This post-hoc study was aimed at assessing whether disease severity was higher in a sample of Treatment Resistant Schizophrenia patients (TRS) compared to schizophrenia patients responsive to antipsychotics (non-TRS). Determinants of disease severity were also investigated in these groups. Eligible patients were screened by standardized diagnostic algorithm to categorize them as TRS or non-TRS. All patients underwent the following assessments: CGI-S; PANSS; DAI; NES; a battery of cognitive tests. Socio-demographic and clinical variables were also recorded. TRS patients exhibited significantly higher disease severity and psychotic symptoms, either as PANSS total score or subscales' scores. A preliminary correlation analysis ruled out clinical and cognitive variables not associated with disease severity in the two groups. Hierarchical linear regression showed that negative symptoms were the clinical variable explaining the highest part of variation in disease severity in TRS, while in non-TRS patients PANSS-General Psychopathology was the variable explaining the highest variation. Mediation analysis showed that negative symptoms mediate the effects of verbal fluency dysfunctions and high-level neurological soft signs (NSS) on TRS' disease severity. These results show that determinants of disease severity sharply differ in TRS and non-TRS patients, and let hypothesize that TRS may stem from cognitive disfunctions and putatively neurodevelopmental aberrations.

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Aim Early age at schizophrenia onset (EOS) has been associated with a worse clinical course, although previous studies reported substantial heterogeneity. Despite the relevance of the subject, the relationship between the age of onset and treatment resistant schizophrenia (TRS) is less clear. Methods We screened 197 non‐affective psychotic patients. Of these, 99 suffered from schizophrenia and were putative TRS and were included in a prospective 4‐to‐8‐week trial to assess their response to antipsychotics. According to status (TRS/nonTRS) and age‐at‐onset (early: ≤18 years, EOS; adult: >18 years, adult onset schizophrenia [AOS]) patients were subdivided in EOS‐TRS, EOS‐nonTRS, AOS‐TRS, AOS‐nonTRS. Multiple clinical variables were measured and compared by analysis of covariance (ANCOVA), using age as a covariate. Two‐way analysis of variance (ANOVA) was used to assess whether significant differences were attributable to TRS status or age‐at‐onset. Results The rate of TRS patients was significantly higher in EOS compared to AOS. At the ANCOVA, EOS‐TRS had significantly worse clinical, cognitive, and psychosocial outcomes compared to the other groups. Overall, EOS‐TRS were more impaired than EOS‐nonTRS, while significant differences with AOS‐TRS were less consistent, albeit appreciable. Two‐way ANOVA demonstrated that, in the majority of the investigated variables, the significant differences among groups were attributable to the TRS status effect rather than to age‐at‐onset or combined effects. Conclusions These results suggest that refractoriness to antipsychotics may be strongly linked to the early onset of psychotic symptoms, possibly as a result of common neurobiology.

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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., prior to suffering Covid-19–related trauma and after suffering such 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 a part of them, a month of hospitalisation. Scores on the MADRS, Ham-A, BPRS, VAS-crav and WHOQOL-BREF were compared drug-wise and gender-wise with Student’s t test for continuous variables and χ2 for categorical variables. Result: 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, symptoms worsening was 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 after Covid-19 trauma in patients with MDE, with vortioxetine showing a small advantage. No differences between vortioxetine, sertraline and trazodone were found as concerns the need for hospitalisation.

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 a MDE 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 CGI-S, 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 OADs counterparts 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.

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