Factors associated with improved outcomes in the first psychotic episode at a specialized outpatient clinic in northeastern Brazil.

OBJECTIVES: The present study aimed to evaluate data from patients admitted to the first-episode psychotic (FEP) outpatient clinic at the Hospital of Clinics of the Federal University of Pernambuco from July 2018 to July 2021, seeking to identify factors related to better clinical outcomes. METHODS: This study was conducted using a convenience sample, including all patients between 15 and 65 years of age who were admitted to the FEP outpatient clinic from July 2018 to July 2021. Descriptive statistical analysis was performed using mean and standard deviation or median and interquartile range for continuous quantitative variables, and absolute number/percentage for qualitative variables. Paired T-test, a parametric test, was used to compare PANSS scores upon admission and after 6 months. Spearman's correlation test was employed to assess the correlation between duration of untreated psychosis (DUP) and treatment response with other variables. RESULTS: The sample consisted of 85.3% male individuals, with 50% of patients aged between 19 and 30 years, and 82% residing in the metropolitan area of Recife. Seventy percent of patients responded to the treatment implemented by the outpatient clinic, and only 30% required psychiatric hospitalization within 6 months of follow-up. The majority of patients had a history of psychoactive substance use (82.4%); however, the use of these substances did not impact the prognosis within the analysed sample. The median DUP was 4 weeks, and a shorter DUP was associated with a lower probability of psychiatric hospitalization and a greater treatment response (reduction >50% in PANSS). CONCLUSION: A shorter DUP was associated with a lower likelihood of psychiatric hospitalization and a greater treatment response. Furthermore, the specialized early psychosis outpatient clinic itself appears to yield positive outcomes, as 70% of the treated patients exhibited a positive treatment response.

Impact of duration of untreated psychosis on remission in first-episode schizophrenia in Thailand: a cohort study

ABSTRACT Background: To scale up the services for first-episode schizophrenia in Thailand, it is essential to understand to what extent health care-seeking is delayed, and how much the delay affects the treatment outcome. Objectives: To investigate the duration of untreated psychosis (DUP) and its impact on remission in first-episode schizophrenia across the country. Methods: 276 outpatients with a first-episode schizophrenia were followed for 6 months and assessed whether they fulfilled the criteria for remission at the follow-up. The proportion of those achieving remission was compared by the DUP. The impact of DUP on remission was estimated in multivariate analyses. Results: At the follow-up, 83% (71/86) of patients who had met the criteria for symptomatic remission at the baseline achieved enduring remission, whereas 63% (119/190) of patients who had not met the criteria for symptomatic remission at baseline met it at the follow-up. The shorter the DUP, the higher the proportion of those who achieved symptomatic or enduring remission at the follow-up. The impact of DUP on symptomatic remission appeared to be significant after controlling for other factors influencing remission. Conclusion: Since the DUP would influence remission of patients with schizophrenia, early detection and intervention services should be provided in Thailand.

Duration of Untreated Psychosis in First-Episode Psychosis is not Associated With Common Genetic Variants for Major Psychiatric Conditions: Results From the Multi-Center EU-GEI Study.

Duration of untreated psychosis (DUP) is associated with clinical outcomes in people with a diagnosis of first-episode psychosis (FEP), but factors associated with length of DUP are still poorly understood. Aiming to obtain insights into the possible biological impact on DUP, we report genetic analyses of a large multi-center phenotypically well-defined sample encompassing individuals with a diagnosis of FEP recruited from 6 countries spanning 17 research sites, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. Genetic propensity was measured using polygenic scores for schizophrenia (SZ-PGS), bipolar disorder (BD-PGS), major depressive disorder (MDD-PGS), and intelligence (IQ-PGS), which were calculated based on the results from the most recent genome-wide association meta-analyses. Following imputation for missing data and log transformation of DUP to handle skewedness, the association between DUP and polygenic scores (PGS), adjusting for important confounders, was investigated with multivariable linear regression models. The sample comprised 619 individuals with a diagnosis of FEP disorders with a median age at first contact of 29.0 years (interquartile range [IQR] = 22.0-38.0). The median length of DUP in the sample was 10.1 weeks (IQR = 3.8-30.8). One SD increases in SZ-PGS, BD-PGS, MDD-PGS or IQ-PGS were not significantly associated with the length of DUP. Our results suggest that genetic variation does not contribute to the DUP in patients with a diagnosis of FEP disorders.

Similarities and Differences in Associations Between Duration of Untreated Psychosis (DUP) and Demographic, Premorbid, and Symptom Severity Measures in Two Samples of First-Episode Psychosis Patients from Mexico and the United States.

Early-psychosis researchers have documented that duration of untreated psychosis (DUP) is an important predictor of outcomes in first-episode psychosis. Very few cross-national studies have been conducted, and none have been carried out involving patients from both Mexico and the U.S. We collaborated to answer three questions: (1) Are DUP estimates similar in two very different settings and samples? (2) Are demographic variables, premorbid adjustment, and symptom severity similarly related to DUP in the two different settings? (3) Does the same set of variables account for a similar proportion of variance in DUP in the two settings? Data on sociodemographic characteristics, premorbid adjustment, symptom severity, and DUP were available for 145 Mexican and 247 U.S. first-episode psychosis patients. DUP was compared, and bivariate analyses and multiple linear regressions were carried out in each sample. DUP estimates were similar (medians of 35 weeks in Mexico and 38 weeks in the U.S.). In the Mexican sample, DUP was associated with gender, employment status, premorbid social adjustment, and positive symptom severity (explaining 18% of variance). In the U.S. sample, DUP was associated with age, employment status, premorbid social adjustment, and positive symptom severity (but in the opposite direction of that observed in the Mexican sample), accounting for 25% of variance. Additional cross-national collaborations examining key facets of early-course psychotic disorders, including DUP, will clarify the extent of generalizability of findings, strengthen partnerships for more internationally relevant studies, and support the global movement to help young people struggling with first-episode psychosis and their families.

Impact of duration of untreated psychosis in short-term response to treatment and outcome in antipsychotic naïve first-episode psychosis.

AIM: Duration of untreated psychosis (DUP) is one of the few potentially modifiable outcome predictors in psychosis. Previous studies have associated a longer DUP with a poor prognosis, but few of them were performed in countries with low and middle level of income. This study aimed to investigate the DUP in a Brazilian sample of antipsychotic-naïve first-episode psychosis (AN-FEP) patients and its association with clinical characteristics and treatment outcomes in a short-term follow-up. METHODS: One hundred forty-five AN-FEP patients between 16 and 40 years were enrolled and were reassessed 10 weeks after risperidone treatment. We investigated the association between DUP and symptom severity, functionality and response to treatment, using the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression-Severity Scale (CGI) and the Global Assessment of Functionality (GAF) scale. DUP was defined as the period between the onset of the first psychotic symptoms and the first effective antipsychotic treatment. For the analysis, we performed multivariate linear regressions. RESULTS: The DUP's median was 61 days. At baseline, we did not find any significant association between DUP and clinical characteristics. After treatment, the longer DUP predicted worse positive and negative symptom dimensions, worse total PANSS, GAF and CGI scores and poorer response to treatment. CONCLUSION: Our results showed that DUP is associated with worse outcomes after short treatment, but it does not modify the baseline clinical profile of the AN-FEP patients. Such results reinforce the need to develop early intervention strategies, reducing DUP.

Duration of untreated psychosis and acute remission of negative symptoms in a South American first-episode psychosis cohort.

AIM: To determine the association between duration of untreated psychosis (DUP) and symptoms remission in a hospitalized first-episode psychosis cohort. METHODS: Inpatients with a first-episode non-affective psychosis were recruited. Subjects were divided into two groups of long and short DUP using a 3-month cut-off point, and this was related to remission at 10 weeks of treatment. Multivariate analyses were performed. RESULTS: Fifty-five inpatients were included. There were no differences in remission rates of positive symptoms. Up to 76.5% of the patients with a short DUP (<3 months) achieved remission of negative symptoms versus 31.6% in the DUP ≥ 3 months group (P = 0.003). After controlling for relevant factors, patients with a shorter DUP were still three times more likely to achieve negative symptoms remission (HR: 3.04, 95% CI 1.2-7.5). CONCLUSIONS: DUP is a prognostic factor that should be considered at an early stage to identify a 'high risk' subgroup of persistent negative symptoms.

The efficacy of targeted health agents education to reduce the duration of untreated psychosis in a rural population.

The duration of untreated psychosis (DUP) is a key determinant in the severity of symptoms in patients with schizophrenia. DUP is a modifiable factor that if reduced can improve patient outcome and treatment response. We sought to decrease DUP in rural Argentina by instituting annual training of local health agents to better identify signs of mental illness and offer earlier intervention. DUP was estimated using Schedules of Clinical Assessment in Neuropsychiatry (SCAN). Ongoing training was correlated with a reduction in DUP. Reducing DUP through better screening can decrease the psychosocial burden of disease and improve the trajectory of psychosis.

Impacto de la duración de la psicosis no tratada (DPNT) en el curso y pronóstico de la esquizofrenia / Impact of Duration of Untreated Psychosis (DUP) in the course and outcome of schizophrenia

The duration of Untreated Psychosis (DUP), defined as the period of time between the onset of psychotic symptoms, such as hallucinations and delusions, and the first effective treatment, has been associated to prognosis of schizophrenia. It has been demonstrated that although psychotic symptoms are initially detected by relatives of patients with schizophrenia, they take a long time to seek specialized attention, which in turn leads to a delay in the diagnosis and treatment of the disorder. Schizophrenia has been considered by the World Health Organization as a public health problem and has been placed as the ninth cause of incapacity in the world. Thus, DUP represents part of this public health problem. In Mexico, the average DUP lasts 64 weeks, which is very similar to the average observed in other countries, where the mean DUP in psychotic patients varies between one and two years. One of the main reasons of a prolonged DUP is that patients and their families first assist with a general practitioner which, in many cases, does not perform an adequate diagnosis with the subsequent referral to a psychiatric facility, and the treatment given for the patient is based on sedative medication. This is also Mexico's case, where seeking help primarily involves religious groups, with very few referrals to psychiatric facilities and with inadequate treatment support, which delays care in specialized services. It has been established that early treatment is related to a better prognosis and outcome, while treatment delay has been related to a longer time to achieve symptom remission. These results support the hypothesis that the presence of psychotic symptoms for a long period of time may predispose to biological damage, which may in turn lead to predominant negative symptoms and severe cognitive deficits after the first psychotic episode. Also, some studies have found that a longer DUP is related to a more insidious illness onset, frequent relapses and psychiatric hospitalizations during the course of the disorder, with a poor response to antipsychotic medication. Through the use of neuroimaging, several studies have found the relation between DUP and brain morphology in patients with schizophrenia. Studies using Magnetic Resonance Imaging (MRI) have reported that patients with longer DUP show a significant reduction in the gray matter of the temporal planum, in the left middle, inferior temporal, left occipital and left fusiform cortices, with an increase of grey matter in the left basal ganglia, and a volume reduction of the caudate nucleus. These results may be related to the clinical course of the disorder in terms of a higher symptom severity and poor treatment response. In regard to psychosocial variables related to DUP, it has been observed that men have a longer DUP when compared to women and patients that are single and unemployed also have a longer DUP. Consequently, it has been found that there is a relationship between DUP and premorbid adjustment in patients with schizophrenia. Premorbid adjustment is defined as the psychosocial functioning in the educational, occupational, social and interpersonal relations areas before the evidence of positive characteristic symptomatology, where symptoms are not secondary to an organic cause and cover a period of six months before the first psychiatric hospitalization or contact with a psychiatric facility. In addition, it has been found that a prolonged DUP is related to a poor premorbid adjustment, especially during late adolescence and adulthood. This association may suggest the presence of prodromic symptoms secondary to the physiopathological process of psychosis. Consequently, if a patient shows some of the initial symptoms of the disorder, including psychosocial impairment, his/her abilities to be aware of the symptoms may be limited to seek for medical care, which may in turn increase DUP. Furthermore, some authors have reported that some variables related to the patient's environment are related with DUP. The main variable pointed out is: the previous experience with mental disorders and psychiatric facilities. Patients whose families had previous experience of a mentally ill relative, report a shorter DUP when compared to families with no previous history of an ill relative. Also, it has been analised that patients with an adequate social network have a shorter DUP compared to those patients whose social network is inadequate or limited. Based on these results, some authors have proposed two phenotypes for psychotic disorders: the first one characterized by males, poor premorbid adjustment, long DUP, insidious onset of the disorder and a stable pattern of negative symptoms. The second phenotype was one characterized by the following variables: females, good premorbid adjustment, a shorter DUP, acute illness onset and absence of a stable pattern of negative symptoms. This definition may be useful to determine the course of the disorder in patients with schizophrenia and may be able to predict the clinical outcome. Thus, DUP can be used as an indicator of prognosis in patients with schizophrenia and its evaluation should be promoted. Although these two phenotypes are very useful, caution should be warranted in their use to avoid generalization. By and large, the studies related to the clinical impact of DUP emphasized the need to reduce DUP through early detection programs, including psychoeducation. We believe that this approach will be useful to identify individuals at an early development of a psychotic illness so that interventions can begin before symptoms have reached a level of significant impairment for the patient and warranting referrals by the family, school or health providers. Based on the studies reviewed above, we can conclude that DUP has a definitive impact on the prognosis of patients with schizophrenia and that future studies should be performed including it not only as a predictor of clinical outcome, but also as an specific clinical target for mental health research. Increasing the knowledge about the relationship between DUP and clinical course of schizophrenia is crucial to create and promote early detection and intervention programs such as the ones that have started all over the world, where the main objective is to identify young people who are at risk of developing psychotic disorders, specially schizophrenia.

La duración de la psicosis no tratada (DPNT), definida como el período de tiempo entre la aparición de los síntomas psicóticos y el inicio de un tratamiento adecuado, está asociada al pronóstico de la esquizofrenia, enfermedad que ha sido considerada por la Organización Mundial de la Salud, como un problema de salud pública. El atraso en la búsqueda de tratamiento especializado conlleva a un retraso en el diagnóstico y tratamiento adecuados de la enfermedad. En México, el promedio de la DPNT es de 64 semanas, siendo éste similar al reportado en otros países, donde la media varía entre uno y dos años. Se ha comprobado que el retraso en el tratamiento adecuado del padecimiento está relacionado con un pobre pronóstico, lo cual apoya la hipótesis de que la presencia de síntomas psicóticos durante un largo período de tiempo puede predisponer a un daño biológico, generando así un predominio de síntomas negativos y mayores déficit cognitivos después del primer episodio psicótico. Además, se ha encontrado que una DPNT larga se relaciona con un inicio insidioso de la enfermedad, mayor número de recaídas y rehospitalizaciones psiquiátricas durante el curso de la enfermedad, además de una pobre respuesta al tratamiento farmacológico con antipsicóticos. En cuanto a las variables demográficas y psicosociales que se asocian con una DPNT prolongada encontramos: al sexo masculino, el no tener pareja u ocupación laboral. Asimismo, se ha reportado que los pacientes que presentan un mayor deterioro en su funcionamiento premórbido, son aquellos que muestran una mayor DPNT. Esta asociación sugiere que los pacientes con esquizofrenia pueden presentar síntomas prodrómicos mucho tiempo antes de que su funcionamiento se vea totalmente afectado por el proceso fisiopatológico de la psicosis. Asimismo, se han reportado variables relacionadas con el entorno del paciente asociadas a la DPNT. Entre ellas, destacan la experiencia previa con trastornos mentales y las redes sociales. Se ha observado que los pacientes de familias que han tenido una experiencia previa con otro familiar diagnosticado con alguna enfermedad mental, muestran una menor DPNT en contraste con aquellos cuyas familias no han tenido experiencias previas de enfermedades mentales. De igual forma, se ha informado que pacientes con una adecuada red social tienen una menor DPNT, comparados con aquellos cuya red social es limitada. A partir de estos hallazgos se han propuesto dos fenotipos para los trastornos psicóticos cuya definición puede ser útil para determinar el curso clínico de la enfermedad en pacientes con esquizofrenia. En este sentido, la DPNT se puede utilizar como un indicador para el pronóstico de pacientes con esquizofrenia, por lo que se sugiere promover su evaluación. Los estudios que se han llevado a cabo sobre el impacto clínico de la DPNT enfatizan la necesidad de reducirla mediante programas de detección temprana. Estos programas serían útiles para identificar personas en etapas iniciales de un trastorno psicótico y se podría realizar una intervención profesional antes de que los síntomas alcancen un nivel de deterioro significativo para el paciente. Con base en lo anterior, se puede concluir que la DPNT tiene un fuerte impacto sobre el pronóstico de los pacientes con esquizofrenia y que en el futuro se deben realizar estudios que la incluyan no sólo como un factor pronóstico, sino como un objetivo clínico específico de la investigación en salud mental, ya que la información que se genere puede ser la base para la creación y promoción de programas de detección e intervención tempranas.