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Treatment-resistant Depression (TRD) represents a widespread disorder with significant direct and indirect healthcare costs. esketamine, the S-enantiomer of ketamine, has been recently approved for TRD, but real-world studies are needed to prove its efficacy in naturalistic settings.Evaluate the effectiveness and safety of esketamine nasal spray in a clinical sample of patients with TRD from several Italian mental health services.REAL-ESK study is an observational, retrospective and multicentric study comprising a total of 116 TRD patients treated with esketamine nasal spray. Anamnestic data and psychometric assessment (MADRS, HAMD-21, HAM-A) were collected from medical records at baseline (T0), one month (T1) and three month (T2) follow-ups.A significant reduction of depressive symptoms was found at T1 and T2 compared to T0. A dramatic increase in clinical response (64.2 %) and remission rates (40.6 %) was detected at T2 compared to T1. No unexpected safety concerns were observed, side effects rates were comparable to those reported in RCTs. No differences in efficacy have been found among patients with and without psychiatric comorbidities.The open design of the study and the absence of a placebo or active comparator group are limitations. The study lacks an inter-rater reliability evaluation of the assessments among the different centres. Side effects evaluation did not involve any specific scale.Our findings support the safety and tolerability of esketamine in a real-world TRD sample. The later response and the non-inferiority in effectiveness in patients with comorbidities represent novel and interesting findings.

Background: A growing number of neuroimaging studies have revealed spatial abnormalities of resting-state functional brain network activity in bipolar disorder (BD). Conversely, abnormalities of resting state temporal dynamics have been scarcely investigated so far. The aim of this study was to characterize the EEG microstates activity in BD patients with a history of manic predominant polarity. Patients were euthymic and pharmacologically stabilized. Methods: Nineteen BD patients (mean age 34.4 ± 11.0, 7 female) and 19 healthy controls (HC; mean age 38.2 ± 9.9, 7 female) were recruited. The psychometric evaluation included the Hamilton Depression Scale (HAMD), the Young Mania Rating Scale (YMRS), the Dissociative Experience Scale (DES), and the State-Trait Anxiety Inventory (STAI). Two runs of 2 minutes of EEG activity by a 128-channel system were acquired at rest and analyzed through microstate analysis. Results: We found a reduced presence of microstate B in BD patients compared to HC, since BD patients have a tendency to transit from the microstate B to the microstates C and D significantly more than HC. Furthermore, microstate B features were correlated with DES, state STAI and trait STAI scores. Conclusion: The reduced presence of microstate B might be associated with episodic autobiographic memory deficit, exaggerated self-focusing and states of dissociations characteristic of BD. Strong correlations of microstate B metrics and dynamics with symptoms of dissociation and anxiety across the two groups supported this interpretation.

Background The aim of this study was to assess whether different affective temperaments could be related to a specific mood disorder diagnosis and/or to different therapeutic choices in inpatients admitted for an acute relapse of their primary mood disorder. Method Hundred and twenty-nine inpatients were consecutively assessed by means of the Structured and Clinical Interview for axis-I disorders/Patient edition and by the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego auto-questionnaire, Young Mania Rating Scale, Hamilton Scale for Depression and for Anxiety, Brief Psychiatry Rating Scale, Clinical Global impression, Drug Attitude Inventory, Barratt Impulsiveness Scale, Toronto Alexithymia Scale, and Symptoms Checklist-90 items version, along with records of clinical and demographic data. Results The following prevalence rates for axis-I mood diagnoses were detected: bipolar disorder type I (BD-I, 28%), type II (31%), type not otherwise specified (BD-NOS, 33%), major depressive disorder (4%), and schizoaffective disorder (4%). Mean scores on the hyperthymic temperament scale were significantly higher in BD-I and BD-NOS, and in mixed and manic acute states. Hyperthymic temperament was significantly more frequent in BD-I and BD-NOS patients, whereas depressive temperament in BD-II ones. Hyperthymic and irritable temperaments were found more frequently in mixed episodes, while patients with depressive and mixed episodes more frequently exhibited anxious and depressive temperaments. Affective temperaments were associated with specific symptom and psychopathology clusters, with an orthogonal subdivision between hyperthymic temperament and anxious/cyclothymic/depressive/irritable temperaments. Therapeutic choices were often poorly differentiated among temperaments and mood states. Limits Cross-sectional design; sample size. Conclusions Although replication studies are needed, current results suggest that temperament-specific clusters of symptoms severity and psychopathology domains could be described.

Background The co-occurrence of bipolar disorder (BD) and gambling disorder (GD), though of clinical and public health importance, is still scarcely investigated. Comorbid BD–GD subjects experience a more severe course of illness and poorer treatment outcome, due to a range of clinical and psychosocial factors that collectively impede remission and recovery. The aim of our paper is to review the role of pharmacotherapy in the treatment of comorbid BD–GD, in order to support clinical decisions according to the best available evidence. Methods A qualitative systematic review of studies on pharmacological treatment in comorbid BD–GD was performed. A comprehensive literature search of online databases, bibliographies of published articles and gray literature was conducted. Data on efficacy, safety and tolerability were extracted and levels of evidence were assessed. We also provide a brief overview of current epidemiological, neurobiological and clinical findings, with the intention of proposing a dimensional approach to the choice of available drugs. Results The only drug with a high level of evidence is lithium. Considering the inclusion of GD in DSM-5 ‘Substance-related and Addictive Disorders’ category, we discuss the use of other drugs with a high level of evidence currently used in BD subjects with co-occurring substance use disorders. Limitations Only few clinical trials are available and the population is limited; therefore no conclusive evidence can be inferred. Conclusions Further randomized controlled trials are required to evaluate the efficacy of pharmacological treatment strategies in large samples of patients with comorbid BD–GD. Also, attempts should be made to identify other shared clinical and psychopathological domains that are amenable to treatment.

Background: The aim of this study was to evaluate the microstructure of the EEG sleep of depressed subjects by cyclic alternating pattern (CAP) analysis. Methods: 78 patients affected by major depression and 18 control subjects matched for age and sex underwent a full night polysomnographic study. Results: A significant increase in CAP rate (60 versus 35%) was found in the patients group compared to controls while no significant difference was found with the traditional analysis. Conclusion: In depressed subjects CAP analysis is able to show a microstructural sleep impairment, which is not evident at the macrostructural level, providing an objective measure of sleep disturbance in those patients.