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Sleep Initiation and Maintenance Disorders: HELP
Articles by Ruth M. Benca
Based on 19 articles published since 2009
(Why 19 articles?)
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Between 2009 and 2019, Ruth Benca wrote the following 19 articles about Sleep Initiation and Maintenance Disorders.
 
+ Citations + Abstracts
1 Review Reconsidering Insomnia as a Disorder Rather Than Just a Symptom in Psychiatric Practice. 2018

Benca, Ruth M / Buysse, Daniel J. ·Department of Psychiatry and Human Behavior, University of California, Irvine, California, USA. · Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. ·J Clin Psychiatry · Pubmed #29370483.

ABSTRACT: ​​ Insomnia is a common feature of many psychiatric disorders but can also be a comorbid disorder, often contributing to poor outcomes and treatment failure. For some patients who do respond to psychiatric treatment, their insomnia persists after their mood symptoms have remitted, indicating that their insomnia needs to be a separate focus of treatment. In this CME Academic Highlights, Drs Ruth Benca and Daniel Buysse discuss how to effectively evaluate patients with psychiatric disorders for comorbid insomnia, as well as how to safely and effectively implement both behavioral and pharmacologic treatments. ​​​​​​​.

2 Review Hypnotic Medications and Suicide: Risk, Mechanisms, Mitigation, and the FDA. 2017

McCall, W Vaughn / Benca, Ruth M / Rosenquist, Peter B / Riley, Mary Anne / McCloud, Laryssa / Newman, Jill C / Case, Doug / Rumble, Meredith / Krystal, Andrew D. ·From the Department of Psychiatry and Health Behavior, Medical College of Georgia, Augusta University, Augusta; the Department of Psychiatry and Human Behavior, University of California, Irvine; the Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, N.C.; the Department of Psychiatry, University of Wisconsin, Madison; and the Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, N.C. ·Am J Psychiatry · Pubmed #27609243.

ABSTRACT: OBJECTIVE: Insomnia is associated with increased risk for suicide. The Food and Drug Administration (FDA) has mandated that warnings regarding suicide be included in the prescribing information for hypnotic medications. The authors conducted a review of the evidence for and against the claim that hypnotics increase the risk of suicide. METHOD: This review focused on modern, FDA-approved hypnotics, beginning with the introduction of benzodiazepines, limiting its findings to adults. PubMed and Web of Science were searched, crossing the terms "suicide" and "suicidal" with each of the modern FDA-approved hypnotics. The FDA web site was searched for postmarketing safety reviews, and the FDA was contacted with requests to provide detailed case reports for hypnotic-related suicide deaths reported through its Adverse Event Reporting System. RESULTS: Epidemiological studies show that hypnotics are associated with an increased risk for suicide. However, none of these studies adequately controlled for depression or other psychiatric disorders that may be linked with insomnia. Suicide deaths have been reported from single-agent hypnotic overdoses. A separate concern is that benzodiazepine receptor agonist hypnotics can cause parasomnias, which in rare cases may lead to suicidal ideation or suicidal behavior in persons who were not known to be suicidal. On the other hand, ongoing research is testing whether treatment of insomnia may reduce suicidality in adults with depression. CONCLUSIONS: The review findings indicate that hypnotic medications are associated with suicidal ideation. Future studies should be designed to assess whether increases in suicidality result from CNS impairments from a given hypnotic medication or whether such medication decreases suicidality because of improvements in insomnia.

3 Review Understanding the sleep-wake cycle: sleep, insomnia, and the orexin system. 2013

Krystal, Andrew D / Benca, Ruth M / Kilduff, Thomas S. · ·J Clin Psychiatry · Pubmed #24107804.

ABSTRACT: -- No abstract --

4 Review Chronic insomnia. 2012

Morin, Charles M / Benca, Ruth. ·Université Laval, Québec City, QC, Canada. cmorin@psy.ulaval.ca ·Lancet · Pubmed #22265700.

ABSTRACT: Insomnia is a prevalent complaint in clinical practice that can present independently or comorbidly with another medical or psychiatric disorder. In either case, it might need treatment of its own. Of the different therapeutic options available, benzodiazepine-receptor agonists (BzRAs) and cognitive-behavioural therapy (CBT) are supported by the best empirical evidence. BzRAs are readily available and effective in the short-term management of insomnia, but evidence of long-term efficacy is scarce and most hypnotic drugs are associated with potential adverse effects. CBT is an effective alternative for chronic insomnia. Although more time consuming than drug management, CBT produces sleep improvements that are sustained over time, and this therapy is accepted by patients. Although CBT is not readily available in most clinical settings, access and delivery can be made easier through use of innovative methods such as telephone consultations, group therapy, and self-help approaches. Combined CBT and drug treatment can optimise outcomes, although evidence to guide clinical practice on the best way to integrate these approaches is scarce.

5 Clinical Trial Suvorexant in Elderly Patients with Insomnia: Pooled Analyses of Data from Phase III Randomized Controlled Clinical Trials. 2017

Herring, W Joseph / Connor, Kathryn M / Snyder, Ellen / Snavely, Duane B / Zhang, Ying / Hutzelmann, Jill / Matzura-Wolfe, Deborah / Benca, Ruth M / Krystal, Andrew D / Walsh, James K / Lines, Christopher / Roth, Thomas / Michelson, David. ·Merck & Co., Inc., Kenilworth, NJ. Electronic address: william.herring@merck.com. · Merck & Co., Inc., Kenilworth, NJ. · Department of Psychiatry and Human Behavior, School of Medicine, University of California-Irvine, Irvine, CA. · Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC. · Sleep Medicine and Research Center, St. Luke's Hospital, St. Louis, MO. · Henry Ford Hospital Sleep Center, Detroit, MI. ·Am J Geriatr Psychiatry · Pubmed #28427826.

ABSTRACT: OBJECTIVE: Suvorexant is an orexin receptor antagonist approved for treating insomnia at doses of 10-20 mg. Previously reported phase III results showed that suvorexant was effective and well-tolerated in a combined-age population (elderly and nonelderly adults). The present analysis evaluated the clinical profile of suvorexant specifically in the elderly. METHODS: Prespecified subgroup analyses of pooled 3-month data from two (efficacy) and three (safety) randomized, double-blind, placebo-controlled, parallel-group trials. In each trial, elderly (≥65 years) patients with insomnia were randomized to suvorexant 30 mg, suvorexant 15 mg, and placebo. By design, fewer patients were randomized to 15 mg. Patient-reported and polysomnographic (subset of patients) sleep maintenance and onset endpoints were measured. RESULTS: Suvorexant 30 mg (N = 319) was effective compared with placebo (N = 318) on patient-reported and polysomnographic sleep maintenance, and onset endpoints at Night 1 (polysomnographic endpoints)/Week 1 (patient-reported endpoints), Month 1, and Month 3. Suvorexant 15 mg (N = 202 treated) was also effective across these measures, although the onset effect was less evident at later time points. The percentages of patients discontinuing because of adverse events over 3 months were 6.4% for 30 mg (N = 627 treated), 3.5% for 15 mg (N = 202 treated), and 5.5% for placebo (N = 469 treated). Somnolence was the most common adverse event (8.8% for 30 mg, 5.4% for 15 mg, 3.2% for placebo). CONCLUSION: Suvorexant generally improved sleep maintenance and onset over 3 months of nightly treatment and was well-tolerated in elderly patients with insomnia (clinicaltrials.gov; NCT01097616, NCT01097629, NCT01021813).

6 Clinical Trial Clinical profile of suvorexant for the treatment of insomnia over 3 months in women and men: subgroup analysis of pooled phase-3 data. 2017

Herring, W Joseph / Connor, Kathryn M / Snyder, Ellen / Snavely, Duane B / Zhang, Ying / Hutzelmann, Jill / Matzura-Wolfe, Deborah / Benca, Ruth M / Krystal, Andrew D / Walsh, James K / Lines, Christopher / Roth, Thomas / Michelson, David. ·Merck & Co., Inc., Kenilworth, NJ, USA. william_herring@merck.com. · Merck & Co., Inc., UG 4C-13, PO Box 1000, North Wales, PA, 19454-1099, USA. william_herring@merck.com. · Merck & Co., Inc., Kenilworth, NJ, USA. · Department of Psychiatry and Human Behavior, University of California-Irvine, Irvine, CA, USA. · Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA. · Sleep Medicine and Research Center, St., Luke's Hospital, St. Louis, MO, USA. · Henry Ford Hospital Sleep Center, Detroit, MI, USA. ·Psychopharmacology (Berl) · Pubmed #28265715.

ABSTRACT: RATIONALE: Sex-related differences in the clinical profiles of some insomnia medications have been previously reported. OBJECTIVE: To evaluate the clinical profile of suvorexant, a novel orexin receptor antagonist approved for treating insomnia at doses up to 20 mg, by sex subgroups. METHODS: Efficacy analyses by sex were based on pooled data from two similar phase 3, randomized, double-blind, placebo-controlled, 3-month trials in elderly (≥65 years) and non-elderly (18-64 years) insomnia patients. Two age-adjusted (non-elderly/elderly) dose regimes of 40/30 and 20/15 mg were evaluated, with fewer patients assigned to 20/15 mg. Efficacy was assessed by patient-reported outcomes (N = 1264 women, 707 men) and by polysomnography endpoints in ~75% of patients. Safety analyses by sex (N = 1744 women, 1065 men) included pooled data from the two 3-month trials plus 3-month data from a safety trial of 40/30 mg. RESULTS: The sex subgroup efficacy analyses mirrored the improvements seen for suvorexant 40/30 and 20/15 mg over placebo on patient-reported outcomes and polysomnography sleep maintenance and onset endpoints in the primary analyses; 95% CIs excluded zero in favor of suvorexant for most endpoints in both sexes, and similar efficacy was observed between sexes (95% CIs overlapped). Suvorexant was well-tolerated in women and men, although women in all treatment groups (including placebo) reported more adverse events than men. The most frequent adverse event was somnolence (women: 11.1% for 40/30 mg, 8.5% for 20/15 mg, 2.3% for placebo; men: 10.1% for 40/30 mg, 3.4% for 20/15 mg, 4.2% for placebo). CONCLUSION: Suvorexant was generally effective and well-tolerated in both women and men with insomnia. ClinicalTrials.gov trial registration numbers: NCT01097616, NCT01097629, NCT01021813.

7 Clinical Trial Suvorexant in Patients with Insomnia: Pooled Analyses of Three-Month Data from Phase-3 Randomized Controlled Clinical Trials. 2016

Herring, W Joseph / Connor, Kathleen M / Snyder, Ellen / Snavely, Duane B / Zhang, Ying / Hutzelmann, Jill / Matzura-Wolfe, Deborah / Benca, Ruth M / Krystal, Andrew D / Walsh, James K / Lines, Christopher / Roth, Thomas / Michelson, David. ·Merck & Co., Inc., Kenilworth, NJ. · University of Wisconsin, Madison, WI. · Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC. · Sleep Medicine and Research Center, St. Luke's Hospital, St. Louis, MO. · Henry Ford Hospital Sleep Center, Detroit, MI. ·J Clin Sleep Med · Pubmed #27397664.

ABSTRACT: STUDY OBJECTIVES: Suvorexant is an orexin receptor antagonist approved for treating insomnia at a maximum dose of 20 mg. Phase-3 trials evaluated two age-adjusted (non-elderly/elderly) dose-regimes of 40/30 mg and 20/15 mg with the primary focus on 40/30 mg. We report here results from pooled analyses of the 20/15 mg dose-regime, which was evaluated as a secondary objective in the trials. METHODS: Prespecified analysis of pooled data from two identical randomized, double-blind, placebo-controlled, parallel-group, 3-month trials in non-elderly (18-64 years) and elderly (≥ 65 years) patients with insomnia. Patients were randomized to suvorexant 20/15 mg (non-elderly/elderly), suvorexant 40/30 mg (non-elderly/elderly), or placebo; by design, fewer patients were randomized to 20/15 mg. Efficacy was assessed by self-reported and polysomnography (PSG; subset of patients) sleep maintenance and onset endpoints. RESULTS: Suvorexant 20/15 mg (N = 493 treated) was effective compared to placebo (N = 767 treated) on patient-reported and PSG sleep maintenance and onset endpoints at Night-1 (PSG endpoints) / Week-1 (subjective endpoints), Month-1 and Month-3, except for effects on PSG sleep onset at Month-3. Suvorexant 20/15 mg was generally well tolerated, with 3% of patients discontinuing due to adverse events over 3 months vs. 5.2% on placebo. Somnolence was the most common adverse event (6.7% vs. 3.3% for placebo). There was no systematic evidence of rebound or withdrawal signs or symptoms when suvorexant was discontinued after 3 months of nightly use. CONCLUSIONS: Suvorexant 20/15 mg improved sleep onset and maintenance over 3 months of nightly treatment and was generally safe and well tolerated. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov trial registration numbers: NCT01097616, NCT01097629.

8 Clinical Trial Suvorexant in Patients With Insomnia: Results From Two 3-Month Randomized Controlled Clinical Trials. 2016

Herring, W Joseph / Connor, Kathryn M / Ivgy-May, Neely / Snyder, Ellen / Liu, Ken / Snavely, Duane B / Krystal, Andrew D / Walsh, James K / Benca, Ruth M / Rosenberg, Russell / Sangal, R Bart / Budd, Kerry / Hutzelmann, Jill / Leibensperger, Heather / Froman, Samar / Lines, Christopher / Roth, Thomas / Michelson, David. ·Merck Sharp & Dohme Corporation, Whitehouse Station, New Jersey. Electronic address: william_herring@merck.com. · Merck Sharp & Dohme Corporation, Whitehouse Station, New Jersey. · Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, North Carolina. · Sleep Medicine and Research Center, St. Luke's Hospital, St. Louis, Missouri. · University of Wisconsin, Madison, Wisconsin. · Atlanta Sleep Medicine Clinic, Atlanta, Georgia. · Sleep Disorders Institute & Attention Disorders Institute, Oakland University William Beaumont School of Medicine, Sterling Heights. · Henry Ford Hospital Sleep Center, Detroit, Michigan. ·Biol Psychiatry · Pubmed #25526970.

ABSTRACT: BACKGROUND: Suvorexant is an orexin receptor antagonist for treatment of insomnia. We report results from two pivotal phase 3 trials. METHODS: Two randomized, double-blind, placebo-controlled, parallel-group, 3-month trials in nonelderly (18-64 years) and elderly (≥65 years) patients with insomnia. Suvorexant doses of 40/30 mg (nonelderly/elderly) and 20/15 mg (nonelderly/elderly) were evaluated. The primary focus was 40/30 mg, with fewer patients randomized to 20/15 mg. There was an optional 3-month double-blind extension in trial 1. Each trial included a 1-week, randomized, double-blind run-out after double-blind treatment to assess withdrawal/rebound. Efficacy was assessed at week 1, month 1, and month 3 by patient-reported subjective total sleep time and time to sleep onset and in a subset of patients at night 1, month 1, and month 3 by polysomnography end points of wakefulness after persistent sleep onset and latency to onset of persistent sleep (LPS). One thousand twenty-one patients were randomized in trial 1 and 1019 patients in trial 2. RESULTS: Suvorexant 40/30 mg was superior to placebo on all subjective and polysomnography end points at night 1/week 1, month 1, and month 3 in both trials, except for LPS at month 3 in trial 2. Suvorexant 20/15 mg was superior to placebo on subjective total sleep time and wakefulness after persistent sleep onset at night 1/week 1, month 1, and month 3 in both trials and at most individual time points for subjective time to sleep onset and LPS in each trial. Both doses of suvorexant were generally well tolerated, with <5% of patients discontinuing due to adverse events over 3 months. The results did not suggest the emergence of marked rebound or withdrawal signs or symptoms when suvorexant was discontinued. CONCLUSIONS: Suvorexant improved sleep onset and maintenance over 3 months of nightly treatment and was generally safe and well tolerated.

9 Clinical Trial Safety and efficacy of suvorexant during 1-year treatment of insomnia with subsequent abrupt treatment discontinuation: a phase 3 randomised, double-blind, placebo-controlled trial. 2014

Michelson, David / Snyder, Ellen / Paradis, Erin / Chengan-Liu, Mary / Snavely, Duane B / Hutzelmann, Jill / Walsh, James K / Krystal, Andrew D / Benca, Ruth M / Cohn, Martin / Lines, Christopher / Roth, Thomas / Herring, W Joseph. ·Merck & Co Inc, Whitehouse Station, NJ, USA. Electronic address: david_michelson@merck.com. · Merck & Co Inc, Whitehouse Station, NJ, USA. · Sleep Medicine and Research Center, St Luke's Hospital, St Louis, MO, USA. · Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA. · University of Wisconsin, Madison, WI, USA. · Omnitrials, Naples, FL, USA. · Henry Ford Hospital Sleep Center, Detroit, MI, USA. ·Lancet Neurol · Pubmed #24680372.

ABSTRACT: BACKGROUND: Suvorexant (MK-4305) is an orexin receptor antagonist shown to be efficacious for insomnia over 3 months. We aimed to assess its clinical profile during and after 1 year of treatment. METHODS: We did a randomised, placebo-controlled, parallel-group trial at 106 investigational centres in the Americas, Australia, Europe, and South Africa from December, 2009, to August, 2011. Patients aged 18 years or older with primary insomnia by DSM-IV-TR criteria were assigned using a computer-generated randomised allocation schedule to receive nightly suvorexant (40 mg for patients younger than 65 years, 30 mg for patients aged 65 years or older) or placebo at a 2:1 ratio for 1 year with a subsequent 2-month randomised discontinuation phase in which patients on suvorexant either continued suvorexant or were abruptly switched to placebo while patients on placebo remained on placebo. Treatment assignment was masked from patients and investigators. The primary objective was to assess the safety and tolerability of suvorexant for up to 1 year. Secondary objectives were to assess the efficacy of suvorexant for improving patient-reported subjective total sleep time (sTST) and time to sleep onset (sTSO) over the first month of treatment. Efficacy endpoints over the first month were assessed with a mixed model with terms for baseline value of the response variable, age, sex, region, treatment, time, and treatment by time interaction. This trial is registered with ClinicalTrials.gov, number NCT01021813. FINDINGS: 322 (62%) of 522 patients randomly assigned to receive suvorexant and 162 (63%) of 259 assigned to receive placebo completed the 1-year phase. Over 1 year, 362 (69%) of 521 patients treated with suvorexant experienced any adverse events compared with 164 (64%) of 258 treated with placebo. Serious adverse events were recorded in 27 patients (5%) who received suvorexant and 17 (7%) who received placebo. The most common adverse event, somnolence, was reported for 69 patients (13%) who received suvorexant and seven (3%) who received placebo. At month 1, suvorexant (517 patients in the efficacy population) showed greater efficacy than placebo (254 in the efficacy population) in improving sTST (38·7 min vs 16·0 min; difference 22·7, 95% CI 16·4 to 29·0; p<0·0001) and sTSO (-18·0 min vs -8·4 min, difference -9·5, -14·6 to -4·5; p=0·0002). INTERPRETATION: Our findings show that suvorexant was generally safe and well tolerated over 1 year of nightly treatment in patients with insomnia, with efficacy noted for subjective measures of sleep onset and maintenance. FUNDING: Merck & Co Inc.

10 Article Patients presenting to a Men's Health clinic are at higher risk for depression, insomnia, and sleep apnea. 2019

Walia, Arman S / Lomeli, Luis de Jesus Martinez / Jiang, Pengbo / Benca, Ruth / Yafi, Faysal A. ·Department of Urology, University of California-Irvine, Irvine, CA, USA. · Center for Complex Biological Systems, University of California-Irvine, Irvine, CA, USA. · Department of Psychiatry & Human Behavior, University of California-Irvine, Irvine, CA, USA. · Department of Urology, University of California-Irvine, Irvine, CA, USA. faysalyafi@gmail.com. ·Int J Impot Res · Pubmed #30171191.

ABSTRACT: Depression and sleep problems are highly prevalent disorders that are often comorbid with other medical disorders. We evaluated the prevalence and associations of these conditions in patients presenting to a Men's Health clinic. In this retrospective study, 124 patients presenting to a Men's Health clinic completed three urological questionnaires (International Index of Erectile Function [IIEF-5], International Prostate Symptom Score [IPSS], and Androgen Deficiency in Aging Males [ADAM]); and four non-urological questionnaires (Patient Health Questionnaire for depression [PHQ-9], STOP-BANG Sleep Apnea [OSA STOP-BANG], Insomnia Severity Index [ISI], and Epworth Sleepiness Scale [ESS]). Questionnaire results were evaluated in conjunction with patient clinical history and associated laboratory values via univariate and multivariate analysis. The mean age of the study participants was 54.1 years (SD 16). Comorbidities included hypertension (22.5%), vascular disease (15%), and diabetes mellitus (13.3%). Body Mass Index (BMI) was >25 in 77.3%. IIEF-5 scores were moderate-severe in 47.9%, ADAM questionnaire was positive in 79%, and IPSS scores were moderate-severe in 42.9% of patients. PHQ-9 demonstrated mild-severe depression in 38.6%, STOP-BANG showed intermediate-high risk for sleep apnea in 55.2%, ISI indicated moderate-severe insomnia in 18.1%, and ESS revealed mild-severe sleepiness in 16.6% of participants. On univariate analysis, BMI was associated with scores on the PHQ-9 (p = 0.035), STOP-BANG (p < 0.001), and ESS (p < 0.006). On multivariate analysis, positive ADAM questionnaire was associated with STOP-BANG (OR 3.29, 95% CI: 1.012-10.69), and IPSS with PHQ-9 (OR 4.64, 95% CI: 1.40-15.43) and ISI (OR 3.27, 95% CI: 1.06-10.1). Overall, patients presenting to a Men's Health Clinic were found to have high prevalence rates for risk of depression, insomnia and sleep apnea. Risks were elevated in older subjects, and those with increased BMI, hypogonadism, and lower urinary tract symptoms. Appropriate screening and referral to appropriate specialists are encouraged.

11 Article Assessing and Treating Insomnia in Patients With Psychiatric Disorders, Part 2. 2018

Benca, Ruth M / Buysse, Daniel J. ·Department of Psychiatry and Human Behavior, University of California, Irvine, California, USA. · Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. ·J Clin Psychiatry · Pubmed #29505189.

ABSTRACT: Tune in to this podcast as experts discuss 2 patient cases-one involving co-occurring insomnia and depression and another comprising PTSD, substance abuse, insomnia, and nightmares. Drs Benca and Buysse explain how to effectively diagnose and manage these complex cases based on the latest diagnostic criteria and evidence from clinical trials.

12 Article Assessing and Treating Insomnia in Patients With Psychiatric Disorders, Part 1. 2018

Benca, Ruth M / Buysse, Daniel J. ·Department of Psychiatry and Human Behavior, University of California, Irvine, California, USA. · Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. ·J Clin Psychiatry · Pubmed #29505188.

ABSTRACT: Listen to this podcast as experts discuss 2 patient cases focusing on diagnosing and treating co-occurring insomnia and mental illness. The first case features a 32-year-old man with bipolar disorder who is experiencing psychiatric symptoms and poor sleep, and the second case involves a 27-year-old man with schizophrenia who is having auditory hallucinations as well as chronic issues with insomnia.

13 Article Insomnia and Relationship With Immunosuppressant Therapy After Lung Transplantation. 2017

Rohde, Kalynn A / Schlei, Zachary W / Katers, Krista M / Weber, Ashley K / Brokhof, Marissa M / Hawes, Donald S / Radford, Kelly L / Francois, Mary L / Menninga, Nathan J / Cornwell, Richard / Benca, Ruth / Hayney, Mary S / Dopp, John M. ·1 Pharmacy Practice Division, School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA. · 2 University of Wisconsin Hospitals and Clinics, University of Wisconsin-Madison, Madison, WI, USA. · 3 Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA. · 4 Wisconsin Sleep Center and Department of Psychiatry, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA. ·Prog Transplant · Pubmed #28617161.

ABSTRACT: BACKGROUND: Lung transplant recipients are at high risk of developing sleep disorders such as insomnia, but the prevalence and features are currently poorly characterized within this population. Since these disorders are associated with increased morbidity and mortality, it is important to identify them to optimize the care of lung transplant recipients. We sought to evaluate the prevalence of insomnia within our university-based lung transplant clinic and determine whether a relationship exists between insomnia and exposure to immunosuppressant medications following transplantation. METHODS: Participants were recruited through the University of Wisconsin Hospital and Clinics Lung Transplant Clinic (N = 125). Participants (n = 92) completed the adult sleep history questionnaire, which included the Insomnia Severity Index (ISI) to assess for insomnia (defined as ISI score >10). Cumulative tacrolimus exposure was determined in 73 patients by performing an area under the curve calculation to assess for a potential relationship between tacrolimus exposure and insomnia. RESULTS: The prevalence of insomnia was 40% within this population. Although no difference in time since transplant was found, cumulative mean ± standard error of the mean tacrolimus exposure was significantly higher in patients with insomnia versus those without insomnia (17 190 ± 1673 ng·d/mL vs 12 130 ± 1630 ng·d/mL, respectively; P = .04). Estimated tacrolimus exposure was not greater with increasing frequency of insomnia complaints (analysis of variance P = .54). CONCLUSION: In our population, insomnia is common after lung transplantation, with prevalence greater than the general population. Higher cumulative exposure to tacrolimus may contribute to insomnia in this group. Future research should investigate the relationship between immunosuppressant therapy and development of sleep disorders.

14 Article Restless Legs Syndrome Following Lung Transplantation: Prevalence and Relationship With Tacrolimus Exposure. 2016

Menninga, Nathan J / Rohde, Kalynn A / Schlei, Zachary W / Katers, Krista M / Weber, Ashley K / Brokhof, Marissa M / Hawes, Donald S / Radford, Kelly L / Francois, Mary L / Cornwell, Richard D / Benca, Ruth / Hayney, Mary S / Dopp, John M. ·Pharmacy Practice Division, School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA. · University of Wisconsin Hospitals and Clinics, University of Wisconsin-Madison, Madison, WI, USA. · Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA. · Wisconsin Sleep Center and Department of Psychiatry, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA. · Pharmacy Practice Division, School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA john.dopp@wisc.edu. ·Prog Transplant · Pubmed #27207403.

ABSTRACT: CONTEXT: Complications following lung transplantation are common and significantly reduce quality of life, and increase morbidity and mortality. Increasing evidence suggests sleep disorders are prevalent following lung transplantation, but factors associated with their development are not known. OBJECTIVES: We sought to evaluate the prevalence of restless legs syndrome (RLS) in a lung transplant population and determine if a relationship exists between RLS and exposure to immunosuppressant medications. DESIGN, SETTING, AND PARTICIPANTS: Subjects were recruited through the University of Wisconsin Hospital and Clinics Lung Transplant Clinic (N = 125). Participants (N = 81) completed sleep questionnaires, including the four RLS diagnostic criteria, insomnia severity index, and Sheehan disability scale. Cumulative tacrolimus exposure was determined in 62 subjects by calculating an area under the curve (AUC) to assess for a relationship with restless legs syndrome. RESULTS: Prevalence of RLS was 35 percent. Cumulative mean ± SEM tacrolimus exposure was similar in patients with RLS versus those without RLS (17446 ± 1855 ng days/mL vs. 15303 ± 1643 ng days/mL, respectively; p = 0.42). Insomnia severity index scores (12.5 ± 1.0 vs 6.8 ± 0.7, p < 0.0001) and Sheehan disability scores (7.8 ± 1.3 vs 3.6 ± 0.6, p = 0.003) were significantly higher in those with vs those without RLS symptoms, respectively. CONCLUSIONS: Our data confirms increased prevalence of RLS following lung transplantation reported by previous studies. RLS symptoms were not related to estimated tacrolimus exposure. Predictors of RLS following lung transplantation need to be further investigated to better identify and control RLS symptoms and reduce associated insomnia and disability.

15 Article Regional Patterns of Elevated Alpha and High-Frequency Electroencephalographic Activity during Nonrapid Eye Movement Sleep in Chronic Insomnia: A Pilot Study. 2016

Riedner, Brady A / Goldstein, Michael R / Plante, David T / Rumble, Meredith E / Ferrarelli, Fabio / Tononi, Giulio / Benca, Ruth M. ·University of Wisconsin School of Medicine and Public Health, Department of Psychiatry, Madison, WI. · University of Arizona, Department of Psychology, Tucson, AZ. ·Sleep · Pubmed #26943465.

ABSTRACT: STUDY OBJECTIVES: To examine nonrapid eye movement (NREM) sleep in insomnia using high-density electroencephalography (EEG). METHODS: All-night sleep recordings with 256 channel high-density EEG were analyzed for 8 insomnia subjects (5 females) and 8 sex and age-matched controls without sleep complaints. Spectral analyses were conducted using unpaired t-tests and topographical differences between groups were assessed using statistical non-parametric mapping. Five minute segments of deep NREM sleep were further analyzed using sLORETA cortical source imaging. RESULTS: The initial topographic analysis of all-night NREM sleep EEG revealed that insomnia subjects had more high-frequency EEG activity (> 16 Hz) compared to good sleeping controls and that the difference between groups was widespread across the scalp. In addition, the analysis also showed that there was a more circumscribed difference in theta (4-8 Hz) and alpha (8-12 Hz) power bands between groups. When deep NREM sleep (N3) was examined separately, the high-frequency difference between groups diminished, whereas the higher regional alpha activity in insomnia subjects persisted. Source imaging analysis demonstrated that sensory and sensorimotor cortical areas consistently exhibited elevated levels of alpha activity during deep NREM sleep in insomnia subjects relative to good sleeping controls. CONCLUSIONS: These results suggest that even during the deepest stage of sleep, sensory and sensorimotor areas in insomnia subjects may still be relatively active compared to control subjects and to the rest of the sleeping brain.

16 Article Sleep Related Cognitions in Individuals with Symptoms of Insomnia and Depression. 2015

Levenson, Jessica C / Benca, Ruth M / Rumble, Meredith E. ·University of Pittsburgh School of Medicine, Pittsburgh, PA. · University of Wisconsin School of Medicine and Public Health, Madison, WI. ·J Clin Sleep Med · Pubmed #25766706.

ABSTRACT: STUDY OBJECTIVES: Depression has been identified as the most common condition comorbid to insomnia, with findings pointing to the possibility that these disorders may be causally related to each other or may share common mechanisms. Some have suggested that comorbid insomnia and depression may have a different clinical course than either condition alone, and may thus require specific treatment procedures. In this report we examined the clinical characteristics of individuals referred to an academic sleep center who report comorbid symptoms of insomnia and depression and those with symptoms of insomnia outside the context of meaningful depression, and we identified differences between these groups with regard to several cognitive-related variables. METHODS: Logistic regression analyses examined whether past week worry, dysfunctional beliefs about sleep, and insomnia symptom-focused rumination predicted group membership. RESULTS: Individuals with comorbid symptoms of insomnia and depression reported more past-week worry, dysfunctional beliefs about sleep, and insomnia symptom-focused rumination, than those with symptoms of insomnia without significant depression symptoms. When including all three cognitive-related variables in our model, those with comorbid symptoms reported more severe insomnia symptom-focused rumination, even when controlling for insomnia and mental health severity, among other relevant covariates. CONCLUSION: The findings contribute to our understanding of the complex nature of comorbid symptoms of insomnia and depression and the specific symptom burden experienced by those with significant depression symptoms in the presence of insomnia. The findings also highlight the need for increased clinical attention to the sleep-focused rumination reported by these patients.

17 Article Associations of child insomnia, sleep movement, and their persistence with mental health symptoms in childhood and adolescence. 2014

Armstrong, Jeffrey M / Ruttle, Paula L / Klein, Marjorie H / Essex, Marilyn J / Benca, Ruth M. ·Department of Psychiatry, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI. ·Sleep · Pubmed #24790268.

ABSTRACT: STUDY OBJECTIVES: To examine the patterns of insomnia and sleep-related movement from ages 4.5 to 9 years, their concurrent associations with mental health symptoms in childhood, and the longitudinal associations of sleep-problem persistence with mental health symptoms at ages 9 and 18 years. DESIGN: A 14-year prospective follow-up study. Assessments included maternal report on the Children's Sleep Habits Questionnaire at ages 4.5 and 9, and child mental health symptoms via maternal report at age 4.5, multi-informant (child, teacher, mother) report at age 9, and adolescent report at age 18. SETTING: Community. PARTICIPANTS: A total of 396 children (51% female). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Sleep problems were more common at age 4.5 than 9; symptoms of insomnia and abnormal sleep movement both had persistence rates of 9-10%. At age 4.5, insomnia was associated with hostile-aggressive and hyperactive-distractible behavior, but there were no significant associations for sleep movement. At age 9, both insomnia and sleep movement were associated with symptoms of depression, externalizing, and attention deficit hyperactivity disorder (ADHD). Insomnia persistence was associated with symptoms of depression, externalizing, and ADHD at age 9 and anxiety and externalizing at age 18; sleep- movement persistence was associated with externalizing and ADHD at age 9, and ADHD at age 18. The age 18 persistence effects for insomnia and anxiety and for sleep movement and ADHD were significant when controlling for earlier mental health. CONCLUSIONS: Childhood insomnia and sleep movement are common and associated with mental health symptoms. Their persistence from middle to late childhood predicts associations with specific types of mental health symptoms at age 18.

18 Article Insomnia nature, diagnosis, and treatment. 2011

Morin, Charles M / Benca, Ruth M. ·Université Laval, Quebec, Canada. cmorin@psy.ulaval.ca ·Handb Clin Neurol · Pubmed #21056225.

ABSTRACT: -- No abstract --

19 Article Prospective associations of insomnia markers and symptoms with depression. 2010

Szklo-Coxe, Mariana / Young, Terry / Peppard, Paul E / Finn, Laurel A / Benca, Ruth M. ·College of Health Sciences, Old Dominion University, Norfolk, VA 23529, USA. mszklo@odu.edu ·Am J Epidemiol · Pubmed #20167581.

ABSTRACT: Whether insomnia, a known correlate of depression, predicts depression longitudinally warrants elucidation. The authors examined 555 Wisconsin Sleep Cohort Study participants aged 33-71 years without baseline depression or antidepressant use who completed baseline and follow-up overnight polysomnography and had complete questionnaire-based data on insomnia and depression for 1998-2006. Using Poisson regression, they estimated relative risks for depression (Zung scale score > or =50) at 4-year (average) follow-up according to baseline insomnia symptoms and polysomnographic markers. Twenty-six participants (4.7%) developed depression by follow-up. Having 3-4 insomnia symptoms versus none predicted depression risk (age-, sex-, and comorbidity-adjusted relative risk (RR) = 3.2, 95% confidence interval: 1.1, 9.6). After multiple adjustments, frequent difficulty falling asleep (RR = 5.3, 95% confidence interval: 1.1, 27.9) and polysomnographically assessed (upper or lower quartiles) sleep latency, continuity, and duration (RRs = 2.2-4.7; P's < or = 0.05) predicted depression. Graded trends (P-trend < or = 0.05) were observed with increasing number of symptoms, difficulty falling asleep, and difficulty returning to sleep. Given the small number of events using Zung > or =50 (depression cutpoint), a limitation that may bias multivariable estimates, continuous depression scores were analyzed; mean values were largely consistent with dichotomous findings. Insomnia symptoms or markers increased depression risk 2.2- to 5.3-fold. These results support prior findings based on self-reported insomnia and may extend similar conclusions to objective markers. Heightened recognition and treatment of insomnia may prevent subsequent depression.