The European Insomnia Guideline 2023 PDF

Received: 16 August 2023 Accepted: 21 August 2023 DOI: 10.1111/jsr.14035 REVIEW ARTICLE The European Insomnia Guideline: An update on the diagnosis and treatment of insomnia 2023 Dieter Riemann 1,2 | Colin A. Espie 3 | Ellemarije Altena 4...

Received: 16 August 2023 Accepted: 21 August 2023 DOI: 10.1111/jsr.14035 REVIEW ARTICLE The European Insomnia Guideline: An update on the diagnosis and treatment of insomnia 2023 Dieter Riemann 1,2 | Colin A. Espie 3 | Ellemarije Altena 4 | Erna Sif Arnardottir 5,6 | Chiara Baglioni 7 | Claudio L. A. Bassetti 8 | Celyne Bastien 9 | Natalija Berzina 10 | Bjørn Bjorvatn 11 | Dimitris Dikeos 12 | 13 14 15 Leja Dolenc Groselj | Jason G. Ellis | Diego Garcia-Borreguero | Pierre A. Geoffroy 16 | Michaela Gjerstad 17 | Marta Gonçalves 18 | 19 Elisabeth Hertenstein | Kerstin Hoedlmoser 20 | Tuuliki Hion 21 | Brigitte Holzinger 22 | Karolina Janku 23 | Markus Jansson-Fröjmark 24,25 | 26 24,25 27 Heli Järnefelt | Susanna Jernelöv | Poul Jørgen Jennum | 28 3,8,19 3 Samson Khachatryan | Lukas Krone | Simon D. Kyle | Jaap Lancee 29 | Damien Leger 30 | Adrian Lupusor 31 | Daniel Ruivo Marques 32,33 | Christoph Nissen 34 | Laura Palagini 35 | 36 34 37 Tiina Paunio | Lampros Perogamvros | Dirk Pevernagie | 20 Manuel Schabus | Tamar Shochat 38 | Andras Szentkiralyi 39 | 40,41 Eus Van Someren | Annemieke van Straten 42 | Adam Wichniak 43 | Johan Verbraecken 44 | Kai Spiegelhalder 1 Correspondence Dieter Riemann, Department of Clinical Summary Psychology and Psychophysiology, Centre for Progress in the field of insomnia since 2017 necessitated this update of the Mental Disorders, Medical Centre – University of Freiburg, Faculty of Medicine, University of European Insomnia Guideline. Recommendations for the diagnostic procedure for Freiburg, Germany; Hauptstr. 5, D-79104 insomnia and its comorbidities are: clinical interview (encompassing sleep and medi- Freiburg, Germany. Email: [email protected] cal history); the use of sleep questionnaires and diaries (and physical examination and additional measures where indicated) (A). Actigraphy is not recommended for the routine evaluation of insomnia (C), but may be useful for differential-diagnostic pur- poses (A). Polysomnography should be used to evaluate other sleep disorders if sus- pected (i.e. periodic limb movement disorder, sleep-related breathing disorders, etc.), treatment-resistant insomnia (A) and for other indications (B). Cognitive-behavioural therapy for insomnia is recommended as the first-line treatment for chronic insomnia in adults of any age (including patients with comorbidities), either applied in-person or digitally (A). When cognitive-behavioural therapy for insomnia is not sufficiently For affiliations refer to page 26 This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2023 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society. J Sleep Res. 2023;32:e14035. wileyonlinelibrary.com/journal/jsr 1 of 36 https://doi.org/10.1111/jsr.14035  13652869, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jsr.14035 by CochraneItalia, Wiley Online Library on [28/10/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 2 of 36 RIEMANN ET AL. effective, a pharmacological intervention can be offered (A). Benzodiazepines (A), benzodiazepine receptor agonists (A), daridorexant (A) and low-dose sedating antide- pressants (B) can be used for the short-term treatment of insomnia (≤ 4 weeks). Longer-term treatment with these substances may be initiated in some cases, consid- ering advantages and disadvantages (B). Orexin receptor antagonists can be used for periods of up to 3 months or longer in some cases (A). Prolonged-release melatonin can be used for up to 3 months in patients ≥ 55 years (B). Antihistaminergic drugs, antipsychotics, fast-release melatonin, ramelteon and phytotherapeutics are not recommended for insomnia treatment (A). Light therapy and exercise interventions may be useful as adjunct therapies to cognitive-behavioural therapy for insomnia (B). KEYWORDS diagnosis, evidence-based medicine, guideline, insomnia, treatment 1 | SUMMARY FOR PATIENTS 1.3 | Who developed this guideline? 1.1 | What is insomnia? This European Insomnia Guideline 2023 was developed by a group of researchers and clinicians in the European Sleep Research Society Insomnia is a sleep disorder where people struggle to get off to sleep (ESRS), and the European Insomnia Network (EIN). or to stay asleep. Some individuals have both issues, and others may also have early-morning awakenings, where they are unable to get back to sleep after awakening earlier than desired. Importantly, these 1.4 | Which treatment is recommended by this night-time sleep difficulties are coupled with significant daytime prob- guideline? lems that affect the person's ability to function at their best. Daytime fatigue, low mood or irritability, and problems with attention or con- It is recommended that all patients with insomnia, whether they have centration are usually experienced. To be diagnosed with an “insom- other medical conditions or mental health problems, or not, are offered nia disorder”, these difficulties have to occur at least several times a CBT-I as their initial treatment. CBT-I may be delivered by a clinician or week over a period of 3 months. Insomnia is a very common disorder therapist (F2F), or (preferably guided) digitally using a scientifically dem- (up to 10% of the adult population in Europe) and, in addition to a onstrated web or mobile treatment platform. If this approach is not suf- great deal of personal suffering, it also results in increased costs to ficiently effective, it is recommended that patients and their treating healthcare services and to society at large (e.g. reduced productivity physicians should come to a shared decision about whether or not med- at work). ication might be initiated. At present, the evidence suggests that drug treatments in general should be limited to, at most, 4 weeks in duration, and even then with care: tolerance develops within days to weeks. Dose 1.2 | How can insomnia be treated? increases are not advised, and may accelerate the development of dependence. In some cases, longer treatment periods may be indicated, Currently, there are two ways to treat insomnia. According to scien- carefully weighing the advantages and disadvantages. tific evidence the first, and the most effective, approach is cognitive- behavioural therapy for insomnia (CBT-I). As the name suggests, CBT-I addresses the mental or cognitive aspects of insomnia (e.g. the 2 | GUIDELINE REPORT racing mind), and the behavioural aspect reestablishes a healthy sleep pattern. CBT-I can be offered as single or group therapy (face-to-face This guideline is an update of the European Insomnia Guideline that [F2F]) or as a digital therapy, where it is delivered as a web-based was published in 2017 (Riemann, Baum, et al., 2017), and developed intervention or on a treatment-based app. The second approach to by a task force of the ESRS and the EIN. The European Insomnia treat insomnia is pharmacological (i.e. pill-based). There is a variety of Guideline was based on the German Insomnia Guideline (Riemann, sleep medications available, but it is recommended that these are only Baglioni, et al., 2017) and was endorsed by the World Sleep Society taken for a short period (no longer than 4 weeks) to avoid the body (Morin et al., 2021). A revision of the German Insomnia Guideline is getting used to them or becoming dependent upon them. In some underway (Spiegelhalder et al., 2023). This first update of the cases, after weighing the advantages and disadvantages, some medi- European Insomnia Guideline is inspired by and draws upon this revi- cations may be given for longer periods of time. sion of the German Insomnia Guideline.  13652869, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jsr.14035 by CochraneItalia, Wiley Online Library on [28/10/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License RIEMANN ET AL. 3 of 36 This guideline focuses on the target population of adult patients For the area of non-pharmacological treatments, the suffering from chronic insomnia as defined by the International Classi- keyword “insomnia” was searched in connection with fication of Diseases (ICD-10/ICD-11). This includes all subtypes of other keywords: “sleep hygiene”, “relaxation”, “mind- insomnia, for example, non-organic insomnia/chronic insomnia and fulness”, “behavior therapy”, “cognitive therapy”, “cog- insomnia comorbid with somatic (formerly named “organic” insomnia) nitive behavioral therapy”, “stimulus control”, “sleep or mental disorders. The guideline addresses adult patients over the restriction”, “psychotherapy”, “light therapy”, “exer- age of 18 years. The literature on insomnia in children and adoles- cise”, “music”, “non-invasive brain stimulation”. cents was not reviewed. The guideline is based on a review of all relevant international lit- For the area of pharmacological treatments, the key- erature and has a particular salience to the provision of clinical ser- word “insomnia” was searched in connection with vices across Europe. It will be of interest to health professionals who other keywords: “benzodiazepine”, “benzodiazepine are involved in the diagnosis and treatment of insomnia on either an receptor agonist”, “sedating antidepressant”, “antipsy- out- or in-patient basis. Most insomnia is managed by general practi- chotic”, “neuroleptic”, “orexin”, “antihistaminic”, tioners in primary care settings, and by clinicians who are not special- “herbal”, “phytotherapy”, “melatonin”. ists in sleep medicine. The guideline should also be helpful to such individuals (i.e. who treat insomnia in routine clinical care without Furthermore, the journal Sleep Medicine Reviews was hand access to advanced expertise or facilities). The guideline should also searched for meta-analyses on the diagnosis and treatment of insom- be useful to specialists in psychiatry, clinical psychology/psychother- nia. All issues of this journal until October 2022 were incorporated, apy, psychosomatic medicine, neurology, occupational medicine, phar- furthermore articles were incorporated that were “in press”. macy/pharmacology and other medical specialties who commonly see patients with insomnia in the context of other comorbid physical and mental health conditions. Finally, the guideline will be especially rele- 2.2 | Writing and consensus vant to professionals trained in sleep medicine and who are members of, or are credentialled by, the ESRS. The first draft of this update was formulated and written by Dieter The revised guideline highlights aspects of clinical management Riemann and Kai Spiegelhalder, following partly, and where adequate, that reflect advances in knowledge and practice that can be delin- the update of the German insomnia guideline (Spiegelhalder eated from the updated evidence. Accordingly, less emphasis is placed et al., 2023). In the next step, all involved authors received the first upon detailed reproduction of extant information that is already out- draft of the guideline (15 April 2023) and were asked to provide feed- lined in the 2017 version (Riemann, Baglioni, et al., 2017). back within a period of 4 weeks (15 May 2023). After receiving feedback and incorporating suggested changes/improvements in the second draft of the guideline, two online meetings were held on 2.1 | Literature search 21 July and 1 August 2023 to discuss this version of the guideline and to reach consensus. A third draft of the guideline was then sent out The 2023 update was designed to build upon scientific knowledge asking for final consent from all authors by 7 August 2023. Finally, the and clinical recommendations from the first guideline, which covered guideline was approved by the guideline committee of the ESRS and evidence up to June 2016 (Riemann, Baglioni, et al., 2017; Riemann, by the ESRS board, before submission to Journal of Sleep Baum, et al., 2017). This strategy therefore aimed to both complement Research (JSR). and extend previous literature searches, while applying a consistent methodology. Therefore, to identify relevant studies on the topic of insomnia, a 2.3 | Grading of the evidence/recommendations systematic literature search (English language articles only) was con- ducted using the databases Pubmed and Cochrane Library (www. In order to grade the evidence of included studies/meta-analyses to cochranelibrary.com) for the period from June 2016 until October update the recommendations in the guideline, a procedure similar 2022 (with a further update till May 2023 added). For this update, pri- to that already outlined in 2017 (Lorenz et al., 2001; Riemann, marily meta-analyses were identified as the basis for grading recom- Baglioni, et al., 2017; Riemann, Baum, et al., 2017) was followed mendations. If there were several meta-analyses on a given topic, the (Table 1). most recent and qualitatively better meta-analyses were chosen to be The transformation of grades of evidence into grades of recom- presented in the first instance. The quality of meta-analyses was mendations was performed according to this scheme and through judged by methodological rigour, like low risk of bias, number of consensus decision between all involved authors. For more details, included studies or sample sizes. For topics without published see supplemental material in Riemann, Baum, et al. (2017). Instead of meta-analyses, systematic reviews or qualitatively adequate random- only using two types of recommendations (strong versus weak; Rie- ised controlled studies were used. mann, Baum, et al., 2017), we used four steps of recommendations for The following keywords were used for literature search: this update, ranging from A (very strong recommendation), B (strong),  13652869, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jsr.14035 by CochraneItalia, Wiley Online Library on [28/10/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 4 of 36 RIEMANN ET AL. C (weak) to D (very weak recommendation). Please note; levels of evi- T A B L E 2 Diagnostic criteria for chronic insomnia disorder dence do not always directly translate into grades of recommendation, according to ICSD-3 (AASM, 2014) as suggested in Table 1; in some cases, a consensus decision became A. The patient reports, or the patient's parent or caregiver observes, the decisive factor for the grading of the recommendation. one or more of the following: Reported effect sizes from the meta-analyses were graded as fol- 1. Difficulty initiating sleep lows: effect sizes (Cohen's D) ≥ 0.2– < 0.5: small effect; effect sizes 2. Difficulty maintaining sleep ≥ 0.5– < 0.8: medium effect; effect sizes ≥ 0.8: large effect. 3. Waking up earlier than desired 4. Resistance to going to bed on appropriate schedule 5. Difficulty sleeping without parent or caregiver intervention 3 | D I A G NO S I S O F I N S O M N I A B. The patient reports, or the patient's parent or caregiver observes, one or more of the following related to the nighttime sleep The 2017 version of this guideline reflected upon marked advances in difficulty: understanding insomnia as a disorder in its own right (insomnia disor- 1. Fatigue/malaise der), that had been recommended by the DSM-5 (Diagnostic and Sta- 2. Attention, concentration or memory impairment tistical Manual of The American Psychiatric Association; APA, 2013) 3. Impaired social, family, occupational or academic performance and the third edition of ICSD-3 (International Classification of Sleep 4. Mood disturbance/irritability Disorders; AASM, 2014). Practicing clinicians in most European coun- 5. Daytime sleepiness tries, however, generally have to adhere to the International Classifi- 6. Behavioural problems (e.g. hyperactivity, impulsivity, aggression) cation of Diseases (ICD: World Health Organisation). It is noteworthy, 7. Reduced motivation/energy/initiative therefore, that the latest revision (ICD-11) was endorsed by the 8. Proneness for errors/accidents World Health Assembly at its 72nd meeting in 2019 and came into 9. Concerns about or dissatisfaction with sleep effect globally on 1 January 2022 (WHO, 2022). Whereas the previ- C. The reported sleep/wake complaints cannot be explained purely ous version (ICD-10; WHO, 1994) differentiated “non-organic” versus by inadequate opportunity (i.e. enough time is allotted for sleep) or “organic insomnia”, this distinction was abandoned as not evidence inadequate circumstances (i.e. the environment is safe, dark, quiet based in ICD-11 in favour of the comprehensive category “chronic and comfortable) for sleep insomnia” (Code 7A00; and “short-term insomnia” for “transient D. The sleep disturbance and associated daytime symptoms occur at insomnia”). Criteria for insomnia disorder according to DSM-5, least three times per week ICSD-3 and ICD-11 are now broadly aligned, and are depicted in E. The sleep disturbance and associated daytime symptoms have Tables 2 and 3. been present for at least 3 months F.The sleep/wake difficulty is not better explained by another sleep disorder T A B L E 1 Study types, hierarchy of evidence and grades of recommendation Level of Grade of T A B L E 3 Diagnostic criteria for chronic insomnia according to Type of study evidence recommendation ICD-11 (Code 7A00) Systematic review/meta-analysis of 1a A RCTs (https://icd.who.int/browse11/l-m/en#/http://id.who.int/icd/entity/ 323148092) One high-quality RCT 1b A Chronic insomnia is a frequent and persistent difficulty initiating or “All or nothing principle” 1c B maintaining sleep that occurs despite adequate opportunity and Systematic review of high-quality 2a B circumstances for sleep, and that results in general sleep cohort studies dissatisfaction and some form of daytime impairment. Daytime One cohort study/RCT with 2b B symptoms typically include fatigue, depressed mood or irritability, adequate design but moderate general malaise, and cognitive impairment. The sleep disturbance data quality and associated daytime symptoms occur at least several times per week for at least 3 months. Some individuals with chronic insomnia Outcome research studies 2c B may show a more episodic course, with recurrent episodes of One systematic review of case 3a B sleep/wake difficulties lasting several weeks at a time over several control studies years. Individuals who report sleep-related symptoms in the One case control study 3b B absence of daytime impairment are not regarded as having an insomnia disorder. If the insomnia is due to another sleep–wake Case series/cohort or case control 4 C disorder, a mental disorder, another medical condition, or a studies of moderate quality substance or medication, chronic insomnia should only be Expert opinion, etc. 5 D diagnosed if the insomnia is an independent focus of clinical attention. Abbreviation: RCT, randomised–controlled study.  13652869, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jsr.14035 by CochraneItalia, Wiley Online Library on [28/10/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License RIEMANN ET AL. 5 of 36 In this update we will not comment on aetiological and/or patho- clinical consideration of whether or not these sleep symptoms are physiological concepts of insomnia, as this would go far beyond the coupled with dissatisfaction with sleep and any attributed daytime remit of this guideline. The interested reader is referred to recent impairment is mandatory, as well as that symptoms occur despite ade- work, much of which is part of the special insomnia issue of JSR quate time allotted for sleep and the opportunity to sleep in a com- (Dressle & Riemann, 2023; Espie, 2023; Fernandez & Perlis, 2023; fortable environment. Quantitative criteria related to sleep-onset Palagini et al., 2023; Reffi et al., 2023; Riemann et al., 2022; Tang latency, sleep duration or the frequency of nocturnal awakenings do et al., 2023; van Someren, 2021). not have to be fulfilled in order to diagnose insomnia disorder. The An overview of the relevant diagnostic procedures is given in complaint of insomnia occurring at least three nights per week for Table 4. 3 months with associated daytime sequelae represents minimal cri- teria for this clinical evaluation of chronic insomnia disorder. 3.1 | Insomnia complaint 3.2 | Sleep diaries and questionnaires The diagnosis of chronic insomnia disorder according to DSM 5, ICSD-3 and ICD-11 continues to be solely based on taking a clinical As recognised in the 2017 guideline (Riemann, Baglioni, et al., 2017), history (anamnesis) and the patient's self-reports of sleep-onset or the evaluation of insomnia should be supported by the use of a sleep sleep maintenance difficulties, or early-morning awakening. Likewise, diary for a period of at least 7–14 days (see consensus sleep diary: Carney et al., 2012). The Insomnia Severity Index (ISI; Bastien et al., 2001) is an established tool to gauge the severity of the insom- T A B L E 4 Diagnostic management of insomnia with or without comorbidities nia. The ISI can range with a score from 0 to 28. Values from 8 to 14 suggest subclinical insomnia, values from 15 to 21 moderately General anamnesis and examination (A) severe insomnia, and values from 22 to 28 severe insomnia. The Former and present somatic, neurological and mental disorders authors recommend a cut-off score of 10 for caseness in community Personality factors, work and partnership situation, interpersonal settings, and a change score of 8.4 as a sign of moderate improvement conflicts (Morin et al., 2011). The ISI has a two-item version that can be used Substance use (medication, alcohol, caffeine, nicotine, illegal drugs) for weekly monitoring or other situations where a shorter version Physical examination (if indicated) may be needed (Kraepelien et al., 2021) The eight-item Sleep Condi- Additional measures (if indicated): laboratory testing including, e.g. tion Indicator (SCI), based upon DSM-5 criteria for insomnia disorder, blood count, thyroid, hepatic and renal parameters, C-reactive is an alternative instrument to the ISI (Espie, Kyle, Hames, protein, haemoglobin, ferritin and vitamin B12; if indicated: electrocardiogram, electroencephalogram, computed tomography/ et al., 2014). The SCI also has a two-item short-form version (Luik Magnetic resononance tomography, circadian markers (melatonin, et al., 2019), and has age and sex reference data on a sample of core body temperature) 200,000 adults (Espie et al., 2018), with a Reliable Change Index The anamnesis should include caregivers if necessary of 7 scale points. The frequently used Pittsburgh Sleep Quality Index Sleep history (A) (PSQI; Buysse et al., 1989) may be helpful to gain a broader picture of History of the sleep complaints and daytime functioning sleep-related symptoms that can be relevant for the judgement Information from bed partner/caregivers (snoring, breathing of insomnia. The PSQI delivers values from 0 to 21, with values above pauses = apneas, periodic limb movements during sleep, nocturnal 5 supposedly reflecting clinically relevant sleep impairments. It should restlessness, “strange” behaviours) be noted, however, that the PSQI is not a measure of insomnia disor- Work time/circadian factors (shift- and night work, phase advance, der, but it broadly asks about symptoms from a range of other sleep delay) disorders. Sleep–wake pattern, including daytime sleep (sleep diary, sleep In the meantime, a variety of questionnaires has become avail- questionnaires) able, not only to measure insomnia, but for many other aspects of Actigraphy other sleep disorders (the interested reader is referred to Shahid In case of clinical suspicion of irregular sleep–wake schedules or et al., 2012). A single comprehensive and validated questionnaire for circadian rhythm sleep–wake disorders (A) sleep and daytime impairment for clinical use has not been developed In case of clinical suspicion of periodic leg movements in sleep (A) yet, to our knowledge, and is urgently needed. To assess quantitative rest activity (A) and sleep parameters (C) PSG In case of clinical suspicion of comorbid sleep disorders (A) 3.3 | Actigraphy Treatment-resistant insomnia (A) In case of clinical suspicion of large discrepancy between Although the literature on actigraphy continues to expand, and its subjectively experienced and PSG-measured sleep (B) availability may become more pervasive, there is limited support for Abbreviation: PSG, polysomnography. the mandatory application of actigraphy in the routine clinical  13652869, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jsr.14035 by CochraneItalia, Wiley Online Library on [28/10/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 6 of 36 RIEMANN ET AL. evaluation and diagnosis of insomnia. Medical grade actigraphic the discrepancy between subjective and objective findings may be via devices may be used to evaluate “free living” bedtimes and sleep an altered sleep microstructure in insomnia, including an increased times, and their variability, at a rather low cost for longer periods of frequency of micro-arousals (especially in REM sleep) and increased time, and so have particular application where a circadian rhythm amounts of fast-frequency waves (in the sigma and beta-band). sleep–wake disorder is suspected (Smith et al., 2018). According to two systematic reviews, many devices based on actigraphy underesti- mate the severity of sleep disorder symptoms and overestimate sleep 3.5 | Medical evaluation duration compared with polysomnography (PSG; Kolla et al., 2016; Smith et al., 2018). Rösler et al. (2023) concluded that actigraphy was Table 5 lists a wide range of medical, mental, neurological disorders not able to differentiate patients with insomnia from good sleepers. and substances, which are implicated in this context (please note: Actigraphy may be primarily helpful in a differential-diagnosis, to iden- probably any kind of medical disease might be involved as a causative tify irregular bedtime patterns—actigraphy, however, does not deliver or contributive factor for insomnia). a valid estimation of sleep stages like the PSG. A thorough physical examination is therefore indicated in patients Further, there are numerous lifestyle products available, in the with insomnia with suspected comorbidities, to be able to exclude form of watches or similar wearable devices, that incorporate some specific medical disorders that are in need of specific treatment and form of actigraphic and/or heart rate measurement. However, the for, when necessary, treating insomnia as a comorbid condition. The validity and utility of such devices for the diagnosis of insomnia has historical and now outdated clinical perspective, that insomnia is pri- not been satisfactorily researched or demonstrated at this point in marily a symptom, was strongly challenged by evidence that chronic time (Kolla et al., 2016). It has even been suggested that using these insomnia is an independent risk factor for mental health conditions devices might have a negative impact on sleep behaviour. such as depression or anxiety disorders (Baglioni et al., 2011; Hertenstein et al., 2019). Indeed, almost any kind of mental disorder is frequently accompanied by insomnia or can contribute to a worsening 3.4 | Polysomnography (PSG) of insomnia symptoms (Table 5). Many patients with insomnia suffer comorbidly from another mental disorder, which may be stigmatised It is well established that PSG is indicated when there is clinical suspi- and therefore will not be reported spontaneously by patients. There- cion of other sleep disorders like periodic limb movement disorder fore, within the context of the clinical evaluation of insomnia, any kind (PLMD) or any kind of sleep-related breathing disorders (SRBD; of mental disorder should be actively explored. Crönlein et al., 2012), such as obstructive sleep apnea (OSA). Because Insomnia is highly prevalent in such neurological disorders as insomnia does not protect against, or exclude, such disorders, PSG is stroke, Parkinson's disease, epilepsy, headache/migraine and trau- equally indicated if clinical suspicion is present in people with insom- matic brain injury (Bassetti et al., 2015, 2020). More recently, insom- nia. However, PSG is not necessary or sufficient for the diagnosis of nia has also been shown to represent an independent risk factor for insomnia per se (Dikeos et al., 2023). A meta-analysis of the PSG liter- some neurological disorders such as stroke and dementia (Damsgard ature in insomnia showed that, as compared with controls without et al., 2022; Zheng et al., 2019). sleep complaints, patients with insomnia have a significant reduction Insomnia is highly prevalant also in medical disorders including in sleep efficiency, a reduction in total sleep time, an increase in noc- diabetes (LeBlanc et al., 2018) and cardiovascular disease/ turnal wake times, and reductions in slow-wave sleep and rapid eye hypertension (Li, Gan, et al., 2021; Li, Li, et al., 2021; Sofi et al., 2014). movement (REM) sleep (Baglioni et al., 2014). These differences com- Indeed, it seems there is a truly bi-directional relationship between pared with good sleepers, however, are considerably lower than sleep disturbances and health conditions, such that insomnia should would be expected from subjective (i.e. sleep diaries/questionnaires) be evaluated and actively treated in comorbid conditions. Moreover, measures of sleep. Moreover, similar deviations can be found in sev- this underscores medical and psychiatric evaluations being part of a eral other sleep disorders and other conditions, resulting in insuffi- thorough insomnia assessment. Accordingly, normal sleep is recog- cient specificity. Although it has been suggested that feedback about nised as an important predictor of brain and mental health (Bassetti any discrepancy between physiological and objective and subjective et al., 2015). measures might be used therapeutically (Tang & Harvey, 2006), CBT-I Special note must be made of other sleep disorders, like SRBD/ and all other treatments are substantially effective for insomnia disor- OSA, restless legs syndrome (RLS) and PLMD. Only recently has it der in the absence of such data. We recommend that PSG should also become evident that there is a considerable percentage of patients be performed in patients with insomnia who have been refractory to with OSA also presenting with insomnia—now termed COMISA various therapeutic interventions (CBT-I and/or hypnotics) with the (comorbid insomnia and sleep apnea). Recent meta-analyses indicate aim to detect hitherto occult sleep disorders, in patients at risk for that 30%–40% of patients with insomnia may have OSA, and tiredness/fatigue-related accidents (i.e. professional drivers, etc.: to 30%–50% of patients with OSA meet insomnia criteria (Zhang, Ren, gauge the extent of sleep deprivation) and in patients where a huge Zhou, et al., 2019; Sweetman et al., 2021). These data argue for a mismatch between subjective and objective findings is suspected. strict inclusion of an OSA screening tool (e.g. STOP-Bang question- Riemann et al. (2022) have outlined that a potential explanation for naire; Chung et al., 2008) in the diagnostic process for insomnia and  13652869, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jsr.14035 by CochraneItalia, Wiley Online Library on [28/10/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License RIEMANN ET AL. 7 of 36 TABLE 5 Major medical comorbidities or contributory factors to chronic insomnia Mental Medical Neurological Substance use/dependence Depressive disorders Cardiovascular disorders Neurodegenerative diseases Alcohol Bipolar disorders Diabetes mellitus Cerebrovascular diseases Nicotine Anxiety disorders Chronic kidney diseases Traumatic brain injury Caffeine Borderline personality disorder Chronic obstructive pulmonary diseases Multiple sclerosis Tetrahydrocannabinol /marihuana Posttraumatic stress disorder Rheumatic disorders RLS/PLMD Opioids Schizophrenia Chronic pain Fatal familial insomnia “Designer” drugs Substance use disorders Any kind of malignant disorder Cocaine SRBD/OSA Amphetamines Abbreviations: OSA, obstructive sleep apnea; PLMD, periodic limb movement disorder; RLS, restless legs syndrome; SRBD, sleep-related breathing disorder. conversely insomnia screening for each patient with suspected psychophysiological arousal and behavioural changes like excessive SRBD. If the screening questionnaire is positive for OSA, a home time in bed. Insofar, these clinical phenomena also may need to be sleep apnea test or PSG is required for a valid diagnosis of OSA. addressed as part of the therapeutic approach towards comorbid Insomnia is a crucial symptom of many patients with RLS. PLMD insomnias. extremely frequently accompanies RLS and may contribute indepen- Please note that with DSM-5, ICSD-3 and ICD-11, comorbidity of dently to the experience of insomnia. To determine the extent to insomnia with any kind of medical disorder is acknowledged—the for- which PLMD/RLS may be contributing to the insomnia, the Interna- mer hierarchy of primary versus secondary insomnia was abandoned tional Restless Legs Syndrome Study Group Rating Scale (IRLSGR; because it lacked sufficient evidence, especially the assumed direct Abetz et al., 2006) should be used to gauge the occurrence and causality between medical disorders and associated insomnia symp- severity of symptoms. The diagnosis of RLS is mainly a clinical diag- toms, which should disappear when the primary disorder is treated, nosis, but PLMD requires a PSG. never became evidence-based. Given the high comorbidity between insomnia complaints and In summary, the diagnostic and differential-diagnostic process for OSA/SRBD, PLMD and RLS, the diagnostic and differential-diagnostic chronic insomnia disorder is complex and may require not only a clini- process should pay utmost attention to delineate the probable bi- cian's direct time, but also the involvement of medical tests and inter- directional relationships between insomnia and the “other” sleep disciplinary collaborations between different medical specialties. The disorder—this information should also directly inform the therapeutic process is not made easier due to the intricate bi-directional relation- process, meaning that in many cases the insomnia and the “other” ships between insomnia and almost any kind of medical disorder. sleep disorder will be treated simultaneously according to suggested Comorbidity may be more the rule than the exception, which entails guidelines/articles (Garcia-Borreguero et al., 2016; Sweetman the integration of insomnia treatments under a very broad medical et al., 2023). context. Furthermore, a number of substances may lead to the develop- Needless to say, a proper diagnostic and differential diagnostic ment, maintenance or aggravation of insomnia. evaluation has to take place prior to any therapy, be it CBT-I, digital Alcohol consumption may play a prominent role in this context CBT-I (dCBT-I) or any kind of pharmacological treatment. (Perney & Lehert, 2018; Hu et al., 2020; Hertenstein et al., 2019). Frequently, alcohol is also used mal-adaptively as self-medication to self-manage sleep-onset or sleep maintenance problems. Therefore, 4 | T R E A T M E N T OF I N S O M N I A alcohol consumption and other substances should be specifically probed. Insomnia as a possible side-effect of prescribed medications Up to 2016/2017, published insomnia guidelines tended to favour may occur with a huge variety of substances, including corticoste- pharmacotherapy over non-pharmacological approaches. Both fields roids, beta-blockers, beta-sympathomimetics, antibiotics, antidemen- existed in parallel worlds (i.e. on the one hand medical specialists tives, selective serotonin reuptake blockers and probably many more favouring pharmacotherapy, and on the other hand, mainly clinical (for an overview, see Riemann & Nissen, 2012; Schierenbeck psychologists and psychotherapists, favouring CBT-I or other forms of et al., 2008) impacting on sleep. psychotherapy). This antagonism seems to have been reconciled over It is important to know even in clear cases of the causative/ the last decade (see guidelines/summaries by Quaseem et al., 2016; maintaining role of a medical or mental disorder or consumption of a Wilson et al., 2019; Edinger et al., 2021), and is reflected by the wide given substance, the typical psychophysiological vicious circle of authorship of this guideline. insomnia may have developed in many patients. This includes antici- One crucial question when discussing insomnia therapy is the patory anxiety of a poor night, nocturnal ruminations, increased question who and how many patients with insomnia seek help from  13652869, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jsr.14035 by CochraneItalia, Wiley Online Library on [28/10/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 8 of 36 RIEMANN ET AL. professional healthcare. Data from Germany (Marschall et al., 2017; model of sleep regulation; Borbély, 1982). Importantly, psychoeduca- data from health insurance) indicate that probably not more than 30% tion is usually integrated into elements of CBT-I rather than being of those afflicted with insomnia have ever sought medical help. standalone information. For example, the two-process model can be Considering over the last 12 months, only 15% indicated having seen used to explain to patients that “bad nights” are often followed by a doctor specifically because of their insomnia. These sobering data “good nights” due to sleep homeostasis, serving to reinforce the ratio- need to be borne in mind when considering the treatment recommen- nale for sleep restriction and SCT. dations of this guideline. Given the bi-directional relationships Sleep hygiene: These recommendations (first presented by between insomnia and all medical disorders, a strong case can be Hauri, 1991) are also reinforced in CBT-I, and comprise advice on bed- made to raise not only public awareness but also of the medical com- room factors (e.g. temperature, light and noise levels, bed comfort) munity concerning insomnia. and habits (e.g. caffeine, alcohol, establishing a regular routine, stop Concerning the choice of treatment option, we strongly suggest clock-watching) that can impact on sleep. It should be noted, however, to follow a shared decision-making approach (Bomhof-Roordink that sleep hygiene on its own does not constitute an evidence-based et al., 2019). Diagnostic and treatment options should be outlined by treatment for insomnia, and sleep hygiene behaviours sometimes have the clinician and discussed together with the patient. a function of “safety behaviours” in patients with insomnia, heighten- ing the perceived threat of not being able to sleep. Recently the “five principles of good sleep health” have been pro- 4.1 | Non-pharmacological treatments posed, and these may form a useful introduction to the cognitive- behavioural approach (Espie, 2022b). 4.1.1 | Cognitive-behavioural therapy for insomnia (CBT-I) Relaxation therapy Many of the earliest insomnia studies included some form of relaxa- The CBT-I is typically provided as a multicomponent treatment com- tion intervention to facilitate de-arousal (Baglioni et al., 2022). This prising psychoeducation (including sleep hygiene), relaxation therapy, was consistent with the widespread adoption, in behavioural psycho- sleep-restriction therapy (SRT), stimulus control therapy (SCT) and therapy, of relaxation as a re-conditioning agent. Empirical research several cognitive therapeutic strategies. These are administered over on insomnia suggests that abbreviated progressive muscle relaxation, four–eight therapy sessions in single or group format by certified autogenic training and imagery exercises are most frequently used for health professionals (mainly clinical psychologists/psychological or the treatment of insomnia. At present there is no evidence that one medical psychotherapists). Baglioni et al. (2022) summarised these or the other method is superior, but the range of possibilities provides treatments in a comprehensive manual/textbook aimed at health pro- a multitude of treatment options. fessionals involved in the treatment of insomnia. Chapter 2 in this book (pp. 19–41) describes the CBT-I “standard protocol”, and pro- Sleep-restriction therapy (SRT) vides detailed information on the scientific basis, therapy rationale The behavioural model of insomnia put forth by Spielman et al. (1987) and treatment instructions for each CBT-I component (Espie, 2022a). identified time in bed extension as important in the maintenance of Baglioni, Altena, et al. (2020), have summarised CBT-I training strate- insomnia. Extending time in bed (including napping), often as a com- gies and the dissemination of CBT-I to health professionals. The web- pensatory response to poor sleep, can lead to increased sleep laten- site of the ESRS lists presently available teaching courses for health cies, sleep fragmentation, and increased variability in the timing of the professionals in Europe (www.esrs.eu). sleep–wake pattern. SRT aims to restrict sleep opportunity and har- The multicomponent delivery approach is typical of the pattern ness increased sleep pressure to consolidate sleep and regularise its of CBT provision in other common disorders, such as anxiety and occurrence (Spielman et al., 1987). Once sleep is consolidated depression. That said, substantial early evidence was gathered on (indexed by sleep efficiency thresholds of > 85% or 90%), the goal is single component treatments for insomnia (e.g. progressive relaxa- to extend time in bed, often on a weekly basis, to arrive at a sleep tion, stimulus control, paradoxical intention, sleep restriction), and opportunity that delivers nightly sleep need, improved sleep continu- there has been a return to evaluating separate components in recent ity, and optimised daytime functioning. There is, however, variation in years. This is in keeping with broader moves to “deconstruct” multi- the configuration of SRT in relation to defining the initial time in bed modal approaches, generate evidence on specific therapeutics, prescription, minimum time in bed (e.g. 4.5, 5 or 6 hr), position of the understand mechanisms of action, and the growth in personalised sleep window, and weekly titration parameters (Kyle et al., 2015). SRT medicine. is hypothesised to work through restricting, regularising and recondi- tioning sleep opportunity, which drives a cascade in cognitive, beha- Psychoeducation/sleep hygiene vioural and physiological pathways to improve sleep and daytime Psychoeducation: This typically comprises foundational information functioning (Maurer et al., 2018; Spielman et al., 1987). Evidence from on the roles and functions of sleep, age-related changes, and how randomised–controlled trials (RCTs) shows that acute implementation sleep–wake (circadian) patterns are regulated (e.g. the two-process of SRT increases sleepiness proximal to bedtime, decreases pre-sleep  13652869, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jsr.14035 by CochraneItalia, Wiley Online Library on [28/10/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License RIEMANN ET AL. 9 of 36 TABLE 6 Meta-analyses on the efficacy of CBT-I in chronic insomnia/insomnia disorder without comorbidities No. Effects on study Author (year) Population studies/patients Intervention Study endpoints endpoints Morin et al. (1994) Insomnia 59/2102 CBT-I and single SOL, WASO, NOA, TST (a) Good effects of CBT-I components on all parameters (b) Good follow-up results Murtagh and Insomnia 66/2007 CBT-I and single SOL, NOA, TST, SQ (a) Good effects of CBT-I Greenwood (1995) components on all parameters (b) Good follow-up results Pallesen et al. (1998) Insomnia, 13/388 CBT-I and single SOL, NOA, WASO, TST (a) Good effects of CBT-I age > 50 years components on all parameters (b) Good follow-up results Montgomery and Primary insomnia, 7/322 CBT-I, bright light SOL, TST, SE, WASO (a) Good effects of CBT-I Dennis (2004) age > 60 years and physical on sleep maintenance exercise (b) Almost no effects of bright light and physical exercise Irwin et al. (2006) Insomnia, 23/NA CBT-I and single SQ, SOL, TST, SE, WASO Medium to strong effects age > 55 years components in older patients versus younger patients Okajima et al. (2011) Primary insomnia 14/927 CBT-I SOL, WASO, EMA, SE, (a) Good effects of CBT-I PSG, ACT on all parameters (b) Good follow-up results Miller et al. (2014) Primary insomnia 4/192 SRT SOL, WASO, TST, NOA, Sleep restriction alone is SE, SQ effective Koffel et al. (2015) Insomnia 8/659 Group CBT-I SOL, WASO, SE, SQ, TST, Group CBT-I is effective pain, depression Trauer et al. (2015) Chronic insomnia 20/1162 CBT-I SOL, WASO, TST, SE Clinically relevant efficacy without undesired side- effects Ballesio et al. (2018) Insomnia 47/4317 CBT-I Depression, fatigue Small effects for depression, no significant effects for fatigue Chung et al. (2018) Insomnia 15/1194 Psychoeducation/ ISI, SE, TST, SOL, WASO, Psychoeducation/sleep sleep hygiene AKT, PSQI hygiene less effective versus CBT-I than CBT-I for PSQI, ISI, SE, SOL, WASO (medium to large ES) Mitchell et al. (2019) Insomnia disorder 15/1541 CBT-I PSG, ACT Small effects on actigraphy, no effects on PSG parameters Van der Zweerde, van Insomnia 30/2835 CBT-I SE, SOL, ISI 3, 6 and Small to medium ES for Straten, et al. 12 months after ISI and SE, small ES for (2019) therapy SOL at follow-ups Benz et al. (2020) Insomnia disorder 86/15,578 CBT-I Daytime impairments in Small to medium ES for the context of insomnia depression, anxiety, fatigue, quality of life and daytime functioning Thakral et al. (2020) Insomnia 16/1964 CBT-I Dysfunctional thoughts Large ES for and beliefs about sleep dysfunctional thoughts and beliefs about sleep post-treatment and at follow-up (Continues)  13652869, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jsr.14035 by CochraneItalia, Wiley Online Library on [28/10/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 10 of 36 RIEMANN ET AL. TABLE 6 (Continued) No. Effects on study Author (year) Population studies/patients Intervention Study endpoints endpoints Ballesio et al. (2021) Insomnia 15/1058 CBT-I Repetitive negative Small ES for worry, no thinking (e.g. significant effect for ruminations) rumination Edinger et al. (2021) Chronic insomnia 89/not indicated CBT-I and its TST, SE, SOL, WASO, SQ, Medium to large ES for single ISI, PSQI sleep parameters, components smaller ES for single components Kwon et al. (2021) Insomnia > 60 years 28/2391 CBT-I, BT, PSQI All treatments effective acupuncture against waitlist Maurer, Schneider, Insomnia 8/533 Sleep restriction TST, SE, SOL, WASO, ISI Large effects on SE, et al. (2021) WASO, ISI; medium effects on SOL; no effect on TST Xu et al. (2021) Insomnia 31/2449 F2F CBT-I TST, SE, SOL, WASO, Significant effects for ISI, NOA, ISI, PSQI, PSQI, TST, SE, SOL, depression, anxiety, WASO, NOA, fatigue, somatic and depression and fatigue; mental health no significant effects on anxiety and mental health Yu et al. (2021) Insomnia 14/2263 CBT-I TST, SE, SOL, depression, Significant effects for anxiety TST, SE, SOL, depression and anxiety Alimoradi et al. (2022) Insomnia 24/1977 CBT-I Quality of life Small to medium effects on quality of life Huang, Li, et al. (2022) Insomnia > 60 years 14/792 CBT-I TST, SE, SOL, WASO Significant effects for TST, SE, SOL, WASO Jansson-Fröjmark Insomnia 10/384 Paradoxical TST, SE, SOL, NOA Large ES for SOL, NOA, et al. (2022) intention medium ES for TST, no effect for SE Kwon et al. (2022) Insomnia 10/496 Brief behavioural TST, SE, SOL, WASO Significant effects for SE, therapy SOL, WASO 1– 8 weeks after therapy Abbreviations: ACT, actigraphy; BT, behavior therapy; CBT-I, cognitive-behavioural therapy for insomnia; EMA, early-morning awakening; ES, effect size; F2F, face-to-face; ISI, Insomnia Severity Index; NOA, number of awakenings; PSG, polysomnography; PSQI, Pittsburgh Sleep Quality Index; SE, sleep efficiency; SOL, sleep-onset latency; SQ, sleep quality; SRT, sleep-restriction therapy; TST, total sleep time; WASO, wake time after sleep onset. arousal, and improves markers of sleep continuity and sleep depth Cognitive therapeutics (Maurer, Schneider et al., 2022). Difficulties with cognitive arousal, mental events intruding upon sleep, heightened emotion and counterproductive sleep effort are very com- Stimulus control therapy (SCT) mon in insomnia. Over the past few decades, numerous cognitive The basic concept in stimulus control is that many patients with techniques have been developed and tested to address these prob- insomnia exhibit a learned association between the bed/bedroom and lems. In most trials, and in routine clinical practice, these are com- being awake (instead of sleeping). Bootzin (1972) conceived of SCT as monly “bundled” within the “C” component of CBT-I. The an operant conditioning paradigm; we go to bed to get the reward of interventions themselves are described in detail elsewhere (Baglioni sleep. There is heavily reinforced instrumental learning in good et al., 2022; Espie, 2022a). In brief, they are cognitive control (“putting sleepers because of the regular proximal relationship between bed the day to rest” before going to bed), paradoxical intention (abandon- and (rapid) sleep onset. However, this connection is broken in insom- ing effort to sleep/attempting to remain awake), imagery training nia and counterproductive classical conditioning can occur. SCT com- (active visualisation exercises that capture attention and manage rumi- prises seven primary instructions with the aim of eliminating these nation) and cognitive restructuring (challenging negative thoughts by maladaptive connections and reestablishing the connection where means of Socratic dialogue or within the framework of behavioural “bed” again equals “sleep” to the patient. experiments).  13652869, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jsr.14035 by CochraneItalia, Wiley Online Library on [28/10/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License RIEMANN ET AL. 11 of 36 The evidence-base: CBT-I for insomnia without comorbidities The evidence-base: CBT-I for insomnia with comorbidities Meta-analyses concerning CBT-I are depicted in Table 6. The CBT-I is also effective when insomnia is comorbid with other Up to now, 25 meta-analyses have been published focusing on medical disorders (Table 7). the effect of CBT-I on insomnia/insomnia disorder in those without There have been 15 published meta-analyses concerning CBT-I comorbidities since 1994. It should be critically mentioned that many for insomnia when comorbid with other conditions since 2011. early studies used a waitlist group as a control group, which is not as In the area of mental disorders, medium to large effects have powerful as a placebo group, typically used in pharmacological studies. been reported on insomnia severity when insomnia is comorbid with Furthermore, these meta-analyses are not independent of each other, depression, posttraumatic stress disorder or alcohol dependency thus there may be overlap within the studies. These issues, therefore, (Hertenstein et al., 2022). There is not sufficient evidence concerning may overemphasise the effects of CBT-I. That said, a number of early insomnia comorbid with bipolar disorders (Bisdounis et al., 2022) or placebo-controlled studies with small sample sizes (Espie et al., 1989; psychotic disorders (Hertenstein et al., 2022). CBT-I is also effective Turner & Ascher, 1979) exist, and suggested positive effects of CBT-I when insomnia is comorbid with tinnitus (Curtis et al., 2021), chronic beyond sham comparison groups. pain (Selvanathan et al., 2021), cancer (Gao, Liu, et al., 2022; Squires Most recent meta-analyses on the efficacy of CBT-I in insomnia/ et al., 2022), sleep apnea (COMISA; Sweetman et al., 2023), and in insomnia disorder, without comorbidities, show large effects on the patients with neurological disorders such as traumatic brain injury, severity of insomnia symptoms (see summary by Edinger et al., 2021), stroke or Parkinson's disease (Ford et al., 2023; Lebrun et al., 2020). whereby follow-up measurements up to a year later show small to Interestingly, especially in the area of mental disorders, the evidence medium effects (van der Zweerde, Bisdounis, et al., 2019). indicates that CBT-I not only has sleep-related effects, but also has a positive effect on the symptoms of the comorbid disorder/condition The evidence-base: CBT-I component-related efficacy (Hertenstein et al., 2022). In relation to the monotherapy of insomnia, from the active elements of CBT-I, data up to now suggest efficacy of SRT (Edinger et al., 2021; The evidence-base: CBT-I in self-help formats or delivered digitally Kyle et al., 2023; Maurer, Schneider, et al., 2021), SCT (Edinger Over the past 10 years there has been a growing literature on the et al., 2021), relaxation therapy (Edinger et al., 2021) and paradoxical application of CBT-I in self-help formats, particularly using either self- intention as one specific cognitive therapeutic (Jansson-Fröjmark help books/texts or, now, dCBT-I. To date, 11 meta-analyses are avail- et al., 2022). Psychoeducation/sleep hygiene alone does not appear to able on this topic (Table 8). A meta-analysis by Gao, Ge, et al. (2022), be very effective (Chung et al., 2018; Edinger et al., 2021), probably explored a range of delivery formats, and reported that CBT-I in single because many patients are already aware of these recommendations therapy, in group therapy and in digital form, with or without support (Lacks & Rotert, 1986). Thus, sleep hygiene advice given alone is not by therapists, is effective. Single therapy, group therapy and digital recommended in the treatment of chronic insomnia disorder and, in therapy with personal support were most effective (Gao, Ge, RCTs among patients with insomnia, sleep hygiene is often used as et al., 2022). A further recent meta-analysis by Hasan et al. (2022) also the “placebo” condition (Bjorvatn et al., 2011). suggests that personal support is to be preferred when CBT-I is A network meta-analysis (Steinmetz et al., 2022, 2023) that aimed administered digitally. to delineate the efficacy of the different components of CBT-I Interestingly, the most contemporary network meta-analysis on showed that sleep restriction and stimulus control seem to be the all forms of CBT-I administrations (i.e. onsite versus digital and other most effective components of CBT-I. Nevertheless, interventions settings; Simon, Steinmetz, et al., 2023) demonstrated that individual based on single strategies should be offered in full consideration of F2F CBT-I, group F2F CBT-I, telehealth (videoconference, phone call) motivational and safety issues. Especially the behavioural strategies and guided bibliotherapy conveyed the strongest effects on insomnia, because sleep restriction and stimulus control may be very challenging whereas guided and unguided dCBT-I yielded medium effect sizes, for the patients; thus, the intervention may require careful consider- slightly favouring guided over unguided dCBT-I. Smart phone applied ation of the patient's motivation and readiness to apply the strategy CBT-I did not attain significant effects compared with control. with systematic regularity. Furthermore, these therapeutics may tem- In Europe, several dCBT-I treatment programs are now available porarily increase daytime sleepiness and fatigue in the early interven- in web and/or mobile application format. Table 9 presents information tional phases, thus safety issues should be fully discussed with the on these programs, their evidence base, and levels of adoption. patient. To obtain this information, all members of the EIN (n = 250) and all authors of this guideline (n = 44) were asked to complete a ques- The evidence-base: CBT-I effects beyond sleep complaints tionnaire about digital tools available in their home country, which Importantly, beyond beneficial effects on sleep-related outcomes, resulted in the above-mentioned tables. The evidence base reported CBT-I also has positive effects on associated subclinical depressive reflects publications available from peer-review journals. For a sys- symptoms, anxiety, daytime sleepiness and fatigue (Benz et al., 2020), tematic overview encompassing the wider number of apps claiming to dysfunctional cognitions related to sleep (Thakral et al., 2020), worry improve sleep that are available through App stores, see Simon, Reim- (Ballesio et al., 2021), and quality of life (Alimoradi et al., 2022). ann, et al. (2023).  13652869, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jsr.14035 by CochraneItalia, Wiley Online Library on [28/10/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 12 of 36 RIEMANN ET AL. TABLE 7 Meta-analyses on the efficacy of CBT-I on insomnia/insomnia disorder with comorbidities No. Author (year) Population studies/patients Intervention Study endpoints Effects on study endpoints Belleville et al. Insomnia with/without 50/2690 CBT-I Anxiety scales Moderate effects on anxiety (2011) comorbid anxiety Geiger-Brown Comorbid insomnia 23/1379 CBT-I SOL, WASO, TST, SE, ISI, Good efficacy; long-term et al. (2015) (somatic/mental) PSQI effects at 18 months Wu et al. (2015) Comorbid insomnia 37/2189 CBT-I SOL, WASO, SQ, TST, Good efficacy; smaller effects (somatic/mental) remission, comorbid on comorbid symptoms; symptoms better effects for mental outcomes Ho et al. (2016) Insomnia + PTSD 11/593 CBT-I SOL, WASO, SE, TST, PTSD Good sleep effects, good symptoms effects on PTSD symptoms Johnson et al. Insomnia + cancer 8/752 CBT-I SE, WASO, ISI, cancer Good sleep effects, good (2016) symptoms effects on cancer symptoms Tang et al. Insomnia + pain 11/1066 CBT-I SQ, fatigue, pain Good sleep effects, good (2015) effects on comorbid symptoms Van Straten Insomnia, with and 87/6303 CBT-I SE, SOL, ISI Significant medium to large et al. (2018) without comorbidities ES for SE, SOL, ISI Feng et al. Insomnia disorder + 17/1756 CBT-I ISI, PSQI, depressive Significant ES for ISI/PSQI, (2020) depression symptoms weaker effects for depressive symptoms Zhou Insomnia disorder + 13/853 CBT-I SOL, WASO, SQ, ISI Medium ES for ISI, SQ; et al., 2020 psychiatric/somatic weaker effects for SOL, comorbidity WASO Curtis et al. Insomnia + tinnitus 4/470 CBT-I ISI Medium ES for ISI (2021) Ma et al. (2021) Insomnia disorder + 14/1363 CBT-I ISI Medium ES for ISI breast cancer Selvanathan Insomnia + chronic pain 12/762 CBT-I Global sleep parameters, pain, Strong ES for global sleep et al. (2021) depressive symptoms parameters, smaller ES for pain and depressive symptoms Gao, Liu, et al. Insomnia + cancer 16/1523 CBT-I SE, SOL, WASO, ISI Small to medium ES for ISI, (2022) SOL, WASO Hertenstein Insomnia + comorbid 22/1083 CBT-I ISI, comorbid symptom Significant medium to large et al. (2022) mental disorders severity ES for ISI, significant ES for symptoms of comorbid disorder Squires et al. Insomnia + cancer 22/1461 CBT-I ISI, TST, SE, SOL, WASO, SQ, Medium ES for ISI, small to (2022) anxiety, depressive large ES for TST, SE, SOL, symptoms, fatigue, quality WASO, SQ, anxiety, of life depressive symptoms, fatigue, quality of life Abbreviations: CBT-I, cognitive-behavioural therapy for insomnia; ES, effect size; ISI, Insomnia Severity Index; PSQI, Pittsburgh Sleep Quality Index; PTSD, posttraumatic stress disorder; SE, sleep efficiency; SOL, sleep-onset latency; SQ, sleep quality; TST, total sleep time; WASO, wake time after sleep onset. Table 9 summarises dCBT-I treatments where effectiveness for progress. Almost half of the evidence-based dCBT-I programs are insomnia is supported through at least one pre-registered published now reimbursed by the local/national health authorities, and can be randomised–controlled trial (RCT). As described in the table, some recommended or prescribed at the cost of local health insurance. Slee- programs incorporate guidance from health professionals whilst pio from the UK (also available in the USA) is the most extensively others are fully automated. Guidance means participants are offered researched dCBT-I application, having generated 13 published RCTs support (either by mail or phone) to discuss critical issues and including a placebo-controlled trial.  13652869, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jsr.14035 by CochraneItalia, Wiley Online Library on [28/10/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License RIEMANN ET AL. 13 of 36 TABLE 8 Meta-analyses on the efficacy of self-help/digital CBT-I for insomnia No. Author (year) Population studies/patients Intervention Study endpoints Effects on study endpoints Van Straten and Insomnia 10/1000 Self-help CBT-I SOL, WASO, SE, SQ, Small to moderate effects Cuijpers (2009) TST Cheng and Dizon Insomnia 6/433 dCBT-I SOL, WASO, SE, SQ, Small to moderate effects (2012) TST Ho et al. (2015) Insomnia 20/2411 Self-help + dCBT-I SOL, WASO, SE, SQ, Self-help CBT-I is effective and TST acceptable as a starter for treatment Ye et al. (2015) Insomnia with 9/776 dCBT-I Anxiety, depression Moderate effect sizes for comorbid comorbid symptoms conditions Zachariae et al. Insomnia 11/1460 dCBT-I ISI, SOL, WASO, Comparable to F2F CBT-I (2016) NOA, TST, SQ Seyffert et al. (2016) Insomnia 15/2392 dCBT-I ISI, SOL, TST, WASO, Good efficacy for sleep NOA, SQ, PSQI parameters, good follow-up results Soh et al. (2020) Insomnia 33/9364 dCBT-I ISI, other sleep Small ES for ISI parameters Ho et al. (2020) Insomnia + 30/5945 Self-help CBT-I Insomnia symptoms, Medium ES for insomnia depression depressive symptoms, smaller ES for symptoms depressive symptoms Gao, Ge, et al. Insomnia 61/11,571 CBT-I in several TST, SE, SOL, WASO, Significant effects of individual (2022) formats including ISI and group CBT-I and dCBT-I dCBT-I with or without assistance; largest for individual and group CBT-I and dCBT-I with assistance Hasan et al. (2022) Insomnia 54/11,815 dCBT-I TST, SE, SOL, WASO Significant effects of assisted dCBT-I for TST, SE, SOL, WASO Forma et al. (2022) Chronic insomnia 20/5659 dCBT-I SOL, WASO, ISI Significant effects for ISI, WASO Abbreviations: CBT-I, cognitive-behavioural therapy for insomnia; dCBT-I, digital-cognitive behavioural therapy for insomnia; ES, effect size; F2F, face-to- face; ISI, Insomnia Severity Index; NOA, number of awakenings; PSQI, Pittsburgh Sleep Quality Index; SE, sleep efficiency; SOL, sleep-onset latency; SQ, sleep quality; TST, total sleep time; WASO, wake time after sleep onset. Table S1 (supplemental material) summarises programs which, up that this type of therapy has to undergo rigorous quality control as to now, lack evidence through an RCT. Some of these programs have well (e.g. does it really contain all important ingredients of CBT-I?) and also been tested in uncontrolled single-arm trials. is it evidence-based, meaning has it been subjected to at least one To summarise, at present there is a rapidly developing market of high-quality RCT? Gold-standard evidence criteria for the regulation digital health applications targeting the treatment of insomnia, with of dCBT-I (digital therapeutics) have been published (Espie, Torous, & some of the applications already having a considerable database and Brennan, 2022; Table 10). Importantly, developers should be aware being reimbursed by local health authorities. Concerning RCT sup- that an evidence-informed intervention (broadly based on CBT-I but ported applications (Table 9), five European languages (including not specifically subjected to trials) is not an adequate substitute for Dutch, English, French, German and Swedish) are already covered. being evidence based (Espie, Firth, & Torous, 2022). This development definitely reflects the overall trend for digitalisation We also stress that local health authorities in the various in healthcare, but may also be seen as a consequence of our previous European countries should take over this regulatory function—in guideline (Riemann, Baglioni, et al., 2017; Riemann, Baum, Germany and the UK, for example, the same authority that regu- et al., 2017), in which we recommended CBT-I as first-line treatment lates medications has embraced this task. Future research will have for insomnia. Digital CBT-I surely will make access to CBT-I easier to demonstrate whether digital CBT-I is really equivalent to in-per- than before (particularly when fully automated and 24/7 available), son/F2F therapy and to which degree increased rates of dropouts/ meeting the needs of many patients with insomnia who have no attrition may occur, especially in cases of comorbid insomnia. Cau- access to CBT-I therapists. In any case, at present, it must be stressed tion is urged in cases of comorbid insomnia, especially when severe  13652869, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jsr.14035 by CochraneItalia, Wiley Online Library on [28/10/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wil