Trajectories of Symptom Dimensions in Short-Term Response to Antipsychotic Treatment in Patients with a First Episode of Non-Affective Psychosis

Background Trajectory patterns of positive, disorganized and negative dimension symptoms during antipsychotic treatment in drug-naive patients with first-episode psychosis have yet to be examined by using naturalistic data. Method This pragmatic clinical trial randomized 161 drug-naive patients with a first episode of psychosis to olanzapine, risperidone or haloperidol. Patients were assessed with the Scale for the Assessment of Negative Symptoms (SANS) and Positive Symptoms (SAPS) at baseline and at the end of weeks 1, 2, 3, 4 and 6 of antipsychotic treatment. Censored normal models of response trajectories were developed with three dimensions of the SAPS-SANS scores (positive, disorganized and negative) in order to identify the different response trajectories. Diagnosis, cannabis use, duration of untreated psychosis (DUP), smoking and antipsychotic class were examined as possible predictive variables. Results Patients were classified in five groups according to the positive dimension, three groups according to the disorganized dimension and five groups according to the negative dimension. Longer DUPs and cannabis use were associated with higher scores and poorer responses in the positive dimension. Cannabis use was associated with higher scores and poorer responses in the disorganized dimension. Only schizophrenia diagnosis was associated with higher scores and poorer responses in the negative dimension. Conclusions Our results illustrate the heterogeneity of short-term response to antipsychotics in patients with a first episode of psychosis and highlight markedly different patterns of response in the positive, disorganized and negative dimensions. DUP, cannabis use and diagnosis appeared to have a prognostic value in predicting treatment response with different implications for each dimension

Association of gene-enviroment and age of pre-onset cannabis use with age at onset of psychosis in frist-episode patients

Trabajo presentado a la 10ª Reunión anual de la Sociedad Española de Investigación sobre Cannabinoides celebrada en Santander del 26 al 28 de noviembre de 2009.Es conocida la influencia negativa del uso de cannabis sobre el curso y pronóstico de la esquizofrenia. El cannabis es, además, la sustancia de abuso más utilizada en pacientes con esquizofrenia (15%-65%). Sin embargo sólo una pequeña proporción de consumidores de cannabis desarrollan psicosis. Varios estudios han demostrado que el uso de cannabis precede al debut de la psicosis en varios años (entre 4 y 5 ). El inicio precoz del consumo de cannabis en la adolescencia, puede por tanto, estar asociado a un debut precoz de la psicosis, con el consiguiente pronóstico negativo de la enfermedad. Varios polimorfismos de nucleótidoúnico (SNPs) del gen que codifica el receptor CB1 (CNR1; rs806379, rs1535255, rs2023239 y rs1049353) han sido asociados al consumo de drogas o alcohol (Zhang et al., Molecular Psychiatry, 9, 916–931. 2004, Schmidtetal., 2002 Drug and Alcohol Dependence, 65, 221–224) Variaciones en el gen de la triptófano hidroxilasa se han asociado con un mayor riesgo de psicosis (LiD, HeL: Hum Genet 2006). Finalmente, algunos de los SNPs en los receptores de la serotonina se han asociado con diversos trastornos psiquiátricos como la esquizofrenia o la depresión, sin embargo, los resultados de estos estudios de asociación genética han mostrado resultados conflictivos.Peer Reviewe

Data regarding active psychosis and functional outcome, among other clinical variables, during early phases of the illness in first-episode psychosis in the PAFIP 10-year follow-up program

This article describes data related to the research study entitled ?Duration of active psychosis during early phases of the illness and functional outcome: The PAFIP 10-year follow-up study.? [1]. We present data concerning the clinical and sociodemographic characteristics of a sample of drug-naïve patients with a first episode of non-affective psychosis. The dataset was obtained from a 3-year longitudinal intervention program as part of an ongoing 10-year epidemiological study. The tables and figure shown present the data from the analysis between the active psychosis (presence of positive psychotic symptoms), among other sociodemographic and clinical predictor variables, recorded during the 3-year longitudinal intervention program and the evaluation of the functional outcome (social functioning and functional recovery) present at the 10-year mark. The data explores how those early parameters could influence long-term outcome

Antipsychotic Treatment Effectiveness in First Episode of Psychosis: PAFIP 3-Year Follow-Up Randomized Clinical Trials Comparing Haloperidol, Olanzapine, Risperidone, Aripiprazole, Quetiapine, and Ziprasidone

Background: Different effectiveness profiles among antipsychotics may be a key point to optimize treatment in patients suffering a first episode of psychosis to impact on long-term outcome. The aim of this study is to compare the clinical effectiveness of olanzapine, risperidone, haloperidol, aripiprazole, ziprasidone, and quetiapine in the treatment of first episode of psychosis at 3-year follow-up. Method: From February 2001 to January 2011, 2 phases of a prospective, randomized, open-label study were undertaken. A total of 376 first-episode drug-naïve patients were randomly assigned to olanzapine (n=55), risperidone (n=63), haloperidol (n=56), aripiprazole (n=78), ziprasidone (n=62), or quetiapine (n=62) and followed up for 3 years. The primary effectiveness measure was all cause of treatment discontinuation. In addition, an analysis based on intention-to-treat principle was conducted in the analysis for clinical efficacy. Results: The overall dropout rate at 3 years reached 20.75%. Treatment discontinuation rates were significantly different among treatment groups (olanzapine=69.09, risperidone=71.43, aripiprazole=73.08%, ziprasidone=79.03%, haloperidol=89.28%, and quetiapine=95.53%) (x2=79.86; P=.000). Statistically significant differences in terms of lack of efficacy, adherence, and tolerability were observed among treatment groups along the 3-year follow-up, determining significant differences in time to all-cause discontinuation (log-rank=92.240; P=.000). Significant differences between treatments were found in the categories of sleepiness/sedation, increased sleep duration, akinesia, weight gain, ejaculatory dysfunction, extrapyramidal-symptoms, and amenorrhea. Conclusions: Olanzapine, risperidone, and aripiprazole presented advantages for the first-line treatment of first episode of psychosis in terms of effectiveness. Identifying different discontinuation patterns may contribute to optimize treatment selection after first episode of psychosis

Modified Serum ALP Values and Timing of Apparition of Knee Epiphyseal Ossification Centers in Preterm Infants with Cholestasis and Risk of Concomitant Metabolic Bone Disease of Prematurity

The usefulness of serum alkaline phosphatase (ALP) and phosphorous in screening and monitoring of metabolic bone disease of prematurity (MBDP) still has some limitations, especially in preterm infants with concomitant conditions such as cholestasis. We aimed to assess a modification of serum ALP (M-ALP) as a biomarker for MBDP in preterm infants, and the use of ultrasound monitoring for the apparition of knee ossification centers as marker of bone mineralization. Biochemical and clinical registers were taken from 94 preterm newborns 1 was demonstrated to be more specific (87.5%) in the diagnosis of MBDP than the cut-off value of serum ALP > 500 IU/L (62.5%). ALP/M-ALP > 1 showed 100% sensitivity and specificity for the diagnosis of MBDP, and a good correlation with specific bone ALP (B-ALP). Patients with the knee nucleus by post-menstrual week 37 had lower B-ALP compared to patients with no nucleus, and no patients with MBDP presented the nucleus by the 40th week. In the absence of reliable specific B-ALP, reinterpreting serum ALP values by M-ALP plus monitoring of knee ossification centers contribute to better management of MBDP in preterm infants with cholestasis

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

Long-Term Antipsychotic Effectiveness in First Episode of Psychosis: A 3-Year Follow-Up Randomized Clinical Trial Comparing Aripiprazole, Quetiapine, and Ziprasidone

BACKGROUND: Different effectiveness profiles among second-generation antipsychotics may be a key point to optimize treatment in patients suffering a first episode of psychosis to affect long-term outcome. The aim of this study was to compare the clinical effectiveness of aripiprazole, ziprasidone, and quetiapine in the treatment of first episode of psychosis at 3-year follow-up. METHOD: From October 2005 to January 2011, a prospective, randomized, open-label study was undertaken. Two hundred-two first-episode, drug-naïve patients were randomly assigned to aripiprazole (n=78), ziprasidone (n =62), or quetiapine (n=62) and followed-up for 3 years. The primary effectiveness measure was all cause of treatment discontinuation. In addition, an analysis based on the intention-to-treat principle was conducted in the analysis for clinical efficacy. RESULTS: The overall dropout rate at 3 years reached 19.3%. Treatment discontinuation rates were significantly different among treatment groups (aripiprazole=73.08%, ziprasidone=79.03%, and quetiapine=95.16%) (?2=11.680; P=.001). Statistically significant differences in terms of nonefficacy, nonadherence, and side effects were observed among treatment groups along the 3-year follow-up determining significant differences in time to all-cause discontinuation (log-rank=32.260; P=.001). Significant differences between treatments were found in the categories of sleepiness/sedation (?2=9.617; P=.008) and increased sleep duration (?2=6.192; P=.004). No significant differences were found in the profile of extrapyramidal symptoms. Patients on aripiprazole were more likely to be prescribed benzodiazepines. CONCLUSIONS: First-episode psychosis patients on quetiapine were more likely to discontinue treatment due to nonefficacy. Identifying different discontinuation patterns may contribute to optimize treatment selection after first episode of psychosis.This work was supported by Plan Nacional de Drogas Research (2005-Orden sco/3246/2004); SENY Fundacio (CI 2005–0308007); Fundacion Marques de Valdecilla (API07/011); and Gerencia Regional de Salud de Castilla y Leon (INT/M/04/17). The study was carried out at the Hospital Marques de Valdecilla, University of Cantabria, Santander, Spain. Unrestricted educational and research grants from AstraZeneca, Pfizer, Bristol-Myers Squibb, and Johnson & Johnson provided support for PAFIP activities. No pharmaceutical industry or institutional sponsors participated in the study design, data collection, analysis, or interpretation of the results

Early Intervention in Psychosis: From Clinical Intervention to Health System Implementation

Aim Early Intervention in Psychosis (EIP) is a well-established approach with the intention of early detection and treatment of psychotic disorders. Its clinical and economic benefits are well documented. This paper presents basic aspects of EIP services, discusses challenges to their implementation and presents ideas and strategies to overcome some of these obstacles. Methods This paper is a narrative review about the evidence supporting EIP, with examples of successful implementation of EIP and of cases where major obstacles still need to be overcome. Results Experience from successfully implemented EIP services into the mental healthcare system have generated evidence, concepts and specific strategies that might serve as guidance or inspiration in other countries or systems where EIP is less well developed or not developed at all. Previous experience has made clear that evidence of clinical benefits alone is not enough to promote implementation, as economic arguments and political and social pressure have shown to be important elements in efforts to achieve implementation. Conclusions Users’ narratives, close collaboration with community organisations and support from policy-makers and known people within the community championing EI services are just a few of the approaches that should be considered i

The effect of excess weight on circulating inflammatory cytokines in drug-naïve first-episode psychosis individuals

Background: Low-grade inflammation has been repeatedly associated with both excess weight and psychosis. However, no previous studies have addressed the direct effect of body mass index (BMI) on basal serum cytokines in individuals with first-episode psychosis (FEP). Objectives: The aim of this study is to analyze the effect of BMI on basal serum cytokine levels in FEP patients and control subjects, separating the total sample into two groups: normal-weight and overweight individuals. Methods: This is a prospective and open-label study. We selected 75 FEP patients and 75 healthy controls with similar characteristics to patients according to the following variables: sex, age, and cannabis and tobacco consumption. Both controls and patients were separated into two groups according to their BMI: subjects with a BMI under 25 were considered as normal weight and those with a BMI equal to or more than 25 were considered as overweight. Serum levels of 21 cytokines/chemokines were measured at baseline using the Human High Sensitivity T Cell Magnetic Bead Panel protocol from the Milliplex® Map Kit. We compared the basal serum levels of the 21 cytokines between control and patient groups according to their BMI. Results: In the normal-weight group, IL-8 was the only cytokine that was higher in patients than in the control group (p = 0.001), whereas in the overweight group, serum levels of two pro-inflammatory cytokines (IL-6, p = 0.000; IL-1?, p = 0.003), two chemokines (IL-8, p = 0.001; MIP-1?, p = 0.001), four Th-1 and Th-2 cytokines (IL-13, p = 0.009; IL-2, p = 0.001; IL-7, p = 0.001; IL-12p70, p = 0.010), and one Type-3 cytokine (IL-23, p = 0.010) were higher in patients than in controls. Conclusions: Most differences in the basal serum cytokine levels between patients and healthy volunteers were found in the overweight group. These findings suggest that excess weight can alter the homeostasis of the immune system and therefore may have an additive pro-inflammatory effect on the one produced by psychosis in the central nervous system.Funding: The present study was carried out at the Hospital Marqués de Valdecilla, University of Cantabria, Santander, Spain, under the following grant support from MINECO SAF2013-46292-R, Instituto de Salud Carlos III, and Fundación Marqués de Valdecilla. No pharmaceutical company has participated in the study concept and design, data collection, analysis and interpretation of the results, and drafting of the manuscript. We thank the Valdecilla Biobank for blood sampling handling and storage. We also wish to thank the participants and their families for enrolling in this study. The study, designed and directed by B C-F, conformed to international standards for research ethics and was approved by the local institutional review board

Mental impact of Covid-19 among Spanish healthcare workers. A large longitudinal survey

Aims: Longitudinal data on the mental health impact of the coronavirus disease 2019 (Covid-19) pandemic in healthcare workers is limited. We estimated prevalence, incidence and persistence of probable mental disorders in a cohort of Spanish healthcare workers (Covid-19 waves 1 and 2) -and identified associated risk factors. Methods: 8996 healthcare workers evaluated on 5 May-7 September 2020 (baseline) were invited to a second web-based survey (October-December 2020). Major depressive disorder (PHQ-8 ≥ 10), generalised anxiety disorder (GAD-7 ≥ 10), panic attacks, post-traumatic stress disorder (PCL-5 ≥ 7), and alcohol use disorder (CAGE-AID ≥ 2) were assessed. Distal (pre-pandemic) and proximal (pandemic) risk factors were included. We estimated the incidence of probable mental disorders (among those without disorders at baseline) and persistence (among those with disorders at baseline). Logistic regression of individual-level [odds ratios (OR)] and population-level (population attributable risk proportions) associations were estimated, adjusting by all distal risk factors, health care centre and time of baseline interview. Results: 4809 healthcare workers participated at four months follow-up (cooperation rate = 65.7%; mean = 120 days s.d. = 22 days from baseline assessment). Follow-up prevalence of any disorder was 41.5%, (v. 45.4% at baseline, p < 0.001); incidence, 19.7% (s.e. = 1.6) and persistence, 67.7% (s.e. = 2.3). Proximal factors showing significant bivariate-adjusted associations with incidence included: work-related factors [prioritising Covid-19 patients (OR = 1.62)], stress factors [personal health-related stress (OR = 1.61)], interpersonal stress (OR = 1.53) and financial factors [significant income loss (OR = 1.37)]. Risk factors associated with persistence were largely similar. Conclusions: Our study indicates that the prevalence of probable mental disorders among Spanish healthcare workers during the second wave of the Covid-19 pandemic was similarly high to that after the first wave. This was in good part due to the persistence of mental disorders detected at the baseline, but with a relevant incidence of about 1 in 5 of HCWs without mental disorders during the first wave of the Covid-19 pandemic. Health-related factors, work-related factors and interpersonal stress are important risks of persistence of mental disorders and of incidence of mental disorders. Adequately addressing these factors might have prevented a considerable amount of mental health impact of the pandemic among this vulnerable population. Addressing health-related stress, work-related factors and interpersonal stress might reduce the prevalence of these disorders substantially. Study registration number: NCT04556565.Instituto de Salud Carlos III/ Ministerio de Ciencia e Innovación/ FEDER (J. A., grant number COV20/00711); Project “PI17/00521”, funded by Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union, PERIS, Health Dpt, Generaliat de Catalunya (I. A., grant number SLT017/20/000009); ISCIII-FSE+, Miguel Servet (P. M., grant number CP21/00078); ISCIII-FSE, Sara Borrell (P. M., grant number CD18/00049), Generalitat de Catalunya (2017SGR452). Additional partial funding was received from the Gerencia Regional de Salud de Castilla y León (SACYL) (J. M. P. T., grant number GRS COVID 32/A/20).S