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1.
Expert Opin Pharmacother ; : 1-9, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33711243

RESUMO

INTRODUCTION: Insomnia is a complex sleep disorder that compromises quality of life and affects approximately 10% of the general population. Insomnia, defined as trouble initiating or maintaining sleep associated with impaired daytime function or distress, is treated using a comprehensive approach comprised of cognitive behavioral therapy and pharmacotherapy. Lemborexant, a dual orexin receptor antagonist, is a new pharmacotherapeutic option recently approved for the treatment of insomnia. AREAS COVERED: Here, the authors describe lemborexant, assess its efficacy and safety profile in clinical trials, and evaluate its role in the current insomnia treatment landscape. EXPERT OPINION: Lemborexant may offer an improved treatment option compared with other pharmacotherapies for insomnia because it is effective both over the long term and over a wide range of outcome measures. Importantly, lemborexant improves latency to sleep onset and sleep maintenance and is able to help people who experience early morning awakenings. Safety data reveal that lemborexant has minimal residual effects on morning alertness or next day function, and that patients are able to respond to an external auditory stimulus in the middle of the night. In conclusion, lemborexant represents a new, effective, and well-tolerated medication for patients with insomnia.

2.
Nat Med ; 27(2): 229-231, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33462446

RESUMO

Deep brain stimulation is a promising treatment for severe depression, but lack of efficacy in randomized trials raises questions regarding anatomical targeting. We implanted multi-site intracranial electrodes in a severely depressed patient and systematically assessed the acute response to focal electrical neuromodulation. We found an elaborate repertoire of distinctive emotional responses that were rapid in onset, reproducible, and context and state dependent. Results provide proof of concept for personalized, circuit-specific medicine in psychiatry.


Assuntos
Encéfalo/ultraestrutura , Estimulação Encefálica Profunda/efeitos adversos , Transtorno Depressivo Maior/terapia , Estimulação Elétrica/efeitos adversos , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Mapeamento Encefálico , Estimulação Encefálica Profunda/métodos , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/fisiopatologia , Estimulação Elétrica/métodos , Eletrodos , Feminino , Humanos
3.
Clin Neurophysiol ; 132(2): 545-553, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33450577

RESUMO

OBJECTIVE: To determine the best of commonly used methods for computing the rate of decline in non-rapid eye movement (NREM) sleep EEG delta power overnight (Delta Decline) in terms of vulnerability to missing data and to evaluate whether this rate is slower in insomnia patients than healthy controls (HC). METHODS: Fifty-one insomnia patients and 53 HC underwent 6 nights of polysomnography. Four methods for estimating Delta Decline were compared (exponential and linear best-fit functions using NREM (1) episode mean, (2) peak, and (3) total delta power and (4) delta power for all available NREM epochs). The best method was applied to compare groups on linear and exponential rates of Delta Decline. RESULTS: Best-fit models using all available NREM epochs were significantly less vulnerable to deviation due to missing data than other methods. Insomnia patients displayed significantly slower linear and exponential Delta Decline than HC. CONCLUSIONS: Computing Delta Decline using all available NREM epochs was the best of the methods studied for minimizing the effects of missing data. Insomnia patients display slower Delta Decline, which is not explained by differences in total sleep time or wake after sleep onset. SIGNIFICANCE: This study supports using all available NREM epochs in Delta Decline computation and suggests a slower rate in insomnia.

4.
J Affect Disord ; 278: 288-295, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-32979560

RESUMO

BACKGROUND: Circadian rhythm disturbances have been reported in patients with major depressive disorder (MDD). Among these is an increased phase angle between peak cortisol concentration and dim-light melatonin onset (DLMO). The aim of this study was to evaluate changes in chronobiologic parameters of sleep in patients with MDD receiving adjunctive brexpiprazole. METHODS: This was an interventional, multicenter, open-label, flexible-dose, exploratory study in patients with MDD and inadequate response to antidepressant treatment who were experiencing sleep disturbances. Patients received adjunctive brexpiprazole 2-3 mg/day for 8 weeks. Outcome measures included cortisol and melatonin levels, used to calculate phase angle, and the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN). RESULTS: The mean (standard error) phase angle between peak cortisol and DLMO increased by 108 (61) minutes from baseline to Week 8 (n = 9). BRIAN Total score changed (improved) by -14.6 (4.6) points from baseline to Week 8 (n = 9). Change in phase angle and BRIAN Total score showed a moderate-to-high correlation (Pearson coefficient: 0.68; 95% confidence limits: 0.04, 0.93; p = 0.040). LIMITATIONS: This study is limited by its small sample size, and its single-arm, open-label design. CONCLUSIONS: The findings provide a preliminary indication that the phase angle between peak cortisol and DLMO is of interest as a potential biomarker for depression and therapeutic response. Adjunctive brexpiprazole may represent a strategy for correcting circadian dysfunction in patients with MDD and inadequate response to antidepressant treatment. ClinicalTrials.gov identifier: NCT01942733.


Assuntos
Transtorno Depressivo Maior , Melatonina , Ritmo Circadiano , Transtorno Depressivo Maior/tratamento farmacológico , Quimioterapia Combinada , Humanos , Melatonina/uso terapêutico , Quinolonas , Sono , Tiofenos , Resultado do Tratamento
6.
J Patient Rep Outcomes ; 4(1): 100, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33226517

RESUMO

BACKGROUND: The intense itching associated with atopic dermatitis (AD) often causes patients to experience severe sleep disturbance. Here, we describe the results of a two-phase concept elicitation and cognitive interview study to establish the content validity of a sleep disturbance numerical rating scale (SD NRS) and a Consensus Sleep Diary adapted for adults and adolescents with moderate-to-severe AD (CSD-AD©). RESULTS: In phase I, a concept elicitation conducted in 20 adults and 10 adolescents with moderate-to-severe AD revealed that the following sleep-related issues were important and relevant: nighttime awakening (87%), trouble falling asleep (73%), feeling unrested (53%), daytime fatigue or sleepiness (53%), and feeling as if they did not get enough sleep (33%). The frequency and extent of sleep disturbance varied substantially from day to day due to varying degrees of itching and flares, medication use, and changes in the weather. All participants understood the SD NRS question, with most finding it easy or very easy to understand (100% of adults and 90% of adolescents) and most understanding the anchors as intended (95% of adults, and 100% of adolescents). Most participants (94% of adults, and 90% of adolescents) indicated that they would consider a one- or two-point change meaningful on the SD NRS. The CSD-AD© was revised based on participant feedback, and tested during phase II in a convenience sample of six adults and four adolescents from phase I. The changes made to the CSD-AD© were confirmed to be relevant and understandable. All patients were able to provide an answer to each item in the CSD-AD©, and most were able to estimate the duration of nighttime awakenings, daytime naps, and dozing. CONCLUSIONS: The study supported the content validity of the SD NRS and CSD-AD© in adults and adolescents with moderate-to-severe AD. It also emphasized the importance of using these instruments daily when assessing the benefit of a new treatment on sleep quality in this population.

7.
Sleep ; 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33151330

RESUMO

STUDY OBJECTIVES: To examine the cost-effectiveness and potential net monetary benefit of a fully automated digital cognitive behavioral therapy (CBT) intervention for insomnia compared with no insomnia treatment in the United States (US). Similar relative comparisons were made for pharmacotherapy and clinician-delivered CBT (individual and group). METHODS: We simulated a Markov model of 100,000 individuals using parameters calibrated from the literature including direct (treatment) and indirect costs (e.g., insomnia-related healthcare expenditure, lost workplace productivity). Health utility estimates were converted into quality-adjusted life years (QALYs) and one QALY was worth $50,000. Simulated individuals were randomized equally to one of five arms (digital CBT, pharmacotherapy, individual CBT, group CBT or no insomnia treatment). Sensitivity was assessed by bootstrapping the calibrated parameters. Cost estimates were expressed in 2019 US dollars. RESULTS: Digital CBT was cost-beneficial when compared with no insomnia treatment and had a positive net monetary benefit of $681.06 (per individual over 6-months). Bootstrap sensitivity analysis demonstrated that the net monetary benefit was positive in 94.7% of simulations. Relative to other insomnia treatments, digital CBT was the most cost-effective treatment because it generated the smallest incremental cost-effectiveness ratio (-$3,124.73). CONCLUSIONS: Digital CBT was the most cost-effective insomnia treatment followed by group CBT, pharmacotherapy, and individual CBT. It is financially prudent and beneficial from a societal perspective to utilize automated digital CBT to treat insomnia at a population scale.

8.
JMIR Mhealth Uhealth ; 8(10): e20590, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33001035

RESUMO

BACKGROUND: Adolescence is an important life stage for the development of healthy behaviors, which have a long-lasting impact on health across the lifespan. Sleep undergoes significant changes during adolescence and is linked to physical and psychiatric health; however, sleep is rarely assessed in routine health care settings. Wearable sleep electroencephalogram (EEG) devices may represent user-friendly methods for assessing sleep among adolescents, but no studies to date have examined the feasibility and acceptability of sleep EEG wearables in this age group. OBJECTIVE: The goal of the research was to investigate the feasibility and acceptability of sleep EEG wearable devices among adolescents aged 11 to 17 years. METHODS: A total of 104 adolescents aged 11 to 17 years participated in 7 days of at-home sleep recording using a self-administered wearable sleep EEG device (Zmachine Insight+, General Sleep Corporation) as well as a wristworn actigraph. Feasibility was assessed as the number of full nights of successful recording completed by adolescents, and acceptability was measured by the wearable acceptability survey for sleep. Feasibility and acceptability were assessed separately for the sleep EEG device and wristworn actigraph. RESULTS: A total of 94.2% (98/104) of adolescents successfully recorded at least 1 night of data using the sleep EEG device (mean number of nights 5.42; SD 1.71; median 6, mode 7). A total of 81.6% (84/103) rated the comfort of the device as falling in the comfortable to mildly uncomfortable range while awake. A total of 40.8% (42/103) reported typical sleep while using the device, while 39.8% (41/103) indicated minimal to mild device-related sleep disturbances. A minority (32/104, 30.8%) indicated changes in their sleep position due to device use, and very few (11/103, 10.7%) expressed dissatisfaction with their experience with the device. A similar pattern was observed for the wristworn actigraph device. CONCLUSIONS: Wearable sleep EEG appears to represent a feasible, acceptable method for sleep assessment among adolescents and may have utility for assessing and treating sleep disturbances at a population level. Future studies with adolescents should evaluate strategies for further improving usability of such devices, assess relationships between sleep EEG-derived metrics and health outcomes, and investigate methods for incorporating data from these devices into emerging digital interventions and applications. TRIAL REGISTRATION: ClinicalTrials.gov NCT03843762; https://clinicaltrials.gov/ct2/show/NCT03843762.

9.
Curr Biol ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33065013

RESUMO

Sufficient and efficient sleep is crucial for our health. Natural short sleepers can sleep significantly shorter than the average population without a desire for more sleep and without any obvious negative health consequences. In searching for genetic variants underlying the short sleep trait, we found two different mutations in the same gene (metabotropic glutamate receptor 1) from two independent natural short sleep families. In vitro, both of the mutations exhibited loss of function in receptor-mediated signaling. In vivo, the mice carrying the individual mutations both demonstrated short sleep behavior. In brain slices, both of the mutations changed the electrical properties and increased excitatory synaptic transmission. These results highlight the important role of metabotropic glutamate receptor 1 in modulating sleep duration.

10.
Hum Psychopharmacol ; : e2757, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32918323

RESUMO

OBJECTIVES: Information is lacking regarding how commonly unblinding of treatment assignment occurs in hypnotic randomized clinic trials (RCTs). We now report the "best guesses" of clinical trial participants, versus study coordinators, versus study physicians in the study Reducing Suicidal Ideation Through Insomnia Treatment (REST-IT). METHODS: REST-IT, a, 8-week double-blind RCT, compared zolpidem extended-release (ER) versus placebo at bedtime in 103 adults with major depressive disorder with insomnia and suicidal ideation, and who received open label selective serotonin reuptake inhibitors. At the conclusion of study participation, 89 of the participants in this study, the study coordinators, and the study physicians each independently recorded their "best guess" of the treatment assigned. RESULTS: Patients guessed correctly 58.4% of the time, coordinators 53.9% of the time, and physicians 49.4% of the time, and none were different from chance alone. Agreement between patient/coordinator, patient/doctor, and coordinator/doctor dyads were 75%-78% with no significant differences in agreement between the dyads. CONCLUSIONS: "Best guesses" of all parties were not different from chance, suggesting that the blind was maintained and that assessment bias was minimized in this RCT of zolpidem ER versus placebo. Our results may not apply to other hypnotics or other RCT designs.

11.
JAMA Psychiatry ; 2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32639561

RESUMO

Importance: Despite evidence of efficacious psychological and pharmacologic therapies for insomnia, there is little information about what first-line treatment should be and how best to proceed when initial treatment fails. Objective: To evaluate the comparative efficacy of 4 treatment sequences involving psychological and medication therapies for insomnia and examine the moderating effect of psychiatric disorders on insomnia outcomes. Design, Setting, and Participants: In a sequential multiple-assignment randomized trial, patients were assigned to first-stage therapy involving either behavioral therapy (BT; n = 104) or zolpidem (zolpidem; n = 107), and patients who did not remit received a second treatment involving either medication (zolpidem or trazodone) or psychological therapy (BT or cognitive therapy [CT]). The study took place at Institut Universitaire en Santé Mentale de Québec, Université Laval, Québec City, Québec, Canada, and at National Jewish Health, Denver, Colorado, and enrollment of patients took place from August 2012 through July 2017. Main Outcomes and Measures: The primary end points were the treatment response and remission rates, defined by the Insomnia Severity Index total score. Results: Patients included 211 adults (132 women; mean [SD] age, 45.6 [14.9] years) with a chronic insomnia disorder, including 74 patients with a comorbid anxiety or mood disorder. First-stage therapy with BT or zolpidem produced equivalent weighted percentages of responders (BT, 45.5%; zolpidem, 49.7%; OR, 1.18; 95% CI, 0.60-2.33) and remitters (BT, 38.03%; zolpidem, 30.3%; OR, 1.41; 95% CI, 0.75-2.65). Second-stage therapy produced significant increases in responders for the 2 conditions, starting with BT (BT to zolpidem, 40.6% to 62.7%; OR, 2.46; 95% CI, 1.14-5.30; BT to CT, 50.1% to 68.2%; OR, 2.09; 95% CI, 1.01-4.35) but no significant change following zolpidem treatment. Significant increase in percentage of remitters was observed in 2 of 4 therapy sequences (BT to zolpidem, 38.1% to 55.9%; OR, 2.06; 95% CI, 1.04-4.11; zolpidem to trazodone, 31.4% to 49.4%; OR, 2.13; 95% CI, 0.91-5.00). Although response/remission rates were lower among patients with psychiatric comorbidity, treatment sequences that involved BT followed by CT or zolpidem followed by trazodone yielded better outcomes for patients with comorbid insomnia. Response and remission rates were well sustained through the 12-month follow-up. Conclusions and Relevance: Behavioral therapy and zolpidem medication produced equivalent response and remission rates. Adding a second treatment produced an added value for those whose insomnia failed to remit with initial therapies. Trial Registration: ClinicalTrials.gov Identifier: NCT01651442.

12.
Neuropsychopharmacology ; 45(10): 1656-1663, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32544925

RESUMO

Anhedonia remains a major clinical issue for which there is few effective interventions. Untreated or poorly controlled anhedonia has been linked to worse disease course and increased suicidal behavior across disorders. Taking a proof-of-mechanism approach under the auspices of the National Institute of Mental Health FAST-FAIL initiative, we were the first to show that, in a transdiagnostic sample screened for elevated self-reported anhedonia, 8 weeks of treatment with a kappa-opioid receptor (KOR) antagonist resulted in significantly higher reward-related activation in one of the core hubs of the brain reward system (the ventral striatum), better reward learning in the Probabilistic Reward Task (PRT), and lower anhedonic symptoms, relative to 8 weeks of placebo. Here, we performed secondary analyses of the PRT data to investigate the putative effects of KOR antagonism on anhedonic behavior with more precision by using trial-level model-based Bayesian computational modeling and probability analyses. We found that, relative to placebo, KOR antagonism resulted in significantly higher learning rate (i.e., ability to learn from reward feedback) and a more sustained preference toward the more frequently rewarded stimulus, but unaltered reward sensitivity (i.e., the hedonic response to reward feedback). Collectively, these findings provide novel evidence that in a transdiagnostic sample characterized by elevated anhedonia, KOR antagonism improved the ability to modulate behavior as a function of prior rewards. Together with confirmation of target engagement in the primary report (Krystal et al., Nat Med, 2020), the current findings suggest that further transdiagnostic investigation of KOR antagonism for anhedonia is warranted.

13.
Sleep Breath ; 24(4): 1633-1643, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32458375

RESUMO

PURPOSE: Pulse oximetry is the current standard for detecting drops in arterial blood oxygen saturation (SpO2) associated with obstructive sleep apnea and hypopnea events in polysomnographic (PSG) testing. However, cellular energy monitoring (CE monitoring), a measure related to cellular hypoxia in the skin, is likely to be more responsive to inadequate breathing during sleep because during hypoxic challenge, such as occurs during apneic events, regulatory mechanisms restrict blood flow to the skin to preferentially maintain SpO2 for more vital organs. We carried out initial proof of concept testing to determine if CE monitoring has promise for being more responsive to hypoxic challenge occurring during sleep-disordered breathing (SDB) than pulse oximetry. METHODS: We assessed both CE monitoring and pulse oximetry in a series of conditions which affect oxygen supply: (1) breathing nitrogen or 100% oxygen, (2) physical exertion, and (3) studying a night of sleep in an individual known to be a loud snorer. We also present the results of a preliminary study comparing CE monitoring to pulse oximetry in eight individuals undergoing standard clinical overnight polysomnography for suspected SDB. RESULTS: CE monitoring is responsive to changes in cellular oxygen supply to the skin and detects hypoxia during SDB events that is not detected by pulse oximetry. CONCLUSION: CE monitoring is a promising tool for identifying pathology at the mild end of the SDB spectrum.

14.
JAMA Psychiatry ; 77(7): 768, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32320022
15.
J Clin Sleep Med ; 16(8): 1311-1319, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32329435

RESUMO

STUDY OBJECTIVES: Sleep 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. METHODS: We 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. RESULTS: Over 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. CONCLUSIONS: Self-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 REGISTRATION: Registry: 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.

16.
Nat Med ; 26(5): 760-768, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32231295

RESUMO

The National Institute of Mental Health (NIMH) 'fast-fail' approach seeks to improve too-often-misleading early-phase drug development methods by incorporating biomarker-based proof-of-mechanism (POM) testing in phase 2a. This first comprehensive application of the fast-fail approach evaluated the potential of κ-opioid receptor (KOR) antagonism for treating anhedonia with a POM study determining whether robust target engagement favorably impacts the brain circuitry hypothesized to mediate clinical effects. Here we report the results from a multicenter, 8-week, double-blind, placebo-controlled, randomized trial in patients with anhedonia and a mood or anxiety disorder (selective KOR antagonist (JNJ-67953964, 10 mg; n = 45) and placebo (n = 44)). JNJ-67953964 significantly increased functional magnetic resonance imaging (fMRI) ventral striatum activation during reward anticipation (primary outcome) as compared to placebo (baseline-adjusted mean: JNJ-67953964, 0.72 (s.d. = 0.67); placebo, 0.33 (s.d. = 0.68); F(1,86) = 5.58, P < 0.01; effect size = 0.58 (95% confidence interval, 0.13-0.99)). JNJ-67953964, generally well tolerated, was not associated with any serious adverse events. This study supports proceeding with assessment of the clinical impact of target engagement and serves as a model for implementing the 'fast-fail' approach.


Assuntos
Anedonia/efeitos dos fármacos , Benzamidas/uso terapêutico , Transtornos do Humor/tratamento farmacológico , Antagonistas de Entorpecentes/uso terapêutico , Pirrolidinas/uso terapêutico , Receptores Opioides kappa/antagonistas & inibidores , Adulto , Transtornos de Ansiedade/complicações , Transtornos de Ansiedade/tratamento farmacológico , Transtornos de Ansiedade/psicologia , Fármacos do Sistema Nervoso Central/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/complicações , Transtornos do Humor/psicologia , Estudo de Prova de Conceito , Fatores de Tempo , Resultado do Tratamento
17.
JAMA Psychiatry ; 77(5): 484-492, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31968068

RESUMO

Importance: Despite the prevalence and adverse consequences of prenatal insomnia, a paucity of research is available regarding interventions to improve insomnia symptoms during pregnancy. Objective: To test the efficacy of digital cognitive behavioral therapy for insomnia (CBT-I) compared with standard treatment among pregnant women with insomnia symptoms. Design, Setting, and Participants: This randomized clinical trial enrolled pregnant women from November 23, 2016, to May 22, 2018. Of the 2258 women assessed for eligibility using an online self-report questionnaire, 208 were randomized to receive digital CBT-I (n = 105) or standard treatment (n = 103) for insomnia. Participants were pregnant up to 28 weeks' gestation, and they either had elevated insomnia symptom severity or met the criteria for insomnia caseness as determined by self-report questionnaires. Participants completed outcome measures at 10 weeks (postintervention) and 18 weeks (follow-up) after randomization. All study visits were completed remotely, and the intervention was delivered digitally. Data were analyzed between December 12, 2018, and July 2, 2019. Interventions: Digital CBT-I consisted of 6 weekly sessions of approximately 20 minutes each. Standard treatment reflected standard care. Women receiving standard treatment had no limits placed on the receipt of nonstudy treatments, including medication and psychotherapy. Main Outcomes and Measures: All outcomes were assessed remotely using self-report questionnaires administered via online survey. The primary outcome was the change in insomnia symptom severity (measured by the Insomnia Severity Index) from baseline to postintervention. Secondary outcomes were sleep efficiency and nightly sleep duration (defined by sleep diary), global sleep quality (measured by the Pittsburgh Sleep Quality Index), depressive symptom severity (measured by the Edinburgh Postnatal Depression Scale), and anxiety symptom severity (measured by the Generalized Anxiety Disorder Scale-7). For each outcome, we also examined the change from baseline to follow-up. Results: The 208 participants had a mean (SD) age of 33.6 (3.7) years and a mean (SD) gestational age of 17.6 (6.3) weeks at baseline. Most of the participants were white (138 [66.3%]), married or cohabiting (196 [94.2%]), had a college degree (180 [86.5%]), and earned $100 000 or more per year (141 [67.8%]). Women randomized to receive digital CBT-I experienced statistically significantly greater improvements in insomnia symptom severity from baseline to postintervention compared with women randomized to receive standard treatment (time-by-group interaction, difference = -0.36; 95% CI, -0.48 to -0.23; χ2 = 29.8; P < .001; d = -1.03). Improvements from baseline to postintervention for all secondary outcomes, with the exception of sleep duration, were statistically significant. A similar pattern of results was evident for the change from baseline to follow-up. Conclusions and Relevance: In this trial, digital CBT was an effective, scalable, safe, and acceptable intervention for improving insomnia symptoms during pregnancy. Trial Registration: ClinicalTrials.gov identifier: NCT02805998.

18.
J Neuropsychiatry Clin Neurosci ; 32(2): 185-190, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31394989

RESUMO

OBJECTIVES: Adult patients with epilepsy have an increased prevalence of major depressive disorder (MDD). Intracranial EEG (iEEG) captured during extended inpatient monitoring of patients with treatment-resistant epilepsy offers a particularly promising method to study MDD networks in epilepsy. METHODS: The authors used 24 hours of resting-state iEEG to examine the neural activity patterns within corticolimbic structures that reflected the presence of depressive symptoms in 13 adults with medication-refractory epilepsy. Principal component analysis was performed on the z-scored mean relative power in five standard frequency bands averaged across electrodes within a region. RESULTS: Principal component 3 was a statistically significant predictor of the presence of depressive symptoms (R2=0.35, p=0.014). A balanced logistic classifier model using principal component 3 alone correctly classified 78% of patients as belonging to the group with a high burden of depressive symptoms or a control group with minimal depressive symptoms (sensitivity, 75%; specificity, 80%; area under the curve=0.8, leave-one-out cross validation). Classification was dependent on beta power throughout the corticolimbic network and low-frequency cingulate power. CONCLUSIONS: These finding suggest, for the first time, that neural features across circuits involved in epilepsy may distinguish patients who have depressive symptoms from those who do not. Larger studies are required to validate these findings and to assess their diagnostic utility in MDD.


Assuntos
Córtex Cerebral/fisiopatologia , Depressão/fisiopatologia , Epilepsia Resistente a Medicamentos/fisiopatologia , Eletrocorticografia , Sistema Límbico/fisiopatologia , Rede Nervosa/fisiopatologia , Adulto , Biomarcadores , Feminino , Humanos , Masculino , Projetos Piloto , Análise de Componente Principal
19.
Neuropsychopharmacology ; 45(1): 166-175, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31376815

RESUMO

Alterations in sleep are extremely common in patients with neuropsychiatric illness. In addition, sleep disorders such as insomnia, obstructive sleep apnea, rapid eye movement sleep behavior disorder, and circadian rhythm disorders commonly occur at a rate greater than the general population in neuropsychiatric conditions. Historically, sleep problems have been viewed as symptoms of associated neuropsychiatric disorders. However, there is increasing evidence suggesting a complex inter-relationship with possible bidirectional causality. The inter-relatedness of these conditions represents an opportunity for understanding mechanisms and improving clinical treatment. To the extent that sleep problems affect neuropsychiatric conditions, it may be possible to address sleep problems and have a positive impact on the course of neuropsychiatric illnesses. Further, some treatments for sleep disorders have direct effects on neuropsychiatric illnesses that may be unrelated to their effects on sleep disorders. Similarly, neuropsychiatric conditions and their treatments can affect sleep and sleep disorders. This article reviews available evidence on the effects of therapies for sleep disorders on neuropsychiatric conditions and also secondarily considers the impacts of therapies for neuropsychiatric conditions on sleep. Primary goals of this review are to identify gaps in current research, to determine the extent to which the cross-therapeutic effects of these treatments help to elucidate therapeutic or pathological mechanisms, and to assist clinicians in optimizing therapeutic choice in patients with sleep disorders and neuropsychiatric conditions.

20.
Neuropsychopharmacology ; 45(1): 45-54, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31400754

RESUMO

Timing and duration of sleep are controlled by the circadian system, which keeps an ~24-h internal rhythm that entrains to environmental stimuli, and the sleep homeostat, which rises as a function of time awake. There is a normal distribution across the population in how the circadian system aligns with typical day and night resulting in varying circadian preferences called chronotypes. A portion of the variation in the population is controlled by genetics as shown by the single-gene mutations that confer extreme early or late chronotypes. Similarly, there is a normal distribution across the population in sleep duration. Genetic variations have been identified that lead to a short sleep phenotype in which individuals sleep only 4-6.5 h nightly. Negative health consequences have been identified when individuals do not sleep at their ideal circadian timing or are sleep deprived relative to intrinsic sleep need. Whether familial natural short sleepers are at risk of the health consequences associated with a short sleep duration based on population data is not known. More work needs to be done to better assess for an individual's chronotype and degree of sleep deprivation to answer these questions.

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