Clozapine and paliperidone palmitate antipsychotic combination in treatment-resistant schizophrenia and other psychotic disorders: A retrospective 6-month mirror-image study

Background: Around 30% of patients with schizophrenia are considered treatment resistant (TRS). Only around 40% of TRS patients respond to clozapine. Long acting injectable antipsychotics could be a useful augmentation strategy for nonresponders. Methods: We conducted a multicenter, observational, naturalistic, retrospective, 6-month mirror-image study to evaluate the efficacy and tolerability of clozapine and paliperidone palmitate association in 50 patients with TRS and other psychotic disorders. Clinical outcomes and side effects were systematically assessed. Results: Six months after starting the combined treatment, participants showed a significant relief of symptoms, decreasing the Brief Psychiatric Rating Scale total score from 18.32 ± 7.71 to 7.84 ± 5.16 (p < 0.001). The number of hospitalizations, the length of hospital stays and the number of visits to emergency services also decreased, while an increase of the functionality was observed (Personal and Social Performance total score increased from 46.06 ± 118.7 to 60.86 ± 18.68, p < 0.001). There was also a significant decrease in the number and severity of side effects with the combination therapy, decreasing the Udvalg for Kliniske Undersogelser total score from 10.76 ± 8.04 to 8.82 ± 6.63 (p = 0.004). Conclusions: This study provides the first evidence that combining clozapine with paliperidone palmitate in patients with TRS and other psychotic disorders could be effective and safe, suggesting further research with randomized controlled trials of augmentation strategies for clozapine nonresponder patients. Policy Significance Statement: Patients with psychotic disorders such as schizophrenia show a variable response to antipsychotic treatments. Around 30% of patients are considered treatment resistant, indicated by insufficient symptom control to at least two different drugs. In these resistant cases, clozapine should be indicated, as it has shown to be superior to other options. However, only 40% of patients respond to clozapine, being necessary to establish which treatments could best potentiate clozapine action. Combining clozapine with long acting injectable antipsychotics, and particularly paliperidone palmitate, could be a useful strategy. We conducted a multicenter study of 50 patients with treatment-resistant schizophrenia and other psychotic disorders comparing the efficacy and tolerability in the 6 month-period prior and after starting the clozapine and paliperidone palmitate association. Our study suggests that this combination could be effective and safer, laying the groundwork for future clinical trials with this combination

Identifying pathways between psychiatric symptoms and psychosocial functioning in the general population

The present study aims to identify pathways between psychiatric network symptoms and psychosocial functioning and their associated variables among functioning clusters in the general population. A cross-sectional web-based survey was administered in a total of 3,023 individuals in Brazil. The functioning clusters were derived by a previous study identifying three different groups based on the online Functioning Assessment Short Test. Networking analysis was fitted with all items of the Patient-Reported Outcomes Measurement Information System for depression and for anxiety (PROMIS) using the mixed graphical model. A decision tree model was used to identify the demographic and clinical characteristics of good and low functioning. A total of 926 (30.63%) subjects showed good functioning, 1,436 (47.50%) participants intermediate functioning, and 661 (21.86%) individuals low functioning. Anxiety and uneasy symptoms were the most important nodes for good and intermediate clusters but anxiety, feeling of failure, and depression were the most relevant symptoms for low functioning. The decision tree model was applied to identify variables capable to discriminate individuals with good and low functioning. The algorithm achieved balanced accuracy 0.75, sensitivity 0.87, specificity 0.63, positive predictive value 0.63 negative predictive value 0.87 (p<0.001), and an area under the curve of 0.83 (95%CI:0.79–0.86, p<0.01). Our results show that individuals who present psychological distress are more likely to experience poor functional status, suggesting that this subgroup should receive a more comprehensive psychiatric assessment and mental health care

Toward precision psychiatry in bipolar disorder : staging 2.0

Personalized treatment is defined as choosing the “right treatment for the right person at the right time.” Although psychiatry has not yet reached this level of precision, we are on the way thanks to recent technological developments that may aid to detect plausible molecular and genetic markers. At the moment there are some models that are contributing to precision psychiatry through the concept of staging. While staging was initially presented as a way to categorize patients according to clinical presentation, course, and illness severity, current stagingmodels integratemultiple levels of information that can help to define each patient’s characteristics, severity, and prognosis in a more precise and individualized way. Moreover, staging might serve as the foundation to create a clinical decision-making algorithm on the basis of the patient’s stage. In this review we will summarize the evolution of the bipolar disorder staging model in relation to the new discoveries on the neurobiology of bipolar disorder. Furthermore, we will discuss how the latest and future progress in psychiatry might transform current staging models into precision staging models

Self-reported neurocognitive symptoms during COVID-19 lockdown and its associated factors in a sample of psychiatric patients. Results from the BRIS-MHC study

Lockdown caused by COVID-19 pandemic has a negative impact on mental health. The aim was to assess self-reported neurocognitive symptoms during the lockdown and identify associated vulnerable and protective factors in a sample of psychiatric patients in a Spanish population.These results are part of the Barcelona ResIlience Survey for Mental Health COVID-19 (BRISMHC) project. Neurocognitive symptoms were assessed through an online survey considering the five items that represented self-reported neurocognitive complaints. We split the sample into two groups based on the severity of the self-reported neurocognitive complaints: intact cognitive function/mild cognitive impairment (CI-) and moderate/severe cognitive impairment (CI+). Univariate analyses were used to compare both groups in terms of sociodemographic and clinical variables. Multiple logistic regression models were carried out to identify clinical variables and coping strategies associated with neurocognitive symptoms. 198 patients with different psychiatric diagnoses were included in this study. One hundred seventeen patients were classified in the CI- group and 81 in the CI+ group. Depressive symptoms and negative psychotic-like symptoms were vulnerable factors for neurocognitive impairment. Coping strategies of performing physical activity, carrying out relaxing activities and maintaining a routine were protective factors against cognitive impairment. Lockdown situation negatively impact on neurocognitive function. Psychopathological symptoms and coping strategies were associated with neurocognitive symptoms during lockdown in subjects with psychiatric illness. The early treatment of psychopathological symptoms in psychiatric patients and promoting coping strategies during lockdown should be considered an intervention strategy against cognitive impairment

Toward precision psychiatry in bipolar disorder: staging 2.0

Personalized treatment is defined as choosing the "right treatment for the right person at the right time." Although psychiatry has not yet reached this level of precision, we are on the way thanks to recent technological developments that may aid to detect plausible molecular and genetic markers. At the moment there are some models that are contributing to precision psychiatry through the concept of staging. While staging was initially presented as a way to categorize patients according to clinical presentation, course, and illness severity, current staging models integrate multiple levels of information that can help to define each patient's characteristics, severity, and prognosis in a more precise and individualized way. Moreover, staging might serve as the foundation to create a clinical decision-making algorithm on the basis of the patient's stage. In this review we will summarize the evolution of the bipolar disorder staging model in relation to the new discoveries on the neurobiology of bipolar disorder. Furthermore, we will discuss how the latest and future progress in psychiatry might transform current staging models into precision staging models

The effect of family environment and psychiatric family history on psychosocial functioning in first-episode psychosis at baseline and after 2 years

Abstract The aim of the present study was to evaluate the contribution of family environment styles and psychiatric family history on functioning of patients presenting first-episode psychosis (FEP). Patients with FEP and healthy controls (HC) were assessed at baseline and after 2 years. The Functional Assessment Short Test (FAST) was used to assess functional outcome and the Family Environment Scale (FES) to evaluate family environment. Linear regressions evaluated the effect that family environment exerts on functioning at baseline and at 2-year follow-up, when FEP patients were diagnosed according to non-affective (NA-PSYCH) or affective psychoses (APSYCH). The influence of a positive parents' psychiatric history on functioning was evaluated through one-way between-groups analysis of covariance (ANCOVA) models, after controlling for family environmental styles. At baseline, FEP patients presented moderate functioning impairment, significantly worse than HC (28.65±16.17 versus 3.25±7.92; p<0.001, g = 1.91). At 2-year follow-up, the functioning of NA-PSYCH patients was significantly worse than in A-PSYCH (19.92±14.83 versus 12.46±14.86; p = 0.020, g = 0.50). No specific family environment style was associated with functioning in FEP patients and HC. On the contrary, a positive psychiatric father's history influenced functioning of FEP patients. After 2 years, worse functioning in NA-PSYCH patients was associated with lower rates of active-recreational and achievement orientated family environment and with higher rates of moral-religious emphasis and control. In A-PSYCH, worse functioning was associated with higher rates of conflict in the family. Both family environment and psychiatric history influence psychosocial functioning, with important implications for early interventions, that should involve both patients and caregivers

Resilience and mental health during the COVID-19 pandemic

Background: Resilience is a process that allows recovery from or adaptation to adversities. The aim of this study was to evaluate state resilience during the COVID-19 pandemic in psychiatric patients (PP), unaffected relatives (UR) and community controls (CC). Methods: This study is part of the Barcelona ResIlience Survey for Mental Health COVID-19 (BRIS-MHC) project. Logistic regression models were performed to identify mental health outcomes associated with bad state resilience and predictors of good state resilience. The association between state resilience and specific affective temperaments as well as their influence on the association between depressive symptoms and state resilience were verified. Results: The study recruited 898 participants that took part in the survey. The presence of depressive symptoms was a predictor of bad state resilience in PP (β=0.110, OR=1.117, p=0.028). No specific mental health outcome was associated with bad state resilience in UR and CC. Predictors of good state resilience in PP were having pursued hobbies/conducted home tasks (β=1.261, OR=3.528, p=0.044) and level of organization in the family (β=0.986, OR=2.682, p=0.008). Having a controlling family was inversely associated with good state resilience in CC (β=-1.004, OR=0.367, p=0.012). The association between bad state resilience and depressive symptoms was partially mediated by affective temperaments. Limitations: Participants self-reported their psychiatric diagnoses, their relatives' diagnoses or the absence of a psychiatric disorder, as well as their psychiatric symptoms. Conclusions: Enhancing resilience and coping strategies in the face of the COVID-19 pandemic might have important implications in terms of mental health outcomes

Cortical thinning over two years after first-episode psychosis depends on age of onset

First-episode psychosis (FEP) patients show structural brain abnormalities at the first episode. Whether the cortical changes that follow a FEP are progressive and whether age at onset modulates these changes remains unclear. This is a multicenter MRI study in a deeply phenotyped sample of 74 FEP patients with a wide age range at onset (15-35 years) and 64 neurotypical healthy controls (HC). All participants underwent two MRI scans with a 2-year follow-up interval. We computed the longitudinal percentage of change (PC) for cortical thickness (CT), surface area (CSA) and volume (CV) for frontal, temporal, parietal and occipital lobes. We used general linear models to assess group differences in PC as a function of age at FEP. We conducted post-hoc analyses for metrics where PC differed as a function of age at onset. We found a significant age-by-diagnosis interaction effect for PC of temporal lobe CT (d = 0.54; p = 002). In a post-hoc-analysis, adolescent-onset (≤19 y) FEP showed more severe longitudinal cortical thinning in the temporal lobe than adolescent HC. We did not find this difference in adult-onset FEP compared to adult HC. Our study suggests that, in individuals with psychosis, CT changes that follow the FEP are dependent on the age at first episode, with those with an earlier onset showing more pronounced cortical thinning in the temporal lobe

Influence of clinical and neurocognitive factors in psychosocial functioning after a first episode non-affective psychosis: Differences between males and females

Background: Deficits in psychosocial functioning are present in the early stages of psychosis. Several factors, such as premorbid adjustment, neurocognitive performance, and cognitive reserve (CR), potentially influence functionality. Sex differences are observed in individuals with psychosis in multiple domains. Nonetheless, few studies have explored the predictive factors of poor functioning according to sex in first-episode psychosis (FEP). This study aimed to explore sex differences, examine changes, and identify predictors of functioning according to sex after onset. Materials and methods: The initial sample comprised 588 individuals. However, only adults with non-affective FEP (n = 247, 161 males and 86 females) and healthy controls (n = 224, 142 males and 82 females) were included. A comprehensive assessment including functional, neuropsychological, and clinical scales was performed at baseline and at 2-year follow-up. A linear regression model was used to determine the predictors of functioning at 2-year follow-up. Results: FEP improved their functionality at follow-up (67.4% of both males and females). In males, longer duration of untreated psychosis (β = 0.328, p = 0.003) and worse premorbid adjustment (β = 0.256, p = 0.023) were associated with impaired functioning at 2-year follow-up, while in females processing speed (β = 0.403, p = 0.003), executive function (β = 0.299, p = 0.020) and CR (β = -0.307, p = 0.012) were significantly associated with functioning. Conclusion: Our data indicate that predictors of functioning at 2-year follow-up in the FEP group differ according to sex. Therefore, treatment and preventative efforts may be adjusted taking sex into account. Males may benefit from functional remediation at early stages. Conversely, in females, early interventions centered on CR enhancement and cognitive rehabilitation may be recommended

Cognitive clusters in first-episode psychosis

Impairments in a broad range of cognitive domains have been consistently reported in some individuals with first-episode psychosis (FEP). Cognitive deficits can be observed during the prodromal stage. However, the course of cognitive deficits is still unclear. The aim of this study was to identify cognitive subgroups over time and to compare their sociodemographic, clinical and functional profiles. A total of 114 patients with Schizophrenia Spectrum Disorders were included in the present study. We assessed subjects through psychiatric scales and eight neuropsychological tests at baseline and at two-year follow-up visit. We performed the Partition Around Medoids algorithm with all cognitive variables. Furthermore, we performed a logistic regression to identify the predictors related to the different cognitive clusters at follow-up. Two distinct subgroups were found: the first cluster characterized by cognitive impairment and a second cluster had relatively intact cognition in comparison with norms. Up to 54.7% of patients with cognitive deficits at baseline tended to improve during the first two years of treatment. Patients with intact cognition at follow-up had a higher socioeconomic status, later age of onset, lower negative symptoms and a higher cognitive reserve (CR) at baseline. CR and age of onset were the baseline variables that predicted cognitive impairment. This research allows us to obtain a better understanding of the heterogeneous profile of psychotic disorders. Identifying the characteristics of patients who wil