help guide treatments. While cognitive behavioral therapy for insomnia (CBT-I) is considered first-line treatment, not all patients respond to or have access to CBT-I. Pharmacological treatments include several different drug classes, such as benzodiazepines; non-BZD hypnotic “Z-drugs,” such as zolpidem or eszopiclone; dual orexin receptor antagonists; melatonin receptor agonists; histamine antagonists; and classes, such as sedating antidepressants.

Insomnia management is complex and changed significantly in the past decade. Several new pharmacologic treatments have been introduced, expanding the scope of options for therapy. Y the availability of newer pharmacologic therapies and optimal treatments for specific insomnia outcomes is not well-defined, and there is a dire need for improved education on treatment options and patient-physician dialogue.

Submissions of original research articles on the clinical management of insomnia are welcomed for this Special Issue. In particular, reviews focusing on the latest pharmacologic treatment options are encouraged.

All papers submitted to this Special Issue are reviewed by independent referees, and the final decision is made by a JCM Editorial Board Member who does not have any conflicts of interest with the submission.

Prof. Dr. Nathaniel Watson
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • insomnia
  • insomnia medications
  • drug therapy
  • daytime function
  • sleep disorders

Published Papers (9 papers)

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Editorial

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4 pages, 323 KiB  
Editorial
Insomnia and Death Anxiety: A Theoretical Model with Therapeutic Implications
by Nathaniel F. Watson
J. Clin. Med. 2023, 12(9), 3250; https://doi.org/10.3390/jcm12093250 - 02 May 2023
Viewed by 1387
Abstract
Insomnia is common, growing in prevalence [...] Full article
(This article belongs to the Special Issue Insomnia Treatments: New Perspectives)
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Research

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18 pages, 3808 KiB  
Article
Use of Daridorexant among Patients with Chronic Insomnia: A Retrospective Observational Analysis
by Scott G. Williams and Domingo Rodriguez-Cué
J. Clin. Med. 2023, 12(9), 3240; https://doi.org/10.3390/jcm12093240 - 01 May 2023
Cited by 1 | Viewed by 11198
Abstract
Insomnia is the most prevalent sleep disorder, affecting millions worldwide and taking a heavy toll on patient health with significant social and economic impact. Even though there are multiple different types of insomnia medications and behavioral therapies, there are still many individuals for [...] Read more.
Insomnia is the most prevalent sleep disorder, affecting millions worldwide and taking a heavy toll on patient health with significant social and economic impact. Even though there are multiple different types of insomnia medications and behavioral therapies, there are still many individuals for whom treatment remains ineffective. The objective of this retrospective study was to analyze the effectiveness of daridorexant in a cohort of chronic insomnia patients largely transitioned from GABA-A positive allosteric modulators (benzodiazepines, zolpidem or eszopiclone) or other frequently prescribed insomnia medications (including trazodone, atypical antipsychotics or tricyclic antidepressants). A total of 86 patients were treated in the course of ordinary practice and the primary analytic endpoint was the change in Insomnia Severity Index (ISI) score following ≥ 30 nights of treatment with daridorexant. Results from 80 of the 86 patients with full data (65% female, mean age 53.5 years, 18.8% with comorbid obstructive sleep apnea, 91.3% transitioned from a different medication) showed a mean improvement in ISI score of 7.0 ± 0.54 points (SEM) (p < 0.0001) from 18.0 to 11.0. Overall, 78% of the cohort demonstrated a clinically meaningful improvement as defined by at least a six-point drop in ISI. Total sleep time increased by 54 ± 1.0 min (SEM) (p < 0.0001) from 6.0 h to 6.9 h. Mean sleep latency decreased by 23.9 ± 2.4 min (SEM) (p < 0.0001) from 58.8 min to 34.9 min. Wake after sleep onset decreased by 31.6 ± 3.2 min (SEM) (p < 0.001) from 42.8 min to 11.3 min. Sleep efficiency improved by 10.5 ± 1.1% (SEM) (p < 0.0001) from 79.3% to 89.8%. No significant adverse events were noted during the study duration. Keeping in mind this study’s limitations, these data suggest that for insomnia patients with an incomplete response to current therapy, switching to daridorexant is safe and may be an effective alternative treatment. Full article
(This article belongs to the Special Issue Insomnia Treatments: New Perspectives)
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15 pages, 1173 KiB  
Article
Do Insomnia Treatments Improve Daytime Function?
by Nathaniel F. Watson, Suzanne M. Bertisch, Charles M. Morin, Rafael Pelayo, John W. Winkelman, Phyllis C. Zee and Andrew D. Krystal
J. Clin. Med. 2023, 12(9), 3089; https://doi.org/10.3390/jcm12093089 - 24 Apr 2023
Cited by 3 | Viewed by 4671
Abstract
A scientific advisory panel of seven U.S. and Canadian sleep experts performed a clinical appraisal by comparing general medical opinion, assessed via a survey of practicing clinicians, regarding insomnia treatment, with the available scientific evidence. This clinical appraisal focuses on the specific statement, [...] Read more.
A scientific advisory panel of seven U.S. and Canadian sleep experts performed a clinical appraisal by comparing general medical opinion, assessed via a survey of practicing clinicians, regarding insomnia treatment, with the available scientific evidence. This clinical appraisal focuses on the specific statement, “Treatments for insomnia have uniformly been shown to significantly improve the associated daytime impairment seen with insomnia.” The advisory panel reviewed and discussed the available body of evidence within the published medical literature to determine what discrepancies may exist between the currently published evidence base and general medical opinion. The advisory panels’ evaluation of this statement was also compared with the results of a national survey of primary care physicians, psychiatrists, nurse practitioners, physician assistants, and sleep specialists in the United States. Contrary to general medical opinion, the expert advisory panel concluded that the medical literature did not support the statement. This gap highlights the need to educate the general medical community regarding insomnia treatment efficacy in pursuit of improved treatment outcomes. Full article
(This article belongs to the Special Issue Insomnia Treatments: New Perspectives)
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15 pages, 1560 KiB  
Article
Wake Up America: National Survey of Patients’ and Physicians’ Views and Attitudes on Insomnia Care
by Ruth M. Benca, Suzanne M. Bertisch, Ajay Ahuja, Robin Mandelbaum and Andrew D. Krystal
J. Clin. Med. 2023, 12(7), 2498; https://doi.org/10.3390/jcm12072498 - 25 Mar 2023
Cited by 1 | Viewed by 1806
Abstract
While both patients and physicians consider sleep to be important, sleep health may not receive appropriate consideration during patient visits with health care professionals (HCPs). We completed the first large-scale survey of people with trouble sleeping (PWTS) and physicians who treat insomnia to [...] Read more.
While both patients and physicians consider sleep to be important, sleep health may not receive appropriate consideration during patient visits with health care professionals (HCPs). We completed the first large-scale survey of people with trouble sleeping (PWTS) and physicians who treat insomnia to understand their perspectives and potential discrepancies between them. The Harris Poll conducted online surveys of adult PWTS and HCPs (primary care physicians [PCPs] and psychiatrists) in the United States from September to October 2021. Respondents included 1001 PWTS, 300 PCPs, and 152 psychiatrists. Most HCPs agreed that sleep is critical to good health, yet very few reported routinely conducting full sleep histories on their patients. Approximately 30% of PWTS reported that their PCP never asks about sleep; zero HCPs in this survey reported “never” inquiring. Few HCPs reported being “very satisfied” with current treatment options; 50% of PCPs reported their patients being satisfied. Two-thirds of PWTS did not believe current treatment options adequately improved their sleep. This survey provides evidence that both PWTS and physicians agreed on the importance of sleep, but that treatment is often perceived as ineffective. This survey identifies a need for HCPs to address insomnia management and treatment gaps. Full article
(This article belongs to the Special Issue Insomnia Treatments: New Perspectives)
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13 pages, 1208 KiB  
Article
The Associations between Insomnia Severity and Health Outcomes in the United States
by François-Xavier Chalet, Paul Saskin, Ajay Ahuja, Jeffrey Thompson, Abisola Olopoenia, Kushal Modi, Charles M. Morin and Emerson M. Wickwire
J. Clin. Med. 2023, 12(6), 2438; https://doi.org/10.3390/jcm12062438 - 22 Mar 2023
Cited by 2 | Viewed by 2731
Abstract
Little is known about the associations between insomnia severity, insomnia symptoms, and key health outcomes. Using 2020 United States National Health and Wellness Survey (NHWS) data, we conducted a retrospective, cross-sectional analysis to determine the associations between insomnia severity and a number of [...] Read more.
Little is known about the associations between insomnia severity, insomnia symptoms, and key health outcomes. Using 2020 United States National Health and Wellness Survey (NHWS) data, we conducted a retrospective, cross-sectional analysis to determine the associations between insomnia severity and a number of health outcomes germane to patients (health-related quality of life (HRQoL), employers and government (workplace productivity), and healthcare payers (healthcare resource utilization (HCRU)). The Insomnia Severity Index (ISI) questionnaire was used to evaluate overall insomnia severity. HRQoL was assessed using the physical and mental component summary scores of the Short Form-36v2 (SF-36v2) questionnaire, and health utility status was measured using the Short Form-6D (SF-6D) and EuroQoL-5D (EQ-5D) questionnaires. Workplace productivity was measured using the Work Productivity and Activity Impairment (WPAI) questionnaire. After adjusting for confounders, greater insomnia severity was significantly associated with worsened quality of life, decreased productivity, and increased HCRU in an apparent linear fashion. These findings have important implications for future research, including the need for specific assessment of insomnia symptoms and their impact on key health outcomes. Full article
(This article belongs to the Special Issue Insomnia Treatments: New Perspectives)
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Review

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10 pages, 1248 KiB  
Review
Should Trazodone Be First-Line Therapy for Insomnia? A Clinical Suitability Appraisal
by Rafael Pelayo, Suzanne M. Bertisch, Charles M. Morin, John W. Winkelman, Phyllis C. Zee and Andrew D. Krystal
J. Clin. Med. 2023, 12(8), 2933; https://doi.org/10.3390/jcm12082933 - 18 Apr 2023
Cited by 4 | Viewed by 18926
Abstract
Trazodone is one of the most commonly used prescription medications for insomnia; however, some recent clinical guidelines do not recommend its use for treating insomnia. This clinical appraisal critically reviews the scientific literature on trazodone as a first-line treatment for insomnia, with the [...] Read more.
Trazodone is one of the most commonly used prescription medications for insomnia; however, some recent clinical guidelines do not recommend its use for treating insomnia. This clinical appraisal critically reviews the scientific literature on trazodone as a first-line treatment for insomnia, with the focus statement “Trazodone should never be used as a first-line medication for insomnia.” In addition, field surveys were sent to practicing physicians, psychiatrists, and sleep specialists to assess general support for this statement. Subsequently, a meeting with a seven-member panel of key opinion leaders was held to discuss published evidence in support and against the statement. This paper reports on the evidence review, the panel discussion, and the panel’s and healthcare professionals’ ratings of the statement’s acceptability. While the majority of field survey responders disagreed with the statement, the majority of panel members agreed with the statement based on the limited published evidence supporting trazodone as a first-line agent as they understood the term “first-line agent”. Full article
(This article belongs to the Special Issue Insomnia Treatments: New Perspectives)
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22 pages, 682 KiB  
Review
Alliance for Sleep Clinical Practice Guideline on Switching or Deprescribing Hypnotic Medications for Insomnia
by Nathaniel F. Watson, Ruth M. Benca, Andrew D. Krystal, William V. McCall and David N. Neubauer
J. Clin. Med. 2023, 12(7), 2493; https://doi.org/10.3390/jcm12072493 - 25 Mar 2023
Cited by 5 | Viewed by 12457
Abstract
Determining the most effective insomnia medication for patients may require therapeutic trials of different medications. In addition, medication side effects, interactions with co-administered medications, and declining therapeutic efficacy can necessitate switching between different insomnia medications or deprescribing altogether. Currently, little guidance exists regarding [...] Read more.
Determining the most effective insomnia medication for patients may require therapeutic trials of different medications. In addition, medication side effects, interactions with co-administered medications, and declining therapeutic efficacy can necessitate switching between different insomnia medications or deprescribing altogether. Currently, little guidance exists regarding the safest and most effective way to transition from one medication to another. Thus, we developed evidence-based guidelines to inform clinicians regarding best practices when deprescribing or transitioning between insomnia medications. Five U.S.-based sleep experts reviewed the literature involving insomnia medication deprescribing, tapering, and switching and rated the quality of evidence. They used this evidence to generate recommendations through discussion and consensus. When switching or discontinuing insomnia medications, we recommend benzodiazepine hypnotic drugs be tapered while additional CBT-I is provided. For Z-drugs zolpidem and eszopiclone (and not zaleplon), especially when prescribed at supratherapeutic doses, tapering is recommended with a 1–2-day delay in administration of the next insomnia therapy when applicable. There is no need to taper DORAs, doxepin, and ramelteon. Lastly, off-label antidepressants and antipsychotics used to treat insomnia should be gradually reduced when discontinuing. In general, offering individuals a rationale for deprescribing or switching and involving them in the decision-making process can facilitate the change and enhance treatment success. Full article
(This article belongs to the Special Issue Insomnia Treatments: New Perspectives)
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11 pages, 784 KiB  
Review
What Should Be the Focus of Treatment When Insomnia Disorder Is Comorbid with Depression or Anxiety Disorder?
by Charles M. Morin, Suzanne M. Bertisch, Rafael Pelayo, Nathaniel F. Watson, John W. Winkelman, Phyllis C. Zee and Andrew D. Krystal
J. Clin. Med. 2023, 12(5), 1975; https://doi.org/10.3390/jcm12051975 - 02 Mar 2023
Cited by 5 | Viewed by 5535
Abstract
Insomnia is a significant, highly prevalent, persistent public health problem but often remains undiagnosed and untreated. Current treatment practices are not always evidence-based. When insomnia is comorbid with anxiety or depression, treatment often targets that comorbid condition with the expectation that improvement of [...] Read more.
Insomnia is a significant, highly prevalent, persistent public health problem but often remains undiagnosed and untreated. Current treatment practices are not always evidence-based. When insomnia is comorbid with anxiety or depression, treatment often targets that comorbid condition with the expectation that improvement of the mental health condition will generalize to sleep symptoms. An expert panel of seven members conducted a clinical appraisal of the literature regarding the treatment of insomnia when comorbid anxiety or depression are also present. The clinical appraisal consisted of the review, presentation, and assessment of current published evidence as it relates to the panel’s predetermined clinical focus statement, “Whenever chronic insomnia is associated with another condition, such as anxiety or depression, that psychiatric condition should be the only focus of treatment as the insomnia is most likely a symptom of the condition”. The results from an electronic national survey of US-based practicing physicians, psychiatrists, and sleep (N = 508) revealed that >40% of physicians agree “at least somewhat” that treatment of comorbid insomnia should focus solely on the psychiatric condition. Whereas 100% of the expert panel disagreed with the statement. Thus, an important gap exists between current clinical practices and evidence-based guidelines and more awareness is needed so that insomnia is treated distinctly from comorbid anxiety and depression. Full article
(This article belongs to the Special Issue Insomnia Treatments: New Perspectives)
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12 pages, 570 KiB  
Review
Long-Term Use of Insomnia Medications: An Appraisal of the Current Clinical and Scientific Evidence
by Phyllis C. Zee, Suzanne M. Bertisch, Charles M. Morin, Rafael Pelayo, Nathaniel F. Watson, John W. Winkelman and Andrew D. Krystal
J. Clin. Med. 2023, 12(4), 1629; https://doi.org/10.3390/jcm12041629 - 17 Feb 2023
Cited by 3 | Viewed by 6119
Abstract
While evidence supports the benefits of medications for the treatment of chronic insomnia, there is ongoing debate regarding their appropriate duration of use. A panel of sleep experts conducted a clinical appraisal regarding the use of insomnia medications, as it relates to the [...] Read more.
While evidence supports the benefits of medications for the treatment of chronic insomnia, there is ongoing debate regarding their appropriate duration of use. A panel of sleep experts conducted a clinical appraisal regarding the use of insomnia medications, as it relates to the evidence supporting the focus statement, “No insomnia medication should be used on a daily basis for durations longer than 3 weeks at a time”. The panelists’ assessment was also compared to findings from a national survey of practicing physicians, psychiatrists, and sleep specialists. Survey respondents revealed a wide range of opinions regarding the appropriateness of using the US Food and Drug Administration (FDA)-approved medications for the treatment of insomnia lasting more than 3 weeks. After discussion of the literature, the panel unanimously agreed that some classes of insomnia medications, such as non-benzodiazepines hypnotics, have been shown to be effective and safe for long-term use in the appropriate clinical setting. For eszopiclone, doxepin, ramelteon and the newer class of dual orexin receptor antagonists, the FDA label does not specify that their use should be of a limited duration. Thus, an evaluation of evidence supporting the long-term safety and efficacy of newer non-benzodiazepine hypnotics is timely and should be considered in practice recommendations for the duration of pharmacologic treatment of chronic insomnia. Full article
(This article belongs to the Special Issue Insomnia Treatments: New Perspectives)
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