Aripiprazole and Risperidone Present Comparable Long-Term Metabolic Profiles: Data From a Pragmatic Randomized Controlled Trial in Drug-Naïve First-Episode Psychosis

Objective: Aripiprazole and risperidone are 2 of the most used second-generation antipsychotics (SGAs) worldwide. Previous evidence shows a similar effect of these SGAs on weight and metabolic changes in the short term. However, a longer period is necessary for a better assessment of the SGA´s metabolic profile. We aimed to compare the long-term (1-year) metabolic profile of these 2 antipsychotics on a sample of drug-naïve first episode-psychosis (FEP) patients. Methods: A total 188 drug-naïve patients, suffering from a first episode of non-affective psychosis (FEP), were randomly assigned to treatment with either aripiprazole or risperidone. Weight and glycemic/lipid parameters were recorded at baseline and after 1-year follow-up. Results: We observed significant weight increments in both groups (9.2 kg for aripiprazole and 10.5 kg for risperidone) after 1 year of treatment. Despite this, weight and body mass index changes did not significantly differ between treatment groups (P > .05). Similarly, both treatment groups presented similar metabolic clinical impact with a comparable increase in the proportion of participants meeting criteria for metabolic disorders such as obesity or hypercholesterolemia, but not for metabolic syndrome (?9.2% vs ?4.3%) or hypertriglyceridemia (?21.9% vs ?8.0%), where aripiprazole showed worse outcomes than risperidone. Conclusion: This study shows that aripiprazole and risperidone share a similar long-term metabolic profile. After 1 year of antipsychotic treatment, drug-naïve FEP patients in both treatment groups presented a significant increase in weight and metabolic changes, leading to a greater prevalence of metabolic disorders

Aripiprazole vs Risperidone Head-to-Head Effectiveness in First-Episode Non-Affective-Psychosis: A 3-Month Randomized, Flexible-Dose, Open-Label Clinical Trial

Background: Antipsychotic choice for the acute phase of a first episode of psychosis (FEP) is of the utmost importance since it may influence long-term outcome. However, head-to-head comparisons between second-generation antipsychotics remain scarce. The aim of this study was to compare the effectiveness in the short term of aripiprazole and risperidone after FEP outbreak. Methods: From February 2011 to October 2018, a prospective, randomized, open-label study was undertaken. Two hundred-sixty-six first-episode drug-naïve patients were randomly assigned to aripiprazole (n = 136) or risperidone (n = 130) and followed-up for 12 weeks. The primary effectiveness measure was all-cause treatment discontinuation. In addition, an analysis based on intention-to-treat principle was conducted to assess clinical efficacy. Results: The overall dropout rate at 12 weeks was small (6.39%). Effectiveness measures were similar between treatment arms as treatment discontinuation rates (? 2 = 0,409; P = .522), and mean time to all-cause discontinuation (log rank ? 2 = -1.009; P = .316) showed no statistically significant differences. Despite no statistically significant differences between groups regarding clinical efficacy, aripiprazole required higher chlorpromazine equivalent dosage (? 2 = 2.160; P = .032) and extended mean time (W = 8183.5; P = .008) to reach clinical response. Sex-related adverse events and rigidity were more frequent in the risperidone group, whereas sialorrhea was on the aripiprazole group. Conclusions: No differences regarding effectiveness were found between aripiprazole and risperidone for the short-phase treatment of FEP. Despite the importance of efficacy during this phase, differences in side effect profiles and patient's preferences are essential factors that may lead clinical decisions for these patients

Expression and Functionality Study of 9 Toll-Like Receptors in 33 Drug-Naïve Non-Affective First Episode Psychosis Individuals: A 3-Month Study

Toll-like receptors (TLRs) are a pivotal component of the innate immune system that seem to have a role in the pathogenesis of psychosis. The purpose of this work was to compare the expression and functionality of 9 TLRs in three peripheral blood mononuclear cells (PBMCs) (monocytes, B cells, and T cells) between 33 drug-naïve first-episode psychosis (FEP) individuals and 26 healthy volunteers, at baseline and after 3-month of antipsychotic treatment. The expression of TLRs 1?9 were assessed by flow cytometry. For the assessment of the TLR functionality, cells collected in sodium heparin tubes were polyclonally stimulated for 18 h, with different agonists for human TLR1?9. The results of our study highlight the role that TLR5 and TLR8 might play in the pathophysiology of psychosis. We found a lower expression of these receptors in FEP individuals, regarding healthy volunteers at baseline and after 3-month of treatment on the three PBMCs subsets. Most TLRs showed a lower functionality (especially reduced intracellular levels of TNF-?) in patients than in healthy volunteers. These results, together with previous evidence, suggest that individuals with psychosis might show a pattern of TLR expression that differs from that of healthy volunteers, which could vary according to the intensity of immune/inflammatory respons

Longitudinal trajectories in negative symptoms and changes in brain cortical thickness: 10-year follow-up study

Background Understanding the evolution of negative symptoms in first-episode psychosis (FEP) requires long-term longitudinal study designs that capture the progression of this condition and the associated brain changes. Aims To explore the factors underlying negative symptoms and their association with long-term abnormal brain trajectories. Method We followed up 357 people with FEP over a 10-year period. Factor analyses were conducted to explore negative symptom dimensionality. Latent growth mixture modelling (LGMM) was used to identify the latent classes. Analysis of variance (ANOVA) was conducted to investigate developmental trajectories of cortical thickness. Finally, the resulting ANOVA maps were correlated with a wide set of regional molecular profiles derived from public databases. Results Three trajectories (stable, decreasing and increasing) were found in each of the three factors (expressivity, experiential and attention) identified by the factor analyses. Patients with an increasing trajectory in the expressivity factor showed cortical thinning in caudal middle frontal, pars triangularis, rostral middle frontal and superior frontal regions from the third to the tenth year after the onset of the psychotic disorder. The F-statistic map of cortical thickness expressivity differences was associated with a receptor density map derived from positron emission tomography data. Conclusions Stable and decreasing were the most common trajectories. Additionally, cortical thickness abnormalities found at relatively late stages of FEP onset could be exploited as a biomarker of poor symptom outcome in the expressivity dimension. Finally, the brain areas with less density of receptors spatially overlap areas that discriminate the trajectories of the expressivity dimension.Funding: This work was supported by the Instituto de Salud Carlos III (PI14/00639 and PI14/00918) and Fundación Instituto de Investigación Marqués de Valdecilla (NCT0235832 and NCT02534363). M.C.-R. acknowledges funding support from the Consejería de Salud y Familias (Junta de Andalucía) 2020 grant, which covers his salary (RH-0081 2020). R.R.-G. is funded by the EMERGIA Junta de Andalucía programme (EMERGIA20_00139) and the Plan Propio of the University of Seville

Understanding sex differences in long-term outcomes after a first episode of psychosis

While sex differences in schizophrenia have long been reported and discussed, long-term sex differences in outcomes among first episode of psychosis (FEP) patients in terms of the efficacy of Early Intervention Services (EIS) has been an under-explored area. A total of 209 FEP patients (95 females and 114 males) were reassessed after a time window ranging from 8 to 16 years after their first contact with an EIS program (PAFIP) that we will call the 10-year PAFIP cohort. Multiple clinical, cognitive, functioning, premorbid, and sociodemographic variables were explored at 1-year, 3-year and 10-year follow-ups. At first contact, females were older at illness onset, had higher premorbid adjustment and IQ, and were more frequently employed, living independently, and accompanied by a partner and/or children. Existence of a schizophrenia diagnosis, and cannabis and alcohol consumption were more probable among men. During the first 3 years, women showed a significantly better response to minimal antipsychotic dosages and higher rates of recovery than men (50% vs. 30.8%). Ten years later, more females continued living independently and had partners, while schizophrenia diagnoses and cannabis consumption continued to be more frequent among men. Females also presented a lower severity of negative symptoms; however, functionality and recovery differences did not show significant differences (46.7% vs. 34.4%). Between the 3- and 10-year follow-up sessions, an increase in dosage of antipsychotics was observed. These results suggest that the better outcomes seen among women during the first 3 years (while they were treated in an EIS) were in the presence of more favourable premorbid and baseline characteristics. After an average period of 10 years, with the only difference being in negative symptoms course, outcomes for women approximated those of men, drawing particular attention to the increase in dosage of antipsychotic medication once FEP patients were discharged from the EIS program towards community-based services. These findings help to pose the question of whether it is advisable to target sexes and lengthen EIS interventions

Multidisciplinary consensus on the therapeutic recommendations for iatrogenic hyperprolactinemia secondary to antipsychotics

Hyperprolactinemia is an underappreciated/unknown adverse effects of antipsychotics. The consequences of hyperprolactinemia compromise therapeutic adherence and can be serious. We present the consensus recommendations made by a group of experts regarding the management of antipsychotic-induced hyperprolactinemia. The current consensus was developed in 3 phases: 1, review of the scientific literature; 2, subsequent round table discussion to attempt to reach a consensus among the experts; and 3, review by all of the authors of the final conclusions until reaching a complete consensus. We include recommendations on the appropriate time to act after hyperprolactinemia detection and discuss the evidence on available options: decreasing the dose of the antipsychotic drug, switching antipsychotics, adding aripiprazole, adding dopaminergic agonists, and other type of treatment. The consensus also included recommendations for some specific populations such as patients with a first psychotic episode and the pediatric-youth population, bipolar disorder, personality disorders and the elderly population

Estudio longitudinal a tres años de la evolución clínica en pacientes que, tras un único episodio de psicosis no afectiva, han alcanzado una recuperación completa mantenida y deciden retirar la medicación antipsicótica

RESUMEN: Objetivo: Continúa poco claro cuándo se puede retirar el tratamiento antipsicótico en pacientes que se han recuperado de un primer episodio de psicosis. Nuestro objetivo era evaluar el riesgo de recaída en los tres años tras la retirada de medicación en pacientes con una recuperación completa tras un único episodio psicótico. Método: Pacientes que cumplían criterios de recuperación completa tras un PEP. 46 individuos fueron incluidos en el grupo de discontinuación y 22, que continuaron tratamiento en el de mantenimiento. Medidas de resultado fueron la tasa de recaída a los 18 y 36 meses y el tiempo hasta la recaída. Resultados: La tasa de recaída fue 67.4% en el grupo de discontinuación y 31.8% en el de mantenimiento. El tiempo medio hasta la recaída fue 209 y 608 días, respectivamente. (Log Rank=10.106; p=0.001). Al comparar el grupo que recayó (N=38) con aquellos que continuaron asintomáticos a los tres años (N=30), se encontraron diferencias significativas en las puntuaciones totales de la SANS,CGI y DAS. Conclusiones: La discontinuación del tratamiento antipsicótico en pacientes que han alcanzado una recuperación completa tras un primer episodio de psicosis se asocia a mayor riesgo de recaída. Los individuos que recayeron tuvieron peor status funcional a los tres años.ABSTRACT: Objective: The timing of antipsychotic discontinuation in patients who have fully recovered from their initial episode of psychosis remains unclear. We aimed to evaluate the risk of symptoms recurrence during three years after antipsychotic discontinuation in functionally recovered first-episode of psychosis patients. Method: Functionally recovered FEP individuals meeting the inclusion criteria of clinical and functional recovery were eligible. 46 individuals who discontinue medication were included in the discontinuation group, 22 who continue the antipsychotic medication in the maintenance group. Primary outcome measures were relapse rate at 18 and 36 months and time to relapse. Results: The rates of relapse were 67.4% in the discontinuation and 31.8% in the maintenance group. The mean time to relapse was 209 and 608 days, respectively (Log Rank=10.106; p=0.001). When the group of relapsed individuals (N=38), was compared to those who remained asymptomatic after 3 years (N=30), there were significant differences in total scores of SANS, CGI, and DAS. Conclusions: Antipsychotic treatment discontinuation in individuals who had accomplished a functional recovery after a single psychotic episode was associated with a high risk of symptom recurrence. Relapsed individuals had lower functional status after 3 years

Current Data on and Clinical Insights into the Treatment of First Episode Nonaffective Psychosis: A Comprehensive Review

<p><b>Article full text</b></p> <p><br></p> <p>The full text of this article can be found here<b>. </b><a href="https://link.springer.com/article/10.1007/s40120-016-0050-8">https://link.springer.com/article/10.1007/s40120-016-0050-8</a></p><p></p> <p><br></p> <p><b>Provide enhanced content for this article</b></p> <p><br></p> <p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p> <p><br></p> <p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p> <p><br></p> <p>Other enhanced features include, but are not limited to:</p> <p><br></p> <p>• Slide decks</p> <p>• Videos and animations</p> <p>• Audio abstracts</p> <p>• Audio slides</p

Cost of relapse management in patients with schizophrenia in Italy and Spain: comparison between lurasidone and quetiapine XR

Background and Objective: Schizophrenia is a low-prevalence mental disorder with a global age-standardized prevalence of 21 million people (2016). Second-generation antipsychotics (lurasidone and quetiapine XR) are recommended as the first-line treatment for schizophrenia. It is interesting to investigate how the results of clinical studies translate into direct medi-cal costs. The objective of this analysis was to assess the direct medical costs related to pharmaceutical treatments and the management of relapses in patients affected with schizophrenia treated with lurasidone (74 mg) vs quetiapine XR (300 mg) assuming the Italian and Spanish National Health Service perspective. Methods: A health economic model was developed based on a previously published model. The analysis considered direct medical costs related to the pharmacological therapies and inpatient or outpatient management of relapses (direct medical costs referred to 2019). The probability of relapses and related costs were derived from two systematic reviews. A determin-istic sensitivity analysis was implemented to test the robustness of the results. Results: The use of lurasidone (74 mg) compared with quetiapine XR (300 mg) would lead to a reduction in direct medical costs in Italy and Spain, with a lower cost per patient of − 163.7 € (− 9.0%) and − 327.2 € (− 22.7%), respectively. In detail, it would lead to an increase in the cost of therapy of + 53.8% and of + 30.5% in Italy and Spain, respectively, to a decrease in the cost of relapses with hospitalization of − 135.7%, and to an increase in the cost of relapses without hospitalization of + 24.5%. Conclusions: The use of lurasidone (74 mg) for the treatment of patients affected with schizophrenia, compared with quetia-pine XR (300 mg), would be a cost-saving strategy in the two contexts investigated assuming the National Health Service point of view

Valor predictivo de prolactina en los primeros episodios de psicosis durante el seguimiento a diez años

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