Search

Determining the most effective insomnia medication for patients may require therapeutic trials of different medications. In addition, medication side effects, interactions with co-administered medications, and declining therapeutic efficacy can necessitate switching between different insomnia medications or deprescribing altogether. Currently, little guidance exists regarding the safest and most effective way to transition from one medication to another. Thus, we developed evidence-based guidelines to inform clinicians regarding best practices when deprescribing or transitioning between insomnia medications. Five U.S.-based sleep experts reviewed the literature involving insomnia medication deprescribing, tapering, and switching and rated the quality of evidence. They used this evidence to generate recommendations through discussion and consensus. When switching or discontinuing insomnia medications, we recommend benzodiazepine hypnotic drugs be tapered while additional CBT-I is provided. For Z-drugs zolpidem and eszopiclone (and not zaleplon), especially when prescribed at supratherapeutic doses, tapering is recommended with a 1-2-day delay in administration of the next insomnia therapy when applicable. There is no need to taper DORAs, doxepin, and ramelteon. Lastly, off-label antidepressants and antipsychotics used to treat insomnia should be gradually reduced when discontinuing. In general, offering individuals a rationale for deprescribing or switching and involving them in the decision-making process can facilitate the change and enhance treatment success.

Study objectivesSleep disturbance is significantly associated with suicidal ideation. However, the majority of past research has examined the relationship between insomnia and suicidality. The current exploratory study examined the relationship of circadian rhythm dysregulation (eveningness, seasonality, and rhythmicity) with suicidality.MethodsWe examined the association of insomnia, eveningness, seasonality, and rhythmicity with suicidal ideation in 103 participants with depression, insomnia, and suicidality within a larger 8-week double-blinded randomized control trial primarily examining whether cautious use of zolpidem extended-release or placebo reduced suicidal ideation. All participants additionally received an open-label selective serotonin reuptake inhibitor. Methodological strengths of the current analyses included consideration of multiple sleep-wake constructs, adjustment for relevant covariates, investigation of relationships over the course of treatment, and use of both self-report measures and objective measurement with actigraphy.ResultsOver the course of treatment, self-reported eveningness and greater insomnia severity were independently correlated with greater suicidal ideation, whereas actigraphic delayed sleep timing was related to suicidal ideation at a trend level. At the end of treatment, those with greater suicidal ideation demonstrated lower actigraphic activity levels. There were no significant relationships between self-reported seasonality and actigraphic measures of sleep disturbance and suicidality.ConclusionsSelf-reported delays in sleep timing, objectively lower activity levels, and self-reported insomnia severity correlated independently with greater suicidal ideation in those with depression, insomnia, and suicidality. These exploratory findings highlight the need to consider sleep-wake constructs more broadly in those with suicidality in future research studies in order to improve more definitively both assessment and intervention efforts.Clinical trial registrationRegistry: ClinicalTrials.gov; Name: Reducing Suicidal Ideation through Insomnia Treatment; URL: https://clinicaltrials.gov/ct2/show/NCT01689909; Identifier: NCT01689909 Rumble ME, McCall MV, Dickson DA, Krystal AD, Rosenquist PB, Benca RM. An exploratory analysis of the association of circadian rhythm dysregulation and insomnia with suicidal ideation over the course of treatment in individuals with depression, insomnia, and suicidal ideation. J Clin Sleep Med. 2020;16(8):XXX-XXX.

ObjectiveThe authors sought to determine whether targeted treatment of insomnia with controlled-release zolpidem (zolpidem-CR) in suicidal adults with insomnia would provide a reduction in suicidal ideation superior to placebo.MethodsReducing Suicidal Ideation Through Insomnia Treatment was an 8-week three-site double-blind placebo-controlled parallel-group randomized controlled trial of zolpidem-CR hypnotic therapy compared with placebo, in conjunction with an open-label selective serotonin reuptake inhibitor. Participants were medication-free 18- to 65-year-olds with major depressive disorder, insomnia, and suicidal ideation. Suicidal ideation was the main outcome, measured first by the Scale for Suicide Ideation and second by the Columbia-Suicide Severity Rating Scale (C-SSRS).ResultsA total of 103 participants were randomly assigned to receive zolpidem-CR (N=51) or placebo (N=52) (64 women and 39 men; mean age=40.5 years). Zolpidem-CR had a robust anti-insomnia effect, especially in patients with the most severe insomnia symptoms. No significant treatment effect was observed on the Scale for Suicide Ideation (least squares mean estimate=-0.56, SE=0.83, 95% CI=-2.19, 1.08), but the reduction in scores was significantly positively related to improvement in insomnia after accounting for the effect of other depression symptoms. The C-SSRS indicated that zolpidem-CR had a significant treatment effect (least squares mean estimate=-0.26, SE=0.12, 95% CI=-0.50, -0.02). The advantage for zolpidem-CR in reducing suicidal ideation on the C-SSRS was greater in patients with more severe insomnia. No deaths or suicide attempts occurred.ConclusionsAlthough the results do not support the routine prescription of hypnotic medication for mitigating suicidal ideation in all depressed outpatients with insomnia, they suggest that coprescription of a hypnotic during initiation of an antidepressant may be beneficial in suicidal outpatients, especially in patients with severe insomnia.

Background: There are limited data regarding gamma-aminobutyric acid (GABA) allosteric modulator sleep-aid medications in persons with depression, insomnia, and suicidal ideation (SI). Aims: This secondary analysis examined the relationship of age to insomnia and the impact of age on the treatment of insomnia with zolpidem extended-release (zolpidem-ER) in depressed suicidal patients. A prior report found that the addition of zolpidem-ER promoted significantly superior reductions in global severity of insomnia in depressed outpatients with insomnia and SI over 8 weeks, but here we report the differences among early, middle, and late insomnia. Methods: This secondary analysis examined the three early, middle, and late insomnia items of the Hamilton Rating Scale for Depression (HRSD) and their relationship to age and responsiveness to treatment with zolpidem-ER. One hundred and three patients with major depression, SI, and insomnia received open-label serotonin reuptake inhibitors and were randomly allocated 1:1 to receive zolpidem-ER or placebo at bedtime. Results: Older age at baseline was associated with worse middle and late insomnia, but not with early insomnia. Subsequent treatment with zolpidem-ER produced superior improvement in early and middle insomnia, but not late insomnia. Conclusions: These findings are consistent with the known age-related advancement of sleep timing in the general population and depressed outpatients and with the expected effects of a short half-life GABA allosteric modulator sleep aid. By implication, prescribers of pharmacologic treatment of insomnia in depressed patients should consider an alternative to zolpidem-ER when late insomnia is a concern. Trial registration number: ClinicalTrials.gov Identifier: NCT01689909. [ABSTRACT FROM AUTHOR]

Daridorexant is approved for the treatment of insomnia at two dose levels (25 and 50 mg). Dose-efficacy and -safety response relationships were evaluated using Phase 2 and 3 data. Data (N = 2153) from one Phase 2 (daridorexant 5, 10, 25, 50 mg, placebo once daily for 1 month) and two Phase 3 studies (daridorexant 10 and 25 or 25 and 50 mg, placebo once daily for 3 months) were pooled. Dose-response analyses at 1 month of double-blind treatment were performed using a linear regression and a two-stage meta-analysis approach. Efficacy endpoints were polysomnography-derived wake after sleep onset, latency to persistent sleep (LPS), self-reported total sleep time and the Insomnia Daytime Symptoms and Impacts Questionnaire total score (only Phase 3 data for the latter). Safety endpoints were the incidence of total adverse events (AEs) and AEs corresponding to somnolence/fatigue. Dose-responses for all efficacy endpoints were significant in the observed dose range (both statistical approaches, p < 0.01). All dose-response relationships were linear except for LPS (two-stage meta-analysis) which showed a change in slope above 10 mg without reaching a plateau. No significant dose-response was observed for any AE (both approaches, p > 0.05). The incidence of AEs corresponding to somnolence/fatigue was low at all doses and, without linear assumption (two-stage meta-analysis) there was no dose-dependency (p = 0.369). The data support the use of 50 mg as the preferred daridorexant dose in patients with insomnia disorder to provide the greatest opportunity for efficacy with no increased risk for AEs, including somnolence/fatigue, compared to lower doses. • Analysis of Phase 2/3 data to evaluate the dose-response relationship of daridorexant. • Daridorexant showed a dose-response relationship on sleep and daytime functioning. • No evidence of a dose-response for adverse events, including somnolence/fatigue. • Results indicate a positive benefit-risk balance for daridorexant 25 mg and 50 mg. • Results support 50 mg as the preferred dose for insomnia disorder. [ABSTRACT FROM AUTHOR]

Background and Hypothesis Insomnia occurs frequently in the clinical course of schizophrenia. A growing literature has found associations between insomnia, suicidal ideation and behavior, and psychopathology in schizophrenia. We explored associations between sleep problems, suicidal ideation, and psychopathology in a cohort of patients with first-episode psychosis. Study Design We performed a secondary analysis of data for n = 403 subjects with data from the Recovery After an Initial Schizophrenia Episode study using regression models. Study Results The prevalence of sleep problems and suicidal ideation at baseline was 57% and 15%, respectively. After controlling for potential confounders, in the study baseline sleep problems were associated with increased odds of suicidal ideation with evidence of a dose-dependent relationship (OR = 2.25, 95% CI 1.15–4.41, P =.018). Over 24 months, sleep problems at any time point were associated with an over 3-fold increased odds of concurrent suicidal ideation (OR = 3.21, 95% CI 1.45–7.14, P =.004). Subjects with persistent sleep problems were almost 14 times more likely to endorse suicidal ideation at least once over the study than those without sleep problems (OR = 13.8, 95% CI 6.5–53.4, P <.001). Sleep problems were also a predictor of higher Positive and Negative Syndrome Scale total (β = 0.13–0.22), positive (β = 0.14–0.25), and general (β = 0.16–0.27) subscale scores at baseline and multiple follow-up visits (P <.01 for each). Conclusions Sleep problems are highly prevalent and associated with suicidal ideation and greater psychopathology in first-episode psychosis. Formal assessment and treatment of insomnia appear relevant to the clinical care of patients with psychosis as a predictor of suicidal ideation and symptom severity. [ABSTRACT FROM AUTHOR]

Background: Insomnia disorder is a highly prevalent, significant public health concern associated with substantial and growing health burden. There are limited real-world data assessing the burden of insomnia disorder on daytime functioning and its association with comorbidities. The objective of this study was to leverage large-scale, real-world data to assess the burden of untreated insomnia disorder in terms of daytime impairment and clinical outcomes. Methods: This United States medical claims database study compares patients diagnosed with insomnia disorder but not receiving treatment ('untreated insomnia' cohort) to patients without an insomnia disorder diagnosis and without treatment ('non-insomnia' cohort). International Classification of Disease, Tenth Revision codes were used as a proxy to represent the three symptom domains (Sleepiness, Alert/Cognition, Mood) of the Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ), a newly developed and validated tool used in clinical studies to assess daytime functioning in insomnia disorder. Chronic Fatigue (R53.83) and Other Fatigue (R53.83), Somnolence (R40.0) and Disorientation (R41.0) were selected as categories representing one or more IDSIQ domains. Clinical outcomes included cardiovascular events, psychiatric disorders, cognitive impairment and metabolic disorders. Results: Approximately 1 million patients were included (untreated insomnia: n = 139,959; non-insomnia: n = 836,975). Compared with the 'non-insomnia' cohort, the 'untreated insomnia' cohort was more likely to experience daytime impairments, with mean differences in occurrences per 100 patient-years for: (a) fatigue, at 27.35 (95% confidence interval [CI] 26.81, 27.77, p < 0.01); (b) dizziness, at 4.66 (95% CI 4.40, 4.90, p < 0.01); (c) somnolence, at 4.18 (95% CI 3.94, 4.43, p < 0.01); and (d) disorientation, at 0.92 (95% CI 0.77, 1.06, p < 0.01). During the 1-year look-back period, patients in the 'untreated insomnia' cohort were also more likely to have been diagnosed with arterial hypertension (40.9% vs. 26.3%), psychiatric comorbidities (40.1% vs. 13.2%), anxiety (29.2% vs. 8.5%), depression (26.1% vs. 8.1%) or obesity (21.3% vs. 11.1%) compared with those in the 'non-insomnia' cohort. Conclusions: This large-scale study confirms the substantial burden of insomnia disorder on patients in a real-world setting, with significant daytime impairment and numerous comorbidities. This reinforces the need for timely insomnia disorder diagnosis and treatments that improve both sleep, as well as daytime functioning. [ABSTRACT FROM AUTHOR]

Introduction: Little is known about the relative magnitude of placebo responses on objective and subjective measures of sleep continuity. To address this issue, the pre-post effects of placebos on objective and subjective measures (i.e., polysomnography [PSG] and sleep diaries) were evaluated meta-analytically. The guiding hypothesis was that large responses would be observed on sleep diary measures and small responses would be observed on PSG measures. Methods: PubMed searches, 1967–2016, yielded 329 possible articles, 17 of which met the inclusion and exclusion criteria for the present analysis (including 879 subjects with PSG data, 1,209 subjects with diary data, and six studies with both PSG and sleep diary data). Average change and weighted effect sizes (ESs) were computed via modeling for sleep latency (SL), wake after sleep onset (WASO) and total sleep time (TST). Results: Pre-to-post change on PSG measures were: SL −13.7 min., ES = −0.37; WASO −14.3 min., ES = −0.36; and TST 29.8 min., ES = 0.50. Pre-to-post change on sleep diary measures were: SL −13.5 min., ES = −0.36; WASO −13.3 min., ES = −0.20; and TST 25.5 min., ES = 0.36. The modeled average objective subjective difference per sleep continuity measure was less than 5 minutes. The modeled average objective subjective difference per sleep continuity measure (in effect sizes) was less than 0.17. Discussion: The observed outcomes of this analysis suggest that placebos produce comparable effects on objective and subjective measures of sleep continuity. Thus, objective measures do not appear to protect against placebo responses. This being the case and given the importance of the subjective experience of illness severity and recovery, such data suggests that prospectively sampled sleep continuity data (sleep diaries) may be the optimal data for clinical trials, particularly when only one measure is possible. [ABSTRACT FROM AUTHOR]

Insomnia is a risk factor for suicide, and both are associated with cognitive problems. However, prior research has not examined insomnia, cognition, and suicidal ideation within one sample. We describe cross‐sectional associations among insomnia, psychomotor speed, set shifting, and suicidal ideation in 85 depressed adults. Greater insomnia was associated with slower psychomotor speed, while slower psychomotor speed was associated with a greater level (i.e., elaboration of suicide planning) and intensity of suicidal ideation in the past week. Slower set shifting was associated with a greater level and intensity of suicidal ideation in the past week. Mediation analysis indicated that psychomotor speed and set shifting both had a significant total effect on the intensity of suicidal ideation in the past week; set shifting also had a significant total effect on the sum of intensity and suicidal ideation level in the past week. The level of insomnia explained only small percentages of the total effect of either psychomotor speed or set shifting on the intensity of suicidal ideation and the sum of intensity and suicidal ideation level. The findings in this sample demonstrate significant associations of slower psychomotor speed and set shifting with suicidal ideation, with negligible contribution from insomnia. [ABSTRACT FROM AUTHOR]

Background and Objective: The dual orexin receptor antagonist daridorexant, studied in two phase III trials, dose-dependently improved objective and subjective sleep variables and daytime functioning in adults with insomnia. Because treatment of insomnia in older adults is challenging and has limited options, the purpose of the current analysis was to further analyse the phase III trial studying the higher doses of daridorexant, those that showed efficacy (daridorexant 50 mg, daridorexant 25 mg and placebo, nightly for 3 months), and compare the safety and efficacy of daridorexant in patients aged ≥ 65 ('older adults') to those aged < 65 years ('younger adults'). Methods: Analyses by age (≥ 65 years, n = 364; < 65 years, n = 566) were performed on data from the randomised, double-blind, placebo-controlled Trial 1 in adult patients with insomnia (NCT03545191). Efficacy endpoints included a change from baseline at month 1 and month 3 in polysomnography-measured wake after sleep onset (WASO) and latency to persistent sleep (LPS), self-reported total sleep time (sTST) and daytime functioning assessed using the validated Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ). Safety endpoints included adverse events and the Visual Analog Scale for morning sleepiness. Results: At baseline, mean [standard deviation] WASO was numerically greater (110 [39] vs 92 [38] min) in older than younger adults, while LPS was comparable (~ 65 min). Mean baseline IDSIQ total and all domain scores were numerically lower (i.e. better) in older adults. Daridorexant caused similar reductions in WASO and LPS, and similar increases in sTST, from baseline, in both age groups; improvements were numerically greater with daridorexant 50 mg than 25 mg. At month 3, daridorexant 50 mg, compared with placebo, decreased WASO by a least-squares mean of 19.6 (95% confidence interval 9.7, 29.5) in older patients versus 17.4 min (10.7, 24.0) in younger patients and decreased LPS by a least-squares mean of 14.9 (7.5, 22.3) in older patients versus 9.7 min (3.7, 15.7) in younger patients. Daridorexant 50 mg increased sTST from baseline to month 3 by a least-squares mean of 59.9 (49.6, 70.3) in older patients versus 57.1 min (48.9, 65.3) in younger patients. Daridorexant 50 mg progressively improved IDSIQ total and domain scores from week 1 onwards similarly in both groups; daridorexant 25 mg improved IDSIQ scores, but only in younger adults. In both age groups, in comparison with placebo, the overall incidence of adverse events was comparable, and there were fewer falls on daridorexant. Daridorexant improved Visual Analog Scale morning sleepiness in both groups; daridorexant 50 mg increased the mean (standard deviation) Visual Analog Scale morning sleepiness score by 15.9 (20.7) in older adults and by 14.9 (18.7) in younger adults from baseline to month 3. In older adults, there was one case of sleep paralysis, and no cases of narcolepsy, cataplexy, or complex sleep behaviour. Conclusions: In older patients with insomnia, as in younger patients, the efficacy of daridorexant is maximal on night-time and daytime variables at the higher dose of 50 mg. Older patients particularly require this dose to improve daytime functioning. Older patients are not at an increased risk of adverse events or residual effects the next morning after night-time administration of daridorexant, even at 50 mg. The dose of daridorexant does not need to be decreased for older patients. Clinical Trial Registration: ClinicalTrials.gov (NCT03545191) [first posted: 4 June, 4 2018], https://clinicaltrials.gov/ct2/show/NCT03545191. Plain Language Summary: The burden of chronic insomnia (difficulty in falling/staying asleep or not getting enough sleep) increases with age yet treatment options in older patients are limited. In older patients, because of a risk of side effects, guidelines suggest caution when prescribing sleep medications and, for some drugs, recommend starting at a lower dose. Daridorexant was approved in 2022 for the treatment of insomnia in adults following positive results in two trials that showed daridorexant significantly improved night-time sleep and daytime functioning over 3 months of treatment in adults with insomnia. Approximately 40% of patients taking part in these trials were aged 65 years or older. This current analysis compared the safety and benefits of daridorexant in older adults (aged at least 65 years) and younger adults (aged less than 65 years) in the trial that administered the highest two doses of daridorexant, 25 and 50 mg. The results showed that the benefits of daridorexant were comparable in both age groups over 3 months; compared with placebo, daridorexant improved night-time sleep (reduced time awake during the night, reduced time to fall asleep and increased total sleep time) and daytime functioning—patients had less daytime sleepiness and a better mood and feeling of alertness. In older patients, the benefits, particularly for daytime functioning, were greatest at the higher 50-mg dose, without any increase in side effects. Both doses of daridorexant were equally well tolerated in the two age groups, indicating that treatment with daridorexant at 50 mg can be safely started in older patients. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the relationship of sleep disturbance to the antidepressant effects of esketamine. Materials and Methods: Two double-blind, 4-week studies randomized adults with treatment-resistant depression (TRD) to placebo or esketamine nasal spray, each with newly initiated antidepressant. Sleep was assessed using Montgomery–Åsberg Depression Rating Scale (MADRS) item 4. Change in response (≥ 50% decrease in MADRS total score) and remission (total MADRS score ≤ 12) at day 28 was examined by presence/absence of baseline sleep disturbance using logistic regression models. Impact on reported sleep disturbance (MADRS item 4 score) was examined using ANCOVA models. Results: At baseline, most patients reported disturbed sleep – moderate/severe (65.3%, 369/565), mild (25.3%, 143/565), or none/slightly (9.4%, 53/565) – with similar distribution between treatment groups. A higher proportion of esketamine-treated patients achieved response (OR = 2.05; 95% CI: 1.40– 3.02; P < 0.001) and remission (OR = 1.81; 95% CI: 1.23– 2.66; P = 0.003) at day 28 compared to antidepressant plus placebo, regardless of presence/severity of sleep disturbance. Consistent with this, sleep (MADRS item 4 score) improved in both groups after the first dose, more so with esketamine by day 8 (between-group difference: P ≤ 0.02 at all time points). Across both treatment groups, 1-point improvement in sleep at day 8 increased the probability of antidepressant response on day 28 by 26% (OR = 1.26, 95% CI: 1.12– 1.42; P < 0.001), and remission by 28% (OR = 1.28, 95% CI: 1.14– 1.43; P < 0.001). Conclusion: Antidepressant efficacy of esketamine was demonstrated in patients with TRD, regardless of the presence of sleep disturbance. After 8 days of treatment and thereafter, significantly more esketamine-treated patients reported improvement in sleep versus antidepressant plus placebo. [ABSTRACT FROM AUTHOR]

• There are multiple psychometric options for measuring suicidal ideation (SI), but little is known regarding how each of these options performs in a clinical trial. • The single "suicide item" within the hamilton rating scale for depression (HRSD) is a potential option for measuring SI within a clinical trial. • The HRSD suicide item was successful in discerning significant differences in SI in a clinical trial comparing zolpidem controlled CR versus placebo as add-on treatments to a selective serotonin reuptake inhibitor in outpatients with depression, insomnia, and SI. The REST-IT study found the addition of zolpidem-controlled release (CR) provided a significant reduction in observer-rated measurement of suicidal ideation (the Columbia Suicide Severity Rating Scale) in 103 depressed outpatients with insomnia and suicidal ideation, but without significant change in a self-report measure of suicidal ideation (the Scale for Suicide Ideation). This secondary analysis of the REST-IT data examined the suicide item of another observer-rated scale, the Hamilton Rating Scale for Depression (HRSD), further clarifying the impact of insomnia-focused treatment on suicidal ideation. This analysis established a significant advantage for zolpidem-CR compared with placebo on the HRSD suicide item. [ABSTRACT FROM AUTHOR]

Insomnia commonly occurs in schizophrenia, and insomnia is associated with suicide risk. Clozapine has anti-suicidal properties and beneficial effects on sleep. We performed a meta-analysis of insomnia in randomized controlled trials (RCTs) of patients with schizophrenia treated with clozapine. We hypothesized that compared to clozapine there is an increased odds of insomnia in patients treated with other antipsychotics. We systematically searched PubMed, PsycINFO, and Web of Science databases. We included RCTs, in English, with data on insomnia in patients with schizophrenia treated with clozapine versus other antipsychotics. Data were pooled using a random effects model. Eight RCTs (1952 patients: 922 on clozapine and 1030 on other antipsychotics) met inclusion criteria. Patients treated with other antipsychotics versus clozapine had a significant increased odds of insomnia (22.3 % versus 12.4 %, OR = 2.20, 95 % CI = 1.64–2.94, p < 0.01). Olanzapine, quetiapine, risperidone, and ziprasidone were each associated with significant increased odds of insomnia compared to clozapine. In meta-regression analyses, clozapine dose, publication year, sex, trial duration, and study quality score were unrelated to the association; however, there was a significant association with age. The observed ORs for insomnia from RCTs were almost perfectly correlated with reported ORs from pharmacovigilance data. Clozapine is associated with significantly less insomnia compared to other antipsychotics. Findings provide additional evidence for improvement in sleep as a potential pathway underlying clozapine's anti-suicidal properties. A greater mechanistic understanding of this association is needed. [ABSTRACT FROM AUTHOR]

Insomnia occurs frequently in the clinical course of schizophrenia. A growing literature has found associations between insomnia, suicidal ideation, and psychopathology in patients with schizophrenia. We explored these associations in a cross-sectional study of a large sample of patients with chronic schizophrenia in China. We hypothesized that insomnia would be associated with an increased odds of current suicidal ideation and higher current psychopathology scores. We recruited 328 inpatients with chronic schizophrenia, all of whom were prescribed psychotropics. We investigated relationships between current insomnia, suicidal ideation over the past two weeks, and current psychopathology for subjects using regression models. After controlling for multiple potential confounding factors, current insomnia was an indicator of a significant, 2.5-fold increased odds of suicidal ideation (OR = 2.56, 95% CI 1.10–5.95, p = 0.029). Insomnia was also a significant indicator of lifetime suicide attempt (OR = 1.07) as well as higher Positive and Negative Syndrome Scale total (β = 0.134, p = 0.017), positive (β = 0.154, p = 0.006) and general (β = 0.145, p = 0.010) subscale scores. Insomnia is associated with suicidal ideation, lifetime suicide attempt, and higher psychopathology scores in inpatients with chronic schizophrenia. Formal assessment of insomnia appears relevant to the clinical care of patients with schizophrenia as an indicator of suicidal thinking and behavior, depression, and symptom severity. • Insomnia was a significant indicator of suicidal ideation in schizophrenia. • Insomnia was a significant indicator of lifetime suicide attempt in schizophrenia. • Insomnia was associated with higher psychopathology scores in schizophrenia. • Assessment of insomnia is relevant to clinical care in schizophrenia. [ABSTRACT FROM AUTHOR]

• Terminal insomnia was significantly associated with higher IL-6 and leptin levels. • Effect sizes for IL-6 (d =1.03) and leptin (d =1.03) were large for subjects with severe (vs no) terminal insomnia. • Insomnia was not associated with levels of WBCs or CRP. • Findings are germane to trials of hypnotics and NSAIDs in schizophrenia. Insomnia and inflammation are both common in schizophrenia. In the general population, insomnia is associated with inflammation. In n=519 subjects from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial, terminal insomnia was investigated as an indicator of inflammation using non-parametric ANCOVA. After controlling for potential confounders, insomnia was significantly associated with higher blood IL-6 (F=4.12, p=0.007) and leptin (F=9.67, p<0.001) with large effect sizes (d =1.03 and d =0.79, respectively). Findings suggest that the assessment of insomnia is relevant to studies of inflammation in schizophrenia, and germane to trials of adjunctive hypnotics and anti-inflammatory agents in these patients. [ABSTRACT FROM AUTHOR]

• Insomnia is a risk factor for suicide, both in the short term and the long term. • Hopelessness mediates much of the effect of insomnia on suicide. • Some persons with insomnia experience a specific type of hopelessness as reflected in the dysfunctional beliefs and attitudes about sleep scale. • Treatment of insomnia may be a path towards mitigating suicidal ideation. [ABSTRACT FROM AUTHOR]