Bright Light as a Personalized Precision Treatment of Mood Disorders

Background: The use of light for its antidepressant action dates back to the beginnings of civilization. Three decades ago, the use of bright-light therapy (BLT) for treating Seasonal Affective Disorder (SAD) was officially proposed. Since then, a growing scientific literature reports its antidepressant efficacy in both unipolar and bipolar disorders (BD), with or without seasonal patterns. This review aims to examine the management of BLT as a personalized and precision treatment in SAD, unipolar, and BD.Methods: We conducted a narrative review using Medline and Google Scholar databases up to June 2018.Results: BLT has physiological effects by resynchronizing the biological clock (circadian system), enhancing alertness, increasing sleep pressure (homeostatic system), and acting on serotonin, and other monoaminergic pathways. Effects of BLT on mood depend on several factors such as light intensity, wavelength spectrum, illumination duration, time of the day, and individual circadian rhythms. A growing body of evidence has been generated over the last decade about BLT evolving as an effective depression treatment not only to be used in SAD, but also in non-seasonal depression, with efficiency comparable to fluoxetine, and possibly more robust in patients with BD. The antidepressant action of BLT is fast (within 1-week) and safe, with the need in BD to protect against manic switch with mood stabilizers. Side effects might be nausea, diarrhea, headache, and eye irritation, and are generally mild and rare. This good safety profile may be of particular interest, especially in women during the perinatal period or for the elderly. The management of BLT needs to be clarified across mood disorders and future studies are expected to compare different dose-titration protocols, to validate its use as a maintenance treatment, and also to identify predictive biomarkers of response and tolerability. We propose clinical guidelines for BLT use in SAD, non-seasonal depression, and BD.Conclusions : BLT is an efficient antidepressant strategy in mono- or adjunct-therapy, that should be personalized according the unipolar or bipolar subtype, the presence or absence of seasonal patterns, and also regarding its efficacy and tolerability

Relationship between childhood physical abuse and clinical severity of treatment-resistant depression in a geriatric population

Introduction: We assessed the correlation between childhood maltreatment (CM) and severity of depression in an elderly unipolar Treatment-Resistant Depression (TRD) sample. Methods: Patients were enrolled from a longitudinal cohort (FACE-DR) of the French Network of Expert TRD Centres. Results: Our sample included 96 patients (33% of the overall cohort) aged 60 years or above, with a mean age of 67.2 (SD = 5.7). The majority of the patients were female (62.5%). The Montgomery and Asberg Depression Rating Scale (MADRS) and Quick Inventory Depression Scale-Self Report (QIDS-SR) mean scores were high, 28.2 (SD = 7.49) [MADRS score range: 0–60; moderate severity≥20, high severity≥35] and 16.5 (SD = 4.94) [IDS-SR score range: 0–27; moderate severity≥11, high severity≥16], respectively. Mean self-esteem scores were 22.47 (SD = 6.26) [range 0–30]. In an age- and sex-adjusted model, we found a positive correlation between childhood trauma (CTQ scores) and depressive symptom severity [MADRS (β = 0.274; p = 0.07) and QIDS-SR (β = 0.302; p = 0.005) scores]. We detected a statistically significant correlation between physical abuse and depressive symptom severity [MADRS (β = 0.304; p = 0.03) and QIDS-SR (β = 0.362; p = 0.005) scores]. We did not observe any significant correlation between other types of trauma and depressive symptom severity. We showed that self-esteem (Rosenberg scale) mediated the effect of physical abuse (PA) on the intensity of depressive symptoms [MADRS: b = 0.318, 95% BCa C.I. [0.07, 0.62]; QIDS-SR: b = 0.177, 95% BCa C.I. [0.04, 0.37]]. Preacher & Kelly’s Kappa Squared values of 19.1% (k2 = 0.191) and 16% (k2 = 0.16), respectively for the two scales, indicate a moderate effect. Conclusion: To our knowledge, this is the first study conducted in a geriatric TRD population documenting an association between childhood trauma (mainly relating to PA) and the intensity of depressive symptoms

International Expert Opinions and Recommendations on the Use of Melatonin in the Treatment of Insomnia and Circadian Sleep Disturbances in Adult Neuropsychiatric Disorders

Introduction: Insomnia and circadian rhythm disorders, such as the delayed sleep phase syndrome, are frequent in psychiatric disorders and their evaluation and management in early stages should be a priority. The aim of this paper was to express recommendations on the use of exogenous melatonin, which exhibits both chronobiotic and sleep-promoting actions, for the treatment of these sleep disturbances in psychiatric disorders.Methods: To this aim, we conducted a systematic review according to PRISMA on the use of melatonin for the treatment of insomnia and circadian sleep disorders in neuropsychiatry. We expressed recommendations for the use of melatonin in psychiatric clinical practice for each disorder using the RAND/UCLA appropriateness method.Results: We selected 41 studies, which included mood disorders, schizophrenia, substance use disorders, attention deficit hyperactivity disorders, autism spectrum disorders, neurocognitive disorders, and delirium; no studies were found for both anxiety and eating disorders.Conclusion: The administration of prolonged release melatonin at 2–10 mg, 1–2 h before bedtime, might be used in the treatment of insomnia symptoms or comorbid insomnia in mood disorders, schizophrenia, in adults with autism spectrum disorders, neurocognitive disorders and during sedative-hypnotics discontinuation. Immediate release melatonin at <1 mg might be useful in the treatment of circadian sleep disturbances of neuropsychiatric disorders

La saisonnalité et l’horloge biologique dans les troubles bipolaires

Bipolar disorders (BD) are severe psychiatric disorders of multifactorial origin with very heterogeneous clinical presentations. BD with seasonal characteristics (CS +) are of major interest because this pattern is frequent, recurrent and associated with more severe BD clinical characteristics and outcomes. My thesis objective is to identify biomarkers associated with CS in BD. My hypothesis is that there is a global vulnerability of the biological clock in these patients with BD, with both circadian and infradian abnormalities. I assessed circadian rhythms and sleep patterns of patients with BD CS + in remission, compared with remitted patients CS- and healthy control subjects, using self - questionnaires and actigraphy. The univariate analysis showed that CS + patients, compared to CS- and control subjects, had a significantly longer sleep latency. CS + patients, compared to CS-, had daytime sleepiness and were significantly more frequently treated with lithium and Atypical Antipsychotics (APA). Univariate analysis showed no differences in phase markers (CSM, M10 onset, L5 onset), stability markers (CTI FR, inter-day stability) and circadian rhythms amplitude (CTI LV, Amplitude activity). The logistic binary regression retained the effect of lithium and APA on CS. We did not observe abnormalities of the circadian rhythms and sleep associated with CS in patients with BD. Nevertheless this work paves the way for future research as assessing the effect of the lithium and the APA on infradian rhythms.Les troubles bipolaires (TB) sont des troubles psychiatriques sévères, d’origine multifactorielle et aux présentations cliniques très hétérogènes. Le TB avec caractéristiques saisonnières (CS+) est fréquent, récurrent et associé à des caractéristiques plus sévères des TB. L'objectif de ma thèse a été de rechercher des biomarqueurs associés à la saisonnalité dans les TB. Mon intérêt s’est porté sur les biomarqueurs circadiens dans l’hypothèse d’une vulnérabilité globale de l’horloge biologique chez ces patients avec TB. J’ai comparé les caractéristiques des rythmes circadiens et du sommeil de patients avec TB en rémission CS+, comparés à des patients en rémission CS- et à des sujets contrôles sains, à l’aide d’auto-questionnaires et de l’actigraphie. L’étape univariée a montré que les patients CS+, comparés aux CS- et aux sujets contrôles, ont une latence d’endormissement significativement plus importante. Par ailleurs, les patients CS+, comparés aux CS-, ont une somnolence diurne excessive plus importante, et étaient significativement plus souvent traités par lithium et Antipsychotiques Atypiques (APA). L’analyse univariée n’a pas montré de différence sur les marqueurs de phase (CSM, début M10, début L5), les marqueurs de stabilité (CTI FR, stabilité inter-jour) et d’amplitude des rythmes circadiens (CTI LV, amplitude activité). L’analyse de régression logistique binaire a retenu l’effet du lithium et des APA sur la CS. Ce travail n’observe pas d’anomalies des rythmes circadiens et du sommeil associés aux troubles des rythmes saisonniers chez les patients avec TB et ouvre des pistes de réflexion sur l’effet du lithium et des APA sur les troubles des rythmes infradiens

Les I.V.G. chez les femmes de plus de 35 ans

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocSudocFranceF

Topical sirolimus 1% for benign lymphangiomatous papules after radiotherapy for endometrial and breast cancers: a report of three cases

International audienc

Mifepristone and misoprostol for cervical ripening in surgical abortion ă between 12 and 14 weeks of gestation: a randomized controlled trial

International audienceObjective: Misoprostol and mifepristone are the two substances ă recommended for cervical preparation during first -trimester surgical ă abortions to decrease intraoperative bleeding and complications. The ă objective of the study was to evaluate whether the combination of ă mifepristone and misoprostol for cervical preparation in an elective ă surgical abortion between 12 and 14 weeks of gestation can reduce blood ă loss in comparison to misoprostol or mifepristone alone. ă Study design: A randomized controlled trial was performed in Marseille, ă France between May 2013 and May 2014. Women requesting a surgical ă abortion under general anesthesia between 12 and 14 weeks of gestation ă were 198, randomized into three groups: one received 400 mu g oral ă misoprostol 3 h before surgery, one 200 mg oral mifepristone 36 h before ă surgery, and the other, both treatments. The main outcome was the ă quantity of intraoperative bleeding. The secondary outcomes were ă duration of intervention, ease of dilatation, and complications. ă Results: The quantity of intraoperative bleeding differed significantly ă between the groups (p = 0.001): 222 +/- 64 mL in the combination group, ă 329 +/- 129 mL in the misoprostol group, and 276 +/- 119 mL in the ă mifepristone group. The combination was associated with a shorter ă operative duration (p = 0.001): 5 +/- 2 min in the combination group, 7 ă +/- 5 min in the misoprostol group, and 7 +/- 3 min in the mifepristone ă group. A hemorrhage was observed for 5 of 55 women (9%) in the ă combination group, 13 of 51(25%) in the misoprostol group, and 9 of 56 ă (16%) in the mifepristone group (p = 0.08). No cervical laceration or ă uterine perforation was reported. ă Conclusions: The combination of mifepristone and misoprostol in cervical ă preparation for elective surgical abortions between 12 and 14 weeks of ă gestation significantly reduced blood loss in comparison to misoprostol ă or mifepristone alone. (C) 2016 Elsevier Ireland Ltd. All rights ă reserved

Examen pelvien en gynécologie et obstétrique ::recommandations pour la pratique clinique

Objectif : Élaborer des recommandations pour l’examen clinique pelvien en gynécologie et obstétrique. Matériel et méthodes : Un groupe de travail multidisciplinaire de 45 experts a été constitué, comprenant des représentants d’associations de patients et d’usagers du système de santé. L’ensemble du processus de ces recommandations a été mené indépendamment de tout financement. Il a été conseillé aux auteurs de suivre les règles du système GRADE® (Grading of Recommendations Assessment, Development and Evaluation) pour évaluer la qualité des preuves. Les limites potentielles de faire des recommandations fortes en présence de preuves de faible qualité ont été soulignées. Le comité a étudié 40 questions dans 4 domaines pour les femmes symptomatiques ou asymptomatiques (urgence, consultation gynécologique, maladies gynécologiques, obstétrique et grossesse). Chaque question a été formulée dans un format PICO (Patients, Intervention, Comparaison, Résultat) et les éléments de preuve ont été détaillés. La revue de la littérature et les recommandations ont été réalisées selon la méthodologie GRADE®. Résultats : Le travail de synthèse des experts et l’application de la méthode GRADE ont abouti à 27 recommandations. Parmi les recommandations formalisées, 17 présentaient un accord fort, 7 un accord faible et 3 un accord professionnel. Treize questions ont donné lieu à une absence de recommandation en raison du manque de preuves (pas de réponse dans la littérature). Conclusions : Les 27 recommandations ont permis de préciser quand un examen clinique est requis pour différentes situations cliniques gynécologiques et obstétricales. Ces recommandations intéressent tout professionnel impliqué dans la santé des femmes. La nécessité de réaliser un examen clinique chez certaines patientes dans certaines situations a été fondée sur des preuves scientifiques. Des recherches supplémentaires sont nécessaires pour étudier les avantages dans d’autres situations.Objective : To provide guidelines for the pelvic clinical exam in gynecology and obstetrics. Material and methods : A multidisciplinary experts consensus committee of 45 experts was formed, including representatives of patients’ associations and users of the health system. The entire guidelines process was conducted independently of any funding. The authors were advised to follow the rules of the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Methods : The committee studied 40 questions within 4 fields for symptomatic or asymptomatic women (emergency conditions, gynecological consultation, gynecological diseases, obstetrics, and pregnancy). Each question was formulated in a PICO (Patients, Intervention, Comparison, Outcome) format and the evidence profiles were produced. The literature review and recommendations were made according to the GRADE® methodology. Results : The experts’ synthesis work and the application of the GRADE method resulted in 27 recommendations. Among the formalized recommendations, 17 present a strong agreement, 7 a weak agreement and 3 an expert consensus agreement. Thirteen questions resulted in an absence of recommendation due to lack of evidence in the literature. Conclusions : The need to perform clinical examination in gynecological and obstetrics patients was specified in 27 pre-defined situations based on scientific evidence. More research is required to investigate the benefit in other cases

The Effects of Transcranial Electrical Stimulation of the Brain on Sleep: A Systematic Review

International audienceTranscranial Electrical Stimulation (tES) is a promising non-invasive brain modulation tool. Over the past years, there have been several attempts to modulate sleep with tES-based approaches in both the healthy and pathological brains. However, data about the impact on measurable aspects of sleep remain scattered between studies, which prevent us from drawing firm conclusions. We conducted a systematic review of studies that explored the impact of tES on neurophysiological sleep oscillations, sleep patterns measured objectively with polysomnography, and subjective psychometric assessments of sleep in both healthy and clinical samples. We searched four main electronic databases to identify studies until February 2020. Forty studies were selected including 511 healthy participants and 452 patients. tES can modify endogenous brain oscillations during sleep. Results concerning changes in sleep patterns are conflicting, whereas subjective assessments show clear improvements after tES. Possible stimulation-induced mechanisms within specific cortico-subcortical sleep structures and networks are discussed. Although these findings cannot be directly transferred to the clinical practice and sleep-enhancing devices development for healthy populations, they might help to pave the way for future researches in these areas. PROSPERO registration number 178910