Brexpiprazole in patients with schizophrenia with or without substance use disorder: an observational study.

Background: Partial dopamine D2 receptor agonists are used for psychotic symptoms in adults with schizophrenia spectrum disorders. Recently, interest surged for partial dopamine D2 receptor agonists in substance use disorders (SUDs). Since it is believed that SUDs decrease the efficacy of pharmacotherapy of underlying psychiatric disorders, we tested the efficacy of the partial D2 agonist brexpiprazole in patients with schizophrenia who were either comorbid with a SUD (SUD group) or not comorbid (non-SUD) to assess treatment response and the effect of brexpiprazole on substance craving in SUD. Methods: We included patients with DSM-5/DSM-5-TR schizophrenia (using SCID-5-CV) aged 18-66 years with either comorbid SUD or non-SUD to treat with brexpiprazole 4 mg/day for 6 months during February-October 2022. Patients were assessed with the Clinical Global Impressions-Severity (CGI-S) scale, the 24-item Brief Psychiatric Rating Scale (BPRS), and the Positive And Negative Syndrome Scale (PANSS) at baseline, weekly for the first 2 months and monthly for the next four. Furthermore, we assessed substance craving in SUD with a visual analog scale for craving (VAScrav) at the same timepoints. Results: The total sample was 86 (85 analysable) 18- to 64-year-old (mean 39.32 ± 14.09) patients with schizophrenia [51 men (59.3%) and 35 women (40.7%)], of whom 48 SUD (55.8%) (37 men and 11 women) and 38 non-SUD (44.2%) (14 men and 24 women). No serious or persistent adverse events developed over the study period, but one patient dropped out for subjective akathisia. Results indicated the main effects of time with improvements over the course of the study for CGI-S, BPRS, and PANSS in both SUD and non-SUD groups and the entire sample, and for VAScrav in SUD. Brexpiprazole was associated with similar significant improvements in both groups at the 6 month endpoint compared to baseline. Conclusion: Treatment with brexpiprazole for 6 months improved psychotic symptoms in patients with schizophrenia, independently from whether they belonged to the SUD or the non-SUD group; hence, SUD comorbidity did not confer treatment resistance to brexpiprazole. Furthermore, in the SUD group, we observed reduced substance craving.

Differential Response to Three Antidepressants in Patients with Major Depressive Episode Who Suffered Covid-19-Related Trauma.

BACKGROUND: The Covid 19 pandemic might have impacted response to drug treatment in major depressive episode (MDE). We compared responses to three different antidepressant drugs, i.e., vortioxetine, sertraline, and trazodone, in outpatients with MDE during Major Depressive Disorder (MDD), Bipolar Disorder (BD), or schizophrenia and related psychoses (SSOPDs) during two time periods, i.e., before and after suffering Covid-19-related trauma. METHODS: We conducted an observational study on clinically stabilised for at least 6 months outpatients with MDE during the course of MDD (N=58), BD (N=33), or SSOPDs (N=51). Patients, whose baseline assessments of Montgomery-Åsberg Rating Scale (MADRS), Hamilton Anxiety Rating Scale (Ham-A), Brief Psychiatric Rating Scale (BPRS), Visual Analogue Scale for Craving (VAS-crav) and World Health Organization Quality of Life, Brief version (WHOQOL-BREF) were available, were recruited at the time they suffered Covid-19-related traumas. Fifty patients, prior to the pandemic, when they were clinically stable, were treated with 15 mg/die vortioxetine, 44 with 450 mg/die trazodone, and 48 with 150 mg/die sertraline. After experiencing a major Covid-19-related personal trauma, patients showed clinical worsening which required dosage adjustment (20 mg/day vortioxetine; 600 mg/day trazodone, and 200 mg/day sertraline) and, for some of them, hospitalisation. Scores on the MADRS, Ham-A, BPRS, VAS-crav and WHOQOL-BREF were compared drug-wise and genderwise with Student's t test for continuous variables and Χ2 for categorical variables. RESULTS: The sample consisted of 142 outpatients (age, mean 39.63 ± 16.84; 70 men and 72 women); women were older than men (mean age 43.18 ± 17.61 vs. 35.98 ± 15.30; p=0.01). The two genders did not differ on other variables. For all treatments, worsening symptoms were observed at the time of trauma, followed by slow recovery with treatment readjustment. Trauma-related worsening in patients on vortioxetine was less intense than patients on the other two antidepressants and recovery was faster. All drugs were associated with an improvement in QoL. The vortioxetine group showed a lower hospitalisation rate (24%) than sertraline (35.4%) and trazodone (38.6%), but this was not significant (p=0.27). CONCLUSION: All drugs improved symptoms of Covid-19 trauma in patients with MDE, with vortioxetine showing a small advantage. No differences between vortioxetine, sertraline and trazodone were found as concerning the need for hospitalisation.

Burnout and Psychological Vulnerability in First Responders: Monitoring Depersonalization and Phobic Anxiety during the COVID-19 Pandemic.

BACKGROUND: It is common knowledge that first responders are among the helping professionals most at risk of burnout and psychological vulnerability. During the COVID-19 pandemic, their mental health has been subjected to various risk factors. METHODS: Data on socio-demographic characteristics, the Maslach Burnout Inventory (MBI) and psychological vulnerability (SCL-90-R) were obtained from 228 subjects (55.3% female; M age = 45.23, SD = 13.14) grouped on the basis of their actual involvement during the emergency phases (82% First Responders and 18% Second Responders). RESULTS: First responders exceeded the MBI clinical cut-off, while SRs did not (χ² ≥ 0.5); specifically, EE = 89.8%, DP = 85.8%, and PA = 82.1%. The FR group showed a higher mean in the global severity index (GSI = 49.37) than did the SRs (=43.95), and the FR group exceeded the clinical cut-off in the SCL-90-R scales of SOM (51.06), ANX (52.40), and PHOB (53.60), while the SF group did so only for the PHOB scale (50.41). The MBI dimensions correlated significantly (p = 0.05) with all investigated clinical scales of the SCL-90-R. CONCLUSIONS: Emergency situations expose first responders to specific risk factors related to work performance and relational aspects, which contribute to increased psychological vulnerability and burnout.

Treatment-resistant schizophrenia: Addressing white matter integrity, intracortical glutamate levels, clinical and cognitive profiles between early- and adult-onset patients.

BACKGROUND: Treatment-resistance in schizophrenia is 30-40%. Its neurobiology remains unclear; to explore it, we conducted a combined spectrometry/tractography/cognitive battery and psychopathological rating study on patients with treatment-resistant schizophrenia (TRS), dividing the sample into early-onset (N = 21) and adult-onset TRS (N = 20). Previous studies did not differentiate between early- (onset 13-18 years) and adult-onset (>18 years at formal diagnosis of schizophrenia) TRS. METHODS: We evaluated cross-sectionally 41 TRS patients (26 male and 15 female) and 20 matched healthy controls (HCs) with psychopathological and cognitive testing prior to participating in brain imaging scanning using magnetic resonance spectroscopy and diffusion tensor imaging to determine the relationship between their symptoms and their glutamate levels and white matter integrity. RESULTS: TRS patients scored lower than HCs on all cognitive domains; early-onset patients performed better than adult-onset patients only on the Symbol Coding domain. TRS correlated with symptom severity, especially negative symptoms. Glutamate levels and glutamate/creatine were increased in anterior cingulate cortex. Diffusion tensor imaging showed low fractional anisotropy in TRS patients in specific white matter tracts compared to HCs (bilateral anterior thalamic radiation, cortico-spinal tract, forceps minor, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus, and right uncinate fasciculus). CONCLUSIONS: We identified specific magnetic resonance spectroscopy and diffusion tensor imaging alterations in TRS patients. Adult-onset TRS differed little from early-onset TRS on most measures; this points to alterations being present since the outset of schizophrenia and may constitute a biological signature of treatment-resistance.

Developmental trajectories in psychiatric disorders: does substance/alcohol use moderate the effects of affective temperaments as moderators of age at onset? A study in post-acute, hospitalized patients with psychotic or DSM-5 bipolar or major depressive disorders.

BACKGROUND: Age-at-onset (AAO) affects psychiatric disorder outcome; substance (SUDs) or alcohol use disorders (AUDs) may influence their onset. Affective temperaments may affect early AAO and drug-use proneness. Objectives: To investigate whether SUD/AUD moderated temperamental effects in determining AAO of mental disorders. Methods: We included 300 post-acute inpatients with schizophrenia-spectrum and other psychotic (SSOPDs), major depressive (MDD) or bipolar (BD) disorders (168 men; mean age, 40.63 years ± 11.82 men, 43.21 years ± 12.69 women) with (N = 110) or without (N = 190) SUD/AUD. Patients completed cross-sectionally TEMPS-A. We carried moderation analysis with each regression-significant TEMPS temperament as independent variable, SUD/AUD presence/absence as dichotomous moderator, and AAO as dependent variable. Significance was set at p < 0.05. Results: AAO was lower in patients with SUD/AUD diagnosis than in patients without (23.74 ± 10.09 vs. 27.73 ± 10.35, respectively, p = 0.001, η2 = 0.034). SUD/AUD patients scored higher on the hyperthymic (10.22 ± 4.08, p < 0.001, η2 = 0.069) and irritable (8.26 ± 4.69, p < 0.01, η2 = 0.026) temperaments than nonSUD/AUD patients. Moderation analysis showed only direct effects of irritable (ß = -0.55, p < 0.005) and hyperthymic (ß = -0.95, p < 0.001) temperaments on AAO and no significant SUD/AUD and interaction effects. Limitations. Cross-sectional design. Conclusions: When irritable and hyperthymic traits prevail over other temperaments, AAO is earlier in SSOPDs, MDD, and BD. SUD/AUD presence/absence does not moderate the relationship between temperament and AAO.

Vortioxetine vs. Other Antidepressants in Patients with Major Depressive Episode With or Without Substance Use Disorder.

BACKGROUND: Major Depressive Episodes (MDEs) may characterise many psychiatric disorders. Its pharmacotherapy is laid with unmet needs, rendering the testing of new drugs necessary. OBJECTIVE: To compare the effects of vortioxetine with those of other antidepressants (OADs) in a 1-year naturalistic setting. METHODS: We included 126 adult patients with anMDE in the course of major depressive (MDD), bipolar (BD), or schizophrenia spectrum disorders (SSOPDs), with or without substance use disorder (SUD), who received 5-20 mg/day oral vortioxetine, and compared them with 100 patients receiving OADs at baseline and after 1, 3, 8, and 12 months on their scores on the MADRS, the CGIS, the 24-item BPRS, the YMRS, the Hamilton Anxiety Rating Scale, a Visual Analogue Scale for craving, the Columbia-Suicide Severity Rating Scale, and the WHOQOL-BREF. RESULTS: Patients on vortioxetine improved similarly to those on OADs on all measures, independently from having or not a comorbid SUD. However, they improved with time better than their OADcounterparts if affected by BD or SSOPDs, but not MDD, on the CGI-S, BPRS depression, anxiety, and manic symptoms. SUD hampered the response of anxiety to treatment. Men improved on depression with time better than women. CONCLUSION: MDEs responded to vortioxetine similarly to OADs by improving in depression, general psychopathology, anxiety, suicidal thinking, and quality-of-life, independently from SUD comorbidity. MDEs of patients with BD or SSOPDs on vortioxetine responded better than that of patients on OADs. Clinical Trial Registration No. 17354N.

Aripiprazole Long-Acting Injection During First Episode Schizophrenia-An Exploratory Analysis.

Background: Long-acting injectable (LAI) aripiprazole was found to be efficacious in schizophrenia. In common clinical practice, the use of LAIs is often restricted to chronic patients with frequent relapses and poor adherence. Recently, some investigators advanced the idea of early LAI use also in young people with schizophrenia at their first psychotic episode (FEP). Objective: Our study aimed to assess the effect of LAI aripiprazole once monthly (AOM) in the treatment of FEP in patients aged 18-26 years. Methods: We included 50 patients with DSM-5 schizophrenia as assessed with SCID, and used the Clinical Global Impressions Scale-Severity of Illness (CGI-S) and the Positive and Negative Syndrome Scale (PANSS) to assess symptom severity and the World Health Organization Quality of Life (WHOQOL), the Short Form Health Survey (SF-36) and the Personal and Social Performance Scale (PSP) to assess quality of life (QoL) and global health perception at baseline and 3, 6, 9, and 12 months after the first AOM injection. Results: AOM was associated with a progressive improvement, compared to baseline, of both positive (p < 0.001) and negative (p < 0.001) symptoms and in general psychopathology (p < 0.001) and decrease in global severity (p < 0.001). We also observed progressive improvement in QoL and social and personal functioning. Treatment adherence was 78% at study endpoint. Our results support that AOM may improve psychotic symptoms, QoL and social functioning in young FEP patients. Further studies should compare AOM to its oral formulation in the treatment of young patients with schizophrenia at the outset of their illness.

Head-to-head comparison of 1-year aripiprazole long-acting injectable (LAI) versus paliperidone LAI in comorbid psychosis and substance use disorder: impact on clinical status, substance craving, and quality of life.

BACKGROUND: To overcome nonadherence in patients with psychosis switch to long-acting injectable (LAI) antipsychotic formulations is adopted. Most oral versus LAI comparisons showed similar antipsychotic responses. Psychoses often overlap with substance use disorder (SUD). Head-to-head LAI comparisons have hitherto focused only on non-comorbid populations. OBJECTIVE: The objective of this study was to compare two LAIs, administered for 12 months, in initially hospitalized patients with psychosis comorbid with SUD in their clinical and quality of life (QoL) outcomes. PATIENTS AND METHODS: Inpatients were recruited during 2016 and switched randomly to 400 mg intramuscular aripiprazole monohydrate (AM) (N=50) or to 100 mg intramuscular paliperidone palmitate (PP) once-monthly (N=51); patients were discharged and followed up for 12 months. Patients were rated at baseline and after 1 year through the Clinical Global Impression scale - severity (CGIs), substance craving intensity was rated through a visual analog scale for substance craving, and QoL through the World Health Organization (WHOQOL-BREF) scale. We addressed confounders with backward stepwise logistic regression and three-way analysis of variance. RESULTS: PP were older and had more cases of schizophrenia spectrum and less bipolar disorders than AM, but AM had a stronger craving for substances at baseline. Both LAIs were associated with significant improvements in all outcomes, with AM displaying stronger effect sizes than PP. The two groups did not differ on baseline WHOQOL-BREF scores in any domain, but at the 1-year follow-up, AM fared better on all domains. The two groups did not differ in final severity, but PP scored higher than AM in craving at the 1-year endpoint.Limitation: The CGIs is not a refined tool for severity and the substance craving may be subject to recall bias. CONCLUSION: 1-year AM and PP was followed by improved clinical status and QoL and reduced substance craving in a population with psychosis and SUD comorbidity. AM, compared to PP, improved craving and QoL at the 1-year follow-up.

The problem of overcontrol: Perfectionism, emotional inhibition, and personality disorders.

BACKGROUND AND AIMS: Some individuals with Personality Disorders (PD), particularly of a non-Borderline type, present with difficulties relating to over-control of cognitions, emotion and behavior, perfectionistic traits, and impaired social interactions. The current study sought to evaluate the strength of association, and interactions of both emotional inhibition and perfectionism in PD's, after controlling for symptoms and interpersonal problems. METHOD: We recruited a sample of 578 treatment seeking outpatients. Diagnosis of PD was made with the SCID-II. Individual's completed measures of perfectionism (Frost-MPS), Emotional Inhibition (EIS), Depression (BDI-II), Anxiety (STAI-Y), Global symptoms (SCL-90-R), and interpersonal problems (IIP-32). RESULTS: Perfectionism was related to interpersonal problems, to the majority of PD symptomatology and to PD severity via number of SCID-II criteria met. Emotional inhibition was linked to symptoms and interpersonal problems as well as with avoidant, dependent, depressive and paranoid PDs; and with overall PD Severity. Inhibition and perfectionism were correlated with each other. Both variables predicted PD above and beyond other variables assessed. Mediation modeling demonstrated that the effect of emotional inhibition on PD severity was fully mediated by perfectionism and interpersonal problems. CONCLUSIONS: Psychological mechanisms of overcontrol are a maintaining factor in many PDs. Both perfectionism and emotional inhibition impact on a broad range of PDs and there is an urgent need for research into these processes, and to adapt psychological interventions to consider these factors.

Emotion dysregulation, symptoms, and interpersonal problems as independent predictors of a broad range of personality disorders in an outpatient sample.

Emotion dysregulation (ED) is considered a hallmark of borderline personality disorder and is prominent in other personality disorders (PDs). Its presence and contribution to personality pathology need to be explored in the whole range of PDs. In this study, we investigated the association of ED with the whole range of PD traits, symptoms, and interpersonal problems and then investigated whether ED had a unique contribution in predicting the different PDs. A sample of 478 treatment-seeking outpatients was interviewed with the SCID-II. The patients were then tested for symptoms (SCL-90-R), interpersonal problems (IIP-32), and ED (DERS). RESULTS: ED correlated with the large majority of PDs and with symptoms and interpersonal problems. Regression showed how ED explained a unique part of the variance for many PDs. ED appears to be a relevant feature of pathology in many PDs; with replication, it can be considered a treatment target in this population. PRACTITIONER POINTS: Emotion dysregulation is present in many personality disorders. Emotion dysregulation is not just explained by heightened symptoms and interpersonal problems in personality disorders. Emotion dysregulation could be considered a treatment target in personality disorders other than borderline.