Cognitive behavioral therapy for insomnia to treat major depressive disorder with comorbid insomnia: A systematic review and meta-analysis.

OBJECTIVE: Cognitive behavioral therapy for insomnia (CBT-I) has demonstrated efficacy for both insomnia and depression. With a tenfold increase in expected participant numbers, we aimed to update the systematic review and meta-analysis of CBT-I for major depressive disorders (MDD). METHODS: Multiple databases were searched up to March 27th 2024 to include all randomized controlled trials examining CBT-I among adults with MDD. The certainty of evidence was evaluated using GRADE. The primary outcome was depression response at post-treatment. Secondary outcomes included insomnia remission and all-cause dropout at post-treatment. Frequentist random-effects pairwise meta-analyses were performed using odds ratio (OR) for dichotomous outcomes. This study was prospectively registered (https://osf.io/kcndz/). RESULTS: Nineteen trials with 4808 randomized participants were identified (mean age, 33.2 [standardized deviation 15.0] years, 73.2 % women. Mean Insomnia Severity Index 19.2 [5.4], median Patient Health Questionnaire-9 16 [range, 8-21]). CBT-I was more beneficial than control conditions for depression response (OR 2.28 [95 % Confidence Interval (CI), 1.67-3.12; GRADE certainty of evidence: moderate), insomnia remission (OR 3.57 [95%CI, 2.48-5.14]: moderate) but could lead to more dropout (OR 1.69 [95%CI, 0.98-2.89]: low). Depression improvement was seen beyond the sleep domain. With a control condition depression response rate of 17 % at post-treatment (median 8 weeks), CBT-I yielded a 32 % response rate (95 % CI, 26 %-39 %). CONCLUSIONS: This meta-analysis indicates that CBT-I has significant effects on depressive symptoms beyond the sleep domain among people with MDD. Despite higher dropout rates, these findings suggest CBT-I is an effective treatment for depression comorbid with insomnia.

Identifying mechanistic links between sleep disturbance and binge eating: the role of depressed mood.

Global sleep disturbance is robustly linked with a subjective sense of loss-of-control over eating (LOC). Depressed mood has been proposed as a mechanism to explain the bi-directional relationship between sleep disturbance and LOC eating. The current study evaluated whether sleep disturbance indirectly affects LOC eating via depressed mood. Adults seeking treatment for a DSM-5 binge-spectrum eating disorder (e.g. bulimia nervosa, binge-eating disorder) were recruited (n = 79) and asked to complete self-report questionnaires assessing sleep disturbance and depression, and a semi-structured interview assessing LOC eating. Tests of indirect effects evaluated the effect of depressed mood on the association between global sleep disturbance and LOC frequency covarying for BMI and parent study. A significant indirect effect of depressed mood on the association between global sleep disturbance and frequency of LOC eating was identified (Est = 1.519, S.E. = 0.859, p = .033). The indirect effect of depressed mood on the association between sleep disturbance and LOC eating may indicate that depressed mood serves as a mechanistic link between sleep disturbance and LOC eating. The findings offer preliminary support for adjunctive treatments targeting both sleep disturbance and depressed mood for LOC eating. Future research should explore these pathways in a larger clinical sample.

Initial treatment choices for long-term remission of chronic insomnia disorder in adults: a systematic review and network meta-analysis.

BACKGROUND: We aimed to evaluate the comparative efficacy and acceptability of cognitive behavioral therapy for insomnia (CBT-I), pharmacotherapy, and their combination in the long and short terms among adults with chronic insomnia disorder. METHODS: We searched multiple databases to December 27, 2023. We included trials in hypnotic-free adults with chronic insomnia comparing at least two of CBT-I, pharmacotherapy, or their combination. We assessed the confidence in evidence using CINeMA. The primary outcome was long-term remission. Secondary outcomes included all-cause dropout and self-reported sleep continuity measures in the long term, and the same outcomes in the short term. We performed frequentist random-effects network meta-analyses (CRD42024505519). FINDINGS: We identified 13 trials including 823 randomized participants (mean age, 47.8 years; 60% women). CBT-I was more beneficial than pharmacotherapy in the long term (median duration, 24 weeks [range, 12 to 48 weeks]; remission odds ratio, 1.82 [95% confidence interval (CI), 1.15-2.87]; [certainty of evidence: high]), while there was weaker evidence of benefit of combination against pharmacotherapy (1.71 [95% CI, 0.88-3.30: moderate]) and no clear difference of CBT-I against combination (1.07 [95% CI, 0.63-1.80: moderate]). CBT-I was associated with fewer dropouts than pharmacotherapy. Short-term outcomes favored CBT-I over pharmacotherapy except total sleep time. Given the average long-term remission rate in the pharmacotherapy-initiating arms of 28%, CBT-I resulted in a long-term remission rate of 41% (95% CI, 31%-53%) and combination 40% (95% CI, 25%-56%). INTERPRETATION: The current study found that starting with CBT-I for chronic insomnia leads to better outcomes than pharmacotherapy. Combination may be better than pharmacotherapy alone, but unlikely to be worth the additional burden over CBT-I alone.

Empirical clustering to identify individuals for whom insomnia is more closely related to suicidal ideation.

BACKGROUND: Although the effect sizes are modest, insomnia is consistently associated with suicidal thoughts and behaviors. Subgroup analyses can efficiently identify for whom insomnia is most relevant to suicidal ideation. To improve clinical case identification, the present study sought to identify subclusters of lifetime suicidal ideators for whom insomnia was most closely related to current suicidal ideation. METHODS: Data on N = 4750 lifetime suicidal ideators were extracted from the Military Suicide Research Consortium's Common Data Elements. Data on sociodemographic characteristics, severity and history of suicidal thoughts and behaviors, and related clinical characteristics were clustered by unsupervised machine learning algorithms. Robust Poisson regression estimated cluster by insomnia associations with current suicidal ideation. RESULTS: Three clusters were identified: a modest symptom severity cluster (N = 1757, 37.0 %), an elevated severity cluster (N = 1444 30.4 %), and a high severity cluster (N = 1549 32.6 %). In Cluster 1, insomnia was associated with current suicidal ideation (PRR 1.29 [1.13-1.46]) and remained significant after adjusting for sociodemographic and clinical covariates. In Cluster 2, insomnia was associated with current suicidal ideation (PRR 1.14 [1.01-1.30]), but not after adjusting for sociodemographic and clinical covariates. In Cluster 3, insomnia was associated with current suicidal ideation (PRR 1.12 [1.03-1.21]) and remained significant after adjusting for sociodemographic covariates, but not clinical covariates. LIMITATIONS: Cross-sectional design, lack of diagnostic data, non-representative sample. CONCLUSION: Insomnia appears more closely related to current suicidal ideation among modest severity individuals than other subgroups. Future work should use prospective designs and more comprehensive risk factor measures to confirm these findings.

Chronic insomnia, REM sleep instability and emotional dysregulation: A pathway to anxiety and depression?

The world-wide prevalence of insomnia disorder reaches up to 10% of the adult population. Women are more often afflicted than men, and insomnia disorder is a risk factor for somatic and mental illness, especially depression and anxiety disorders. Persistent hyperarousals at the cognitive, emotional, cortical and/or physiological levels are central to most theories regarding the pathophysiology of insomnia. Of the defining features of insomnia disorder, the discrepancy between minor objective polysomnographic alterations of sleep continuity and substantive subjective impairment in insomnia disorder remains enigmatic. Microstructural alterations, especially in rapid eye movement sleep ("rapid eye movement sleep instability"), might explain this mismatch between subjective and objective findings. As rapid eye movement sleep represents the most highly aroused brain state during sleep, it might be particularly prone to fragmentation in individuals with persistent hyperarousal. In consequence, mentation during rapid eye movement sleep may be toned more as conscious-like wake experience, reflecting pre-sleep concerns. It is suggested that this instability of rapid eye movement sleep is involved in the mismatch between subjective and objective measures of sleep in insomnia disorder. Furthermore, as rapid eye movement sleep has been linked in previous works to emotional processing, rapid eye movement sleep instability could play a central role in the close association between insomnia and depressive and anxiety disorders.

Risk for Suicide and Homicide Peaks at Night: Findings From the National Violent Death Reporting System, 35 States, 2003-2017.

Objective: The Mind after Midnight hypothesis proposes that nocturnal wakefulness increases the risk for dysregulated behaviors. Prior studies highlight a greater risk for suicide at night after adjusting for population wakefulness. How this risk varies hour to hour, differs across subgroups, or applies to other behaviors is unknown.Methods: Data on 78,647 suicides and 50,526 homicides from the National Violent Death Reporting System were combined with population wakefulness data for 2003-2017 from the American Time Use Survey. Hourly incident risk ratios (IRRs) were estimated after adjusting for population wakefulness. Two-way analysis of variances identified significant time-by-subgroup interactions that were quantified in post hoc analyses.Results: Suicide counts peaked at 12:00 PM, while homicide counts peaked at 10:00- 11:00 PM. Adjusting for demographics and population wakefulness revealed a 5-fold greater risk for suicide at 3:00 AM (aIRR: 5.20 [4.74-5.70]) and an 8-fold greater risk for homicide at 2:00 AM (aIRR: 8.04 [6.35-10.2]). Hourly risk for suicide varied by age, ethnicity, blood alcohol level, and current partner conflict. Hourly risk for homicide varied by sex and blood alcohol level.Conclusions: Risk for suicide and homicide is greater at night than expected based on the number of people awake at that time. Nighttime risk was greater among young adults and those intoxicated with alcohol, but not among those with a history of suicidal ideation or attempts. Further research should evaluate mechanisms of risk and confirm these findings at an individual level.

Move your feet and sleep: A longitudinal dynamic analysis of self-reported exercise, sedentary behavior, and insomnia symptoms.

INTRODUCTION: Insomnia symptoms are associated with poor physical and mental health. Exercise is associated with good sleep while sedentary behavior is associated with poor sleep. This study investigated the longitudinal, dynamic associations among exercise, sedentary behavior, and insomnia symptoms. METHODS: Seven hundred and fifty-six adults (Mage=47.2years, 54.9% female) took part in an online longitudinal study investigating sleep and health across the lifespan. Participants reported duration of moderate-to-strenuous exercise, percentage of day spent sitting, and insomnia symptoms (Insomnia Severity Index [ISI]). The ISI was scored as a total score and two-factor scores: (1) Sleep Disturbance (items 1, 2, 3) and (2) Daytime Dysfunction (items 4, 5, 6, 7). Multilevel modeling was used to examine the typical (i.e., between-persons) and individual (i.e., within-persons) associations among sedentary behavior, exercise, and insomnia symptoms. RESULTS: Sedentary behavior was significantly associated with total ISI scores at both the between-person and within-person levels (ß = 0.036, t = 3.23, p = .001; ß = 0.014, t = 1.99, p = .048). Both between-persons and within-person levels of sedentary behavior were associated with Daytime Dysfunction (ß = 0.028, t = 3.79, p < .001; ß = 0.009, t = 2.08, p = .039). Exercise was associated with total ISI and Daytime Dysfunction scores at the between-persons level but not at the within-persons level (ß = 0.028, t = 2.57, p = .01; ß = -0.002, t = -3.02, p = .003). CONCLUSIONS: Sedentary behavior was a more consistent and robust predictor of insomnia symptoms than exercise. The association between sedentary behavior and insomnia symptoms was dynamic in that when an individual reported being more sedentary than their norm, they also reported more insomnia symptoms. Future analyses should examine potential moderator variables and comorbid conditions.

The natural history of insomnia: evaluating illness severity from acute to chronic insomnia; is the first the worst?

STUDY OBJECTIVES: The 3P and 4P models represent illness severity over the course of insomnia disorder. The 3P model suggests that illness severity is worst during acute onset. The 4P model suggests that illness severity crescendos with chronicity. The present analysis from an archival dataset assesses illness severity with new onset illness (i.e. from good sleep [GS] to acute insomnia [AI] to chronic insomnia [CI]). Illness severity is quantified in terms of total wake time (TWT). METHODS: GSs (N = 934) were followed up to 1 year with digital sleep diaries, and classified as GS, AI, or CI. Data for CIs were anchored to the first of 14 days with insomnia so that day-to-day TWT was represented prior to and following AI onset. A similar graphic (+/-acute onset) was constructed for number of days per week with insomnia. GS data were temporally matched to CI data. Segmented linear mixed regression models were applied to examine the change in slopes in the AI-to-CI period compared to GS-to-AI period. RESULTS: Twenty-three individuals transitioned to AI and then CI. Average TWT rose during the first 2 weeks of AI onset (b = 1.8, SE = 0.57, p = 0.001) and was then stable for 3 months (b = -0.02, SE = 0.04, p = 0.53). Average number of affected days was stable from AI to CI (b = 0.0005, SE = 0.002, p = 0.81). That is, while there was week-to-week variability in the number of days affected, no linear trend was evident. CONCLUSIONS: In our sample of CIs, primarily with middle insomnia, the average severity and number of affected days were worst with the onset of AI (worst is first) and stable thereafter.

Components and Delivery Formats of Cognitive Behavioral Therapy for Chronic Insomnia in Adults: A Systematic Review and Component Network Meta-Analysis.

Importance: Chronic insomnia disorder is highly prevalent, disabling, and costly. Cognitive behavioral therapy for insomnia (CBT-I), comprising various educational, cognitive, and behavioral strategies delivered in various formats, is the recommended first-line treatment, but the effect of each component and delivery method remains unclear. Objective: To examine the association of each component and delivery format of CBT-I with outcomes. Data Sources: PubMed, Cochrane Central Register of Controlled Trials, PsycInfo, and International Clinical Trials Registry Platform from database inception to July 21, 2023. Study Selection: Published randomized clinical trials comparing any form of CBT-I against another or a control condition for chronic insomnia disorder in adults aged 18 years and older. Insomnia both with and without comorbidities was included. Concomitant treatments were allowed if equally distributed among arms. Data Extraction and Synthesis: Two independent reviewers identified components, extracted data, and assessed trial quality. Random-effects component network meta-analyses were performed. Main Outcomes and Measures: The primary outcome was treatment efficacy (remission defined as reaching a satisfactory state) posttreatment. Secondary outcomes included all-cause dropout, self-reported sleep continuity, and long-term remission. Results: A total of 241 trials were identified including 31 452 participants (mean [SD] age, 45.4 [16.6] years; 21 048 of 31 452 [67%] women). Results suggested that critical components of CBT-I are cognitive restructuring (remission incremental odds ratio [iOR], 1.68; 95% CI, 1.28-2.20) third-wave components (iOR, 1.49; 95% CI, 1.10-2.03), sleep restriction (iOR, 1.49; 95% CI, 1.04-2.13), and stimulus control (iOR, 1.43; 95% CI, 1.00-2.05). Sleep hygiene education was not essential (iOR, 1.01; 95% CI, 0.77-1.32), and relaxation procedures were found to be potentially counterproductive(iOR, 0.81; 95% CI, 0.64-1.02). In-person therapist-led programs were most beneficial (iOR, 1.83; 95% CI, 1.19-2.81). Cognitive restructuring, third-wave components, and in-person delivery were mainly associated with improved subjective sleep quality. Sleep restriction was associated with improved subjective sleep quality, sleep efficiency, and wake after sleep onset, and stimulus control with improved subjective sleep quality, sleep efficiency, and sleep latency. The most efficacious combination-consisting of cognitive restructuring, third wave, sleep restriction, and stimulus control in the in-person format-compared with in-person psychoeducation, was associated with an increase in the remission rate by a risk difference of 0.33 (95% CI, 0.23-0.43) and a number needed to treat of 3.0 (95% CI, 2.3-4.3), given the median observed control event rate of 0.14. Conclusions and Relevance: The findings suggest that beneficial CBT-I packages may include cognitive restructuring, third-wave components, sleep restriction, stimulus control, and in-person delivery but not relaxation. However, potential undetected interactions could undermine the conclusions. Further large-scale, well-designed trials are warranted to confirm the contribution of different treatment components in CBT-I.

Comparative short-term safety and efficacy of hypnotics: A quantitative risk-benefit analysis.

Several professional societies have provided recommendations for prescribing medications for insomnia. None has provided an integrative analysis that concurrently quantifies safety and efficacy (e.g., risk-benefit ratios). This represents an important gap for informing clinician decision-making. Accordingly, the aim of the present review is to provide such an analysis for five classes of sleep-promoting medications. Adverse event data values were extracted from the most recent FDA-approved package inserts and converted to an integer before being placebo-adjusted and standardized as a rate per 1000 (AEr). Efficacy data, pre-to-post self-reported data for active and placebo conditions were acquired from pivotal trials identified in "white papers" and systematic reviews/meta-analyses. Weighted effect sizes were calculated for subjective sleep latency, wake time after sleep onset and total sleep time, and then were averaged by medication class for each sleep continuity variable. Overall efficacy was represented by a single variable, SWT (sleep latency + wake time after sleep onset + total sleep time). Risk-benefit was represented using a simple ratio value. For safety, it was found that melatonin receptor agonists had the lowest adverse event rate (AEr = 43.1), and non-benzodiazepine benzodiazepine receptor agonists had the highest rate (AEr = 255.0). For efficacy, it was found that the pre-to-post placebo adjusted effect sizes were largest for benzodiazepines (effect size = 1.94) and smallest for melatonin receptor agonists (effect size = 0.109). For risk-benefit, histamine antagonist had the most favourable profile (risk-benefit = 69.5), while melatonin receptor agonist had the least favourable profile (risk-benefit = 395.7). Overall, the combined metric for risk-benefit suggests that treatment with a histamine antagonist is optimal and potentially represents the best first-line therapy for the medical management of insomnia.

The Assessment of Post-COVID Fatigue and Its Relationship to the Severity and Duration of Acute COVID Illness.

Emerging data suggests that COVID-19 is associated with fatigue well beyond the acute illness period. The present analysis aimed to: (1) characterize the prevalence and incidence of high fatigue at baseline and follow-up; (2) examine the impact of COVID-19 diagnosis on fatigue level following acute illness; and (3) examine the impact of acute COVID-19 symptom severity and duration on fatigue at follow-up. Subjects (n = 1417; 81.0% female; 83.3% White; X¯age = 43.6 years) completed the PROMIS-Fatigue during the initial wave of the pandemic at baseline (April-June 2020) and 9-month follow-up (January-March 2021). A generalized linear model (binomial distribution) was used to examine whether COVID-19 positivity, severity, and duration were associated with higher fatigue level at follow-up. Prevalence of high fatigue at baseline was 21.88% and 22.16% at follow-up, with 8.12% new cases at follow-up. Testing positive for COVID-19 was significantly associated with higher fatigue at follow-up. COVID-19 symptom duration and severity were significantly associated with increased fatigue at follow-up. COVID-19 symptom duration and severity during acute illness may precipitate longer-term fatigue, which could have implications for treatment planning and future research. Future studies should further evaluate the relationship between symptom severity, duration, and fatigue.

Efficacy and safety of lemborexant in subjects previously treated with placebo for 6 months in a randomized phase 3 study.

OBJECTIVE/BACKGROUND: To examine the effects of lemborexant (LEM) 5 mg (LEM5) or LEM 10 mg (LEM10) following extended placebo treatment. This post-hoc analysis used subject-reported sleep outcomes data from a phase 3 trial. PATIENTS/METHODS: The subjects in these post-hoc analyses were randomized to placebo for 6 months (Time Period [TP]1) in Study E2006-G000-303 (SUNRISE-2; NCT02952820). Following placebo exposure, subjects were re-randomized to LEM5 or LEM10 for another 6 months (TP2). Subject-reported sleep outcomes derived from sleep diaries included sleep onset latency (sSOL), wake after sleep onset (sWASO), sleep efficiency (sSE), and total sleep time (sTST). Magnitude and change rate in parameters were assessed for 7 days before/after initial randomization to placebo and 7 days before/after re-randomization to LEM (6 months later). Month 6 placebo non-responders were assessed for LEM response in TP2 using predetermined responder definitions. Safety was monitored throughout the study. RESULTS: Overall, 321 subjects received placebo; 258 re-randomized subjects received LEM5 (n = 133) and LEM10 (n = 125). Subjective sleep outcomes improved during TP1 with approximately 62 subjects (∼20%) exhibiting a sustained placebo response. Upon re-randomization to LEM, all measures showed an additional incremental benefit, most prominently in sSOL and sTST. Among Month 6 placebo non-responders, 11%-15% subsequently responded to LEM as assessed at Month 12. The safety profile was similar between treatment periods and treatment groups. CONCLUSIONS: These data suggest that even when insomnia symptoms have improved over time with placebo treatment, additional and sustained clinical gains in sleep outcomes are possible with active treatment using lemborexant.

Elevated estradiol during a hormone simulated pseudopregnancy decreases sleep and increases hypothalamic activation in female Syrian hamsters.

Sleep disruptions are a common occurrence during the peripartum period. While physical and environmental factors associated with pregnancy and newborn care account for some sleep disruptions, there is evidence that peripartum fluctuations in estrogens may independently impact sleep. However, the impact of these large fluctuations in estrogens on peripartum sleep is unclear because it is difficult to tease apart the effects of estrogens on sleep from effects associated with the growth and development of the fetus or parental care. We therefore used a hormone-simulated pseudopregnancy (HSP) in female Syrian hamsters to test the hypothesis that pregnancy-like increases in estradiol decrease sleep in the absence of other factors. Adult female Syrian hamsters were ovariectomized and given daily hormone injections that simulate estradiol levels during early pregnancy, late pregnancy, and the postpartum period. Home cage video recordings were captured at seven timepoints and videos were analyzed for actigraphy. During "late pregnancy," total sleep time and sleep efficiency were decreased in hormone-treated animals during the white light period compared to pretest levels. Likewise, during "late pregnancy," locomotion was increased in the white light period for hormone-treated animals compared to pretest levels. These changes continued into the "postpartum period" for animals who continued to receive estradiol treatment, but not for animals who were withdrawn from estradiol. At the conclusion of the experiment, animals were euthanized and cFos expression was quantified in the ventral lateral preoptic area (VLPO) and lateral hypothalamus (LH). Animals who continued to receive high levels of estradiol during the "postpartum" period had significantly more cFos in the VLPO and LH than animals who were withdrawn from hormones or vehicle controls. Together, these data suggest that increased levels of estradiol during pregnancy are associated with sleep suppression, which may be mediated by increased activation of hypothalamic nuclei.

The efficacy of intensive sleep retraining for insomnia: A systematic review and research agenda.

Intensive sleep retraining (ISR) is a brief behavioural treatment for sleep onset insomnia, administered in just a single overnight treatment session. This systematic review evaluates existing trials about the efficacy of intensive sleep retraining for treating insomnia, to inform whether there is enough evidence to recommend its use for clinical practice. A systematic literature search was conducted across three databases, yielding 108 results. Of these studies, three were deemed suitable for inclusion in this review. The included studies consistently reported significant reductions in insomnia symptoms following intensive sleep retraining, particularly decreases in sleep diary-derived sleep latency and increases in total sleep time. Based on these inconclusive but promising findings, a research agenda is proffered to test intensive sleep retraining as a treatment for insomnia. Large randomised controlled trials are needed to elucidate the potential benefits of intensive sleep retraining for different populations with insomnia, as are mechanistic trials to test which components underlie its seemingly therapeutic effects. Since more practical modalities of intensive sleep retraining administration have been developed, such trials are more feasible to conduct now than ever before.

On the relationship between EEG spectral analysis and pre-sleep cognitive arousal in insomnia disorder: towards an integrated model of cognitive and cortical arousal.

According to the hyperarousal model, insomnia is characterised by increased arousal in the cortical, cognitive, and physiological domains. However, the interaction between these arousal domains is poorly understood. The present observational case-control study aimed to investigate cortical arousal during the night, pre-sleep cognitive arousal and the relationship between these two domains. A total of 109 patients with insomnia disorder (ID) and 109 age-and gender matched healthy controls were investigated on two sleep laboratory nights. Electroencephalographic (EEG) spectral power during non-rapid eye movement (NREM) and REM sleep was analysed as a measure of cortical arousal. In addition, patients completed the Pre-Sleep Arousal Scale (PSAS), which consists of two subscales, one for cognitive arousal (PSAS-CA) and one for self-reported somatic arousal (PSAS-SA). The relationship between the subscale scores and EEG spectral power was calculated by multi- and univariate analyses of variance. During NREM and REM sleep, patients with ID showed significantly increased spectral power in the EEG gamma band. In addition, patients with ID showed significantly increased scores on both subscales of the PSAS. The PSAS-CA score was significantly associated with increased NREM and REM gamma power, whereas PSAS-SA was associated with decreases in NREM and REM gamma power. Consistent with our hypothesis, patients with ID showed increased cortical and cognitive arousal. Moreover, there was an association between these two arousal domains, which may indicate that cortical arousal during the night is (at least in part) elicited by pre-sleep worry and rumination.

Animal models of human insomnia.

Insomnia disorder (chronic sleep continuity disturbance) is a debilitating condition affecting 5%-10% of the adult population worldwide. To date, researchers have attempted to model insomnia in animals through breeding strategies that create pathologically short-sleeping individuals or with drugs and environmental contexts that directly impose sleeplessness. While these approaches have been invaluable for identifying insomnia susceptibility genes and mapping the neural networks that underpin sleep-wake regulation, they fail to capture concurrently several of the core clinical diagnostic features of insomnia disorder in humans, where sleep continuity disturbance is self-perpetuating, occurs despite adequate sleep opportunity, and is often not accompanied by significant changes in sleep duration or architecture. In the present review, we discuss these issues and then outline ways animal models can be used to develop approaches that are more ecologically valid in their recapitulation of chronic insomnia's natural aetiology and pathophysiology. Conditioning of self-generated sleep loss with these methods promises to create a better understanding of the neuroadaptations that maintain insomnia, including potentially within the infralimbic cortex, a substrate at the crossroads of threat habituation and sleep.