Antipsychotic medication and remission of psychotic symptoms 10years after a first-episode psychosis.

BACKGROUND: Several national guidelines recommend continuous use of antipsychotic medication after a psychotic episode in order to minimize the risk of relapse. However some studies have identified a subgroup of patients who obtain remission of psychotic symptoms while not being on antipsychotic medication for a period of time. This study investigated the long-term outcome and characteristics of patients in remission of psychotic symptoms with no use of antipsychotic medication at the 10-year follow-up. METHODS: The study was a cohort study including 496 patients diagnosed with schizophrenia spectrum disorders (ICD 10: F20 and F22-29). Patients were included in the Danish OPUS Trial and followed up 10years after inclusion, where patient data was collected on socio-demographic factors, psychopathology, level of functioning and medication. FINDINGS: 61% of the patients from the original cohort attended the 10-year follow up and 30% of these had remission of psychotic symptoms at the time of the 10-year follow up with no current use of antipsychotic medication. This outcome was associated with female gender, high GAF-F score, participation in the labour market and absence of substance abuse. CONCLUSION: Our results describe a subgroup of patients who obtained remission while not being on antipsychotic medication at the 10-year follow-up. The finding calls for further investigation on a more individualized approach to long-term treatment with antipsychotic medication.

Predictors and longitudinal course of cognitive functioning in schizophrenia spectrum disorders, 10years after baseline: The OPUS study.

BACKGROUND: Identifying baseline predictors of the long-term course of cognitive functioning in schizophrenia spectrum disorders is important because of associations between cognitive functioning (CF) and functional outcome. Determining whether CF remains stable or change during the course of illness is another matter of interest. METHODS: Participants from The Danish OPUS Trial, aged 18-45years, with a baseline ICD-10 schizophrenia spectrum diagnosis, were assessed on psychopathology, social and vocational functioning at baseline, and cognitive functioning 5 (N=298) and 10years (N=322) after baseline. Uni- and multi-variable regression analyses of potential baseline predictors of 10-year CF were performed. Also, changes in CF and symptomatology between 5 and 10years of follow-up were assessed. FINDINGS: Baseline predictors of impaired CF after 10years included male gender, unemployment, poor premorbid achievement and later age of onset. Having finished high school and receiving early intervention treatment was associated with better CF. Age, growing up with both parents, number of family and friends, primary caregivers education, premorbid social function, negative symptoms, GAF (symptoms, function) and substance abuse, were associated with CF in univariable analyses. Non-participants generally suffered from more severe dysfunction. Longitudinally, amelioration in negative symptoms was associated with improved speed of processing and executive functions. Symptom scores generally improved with time, while scores for all cognitive tests remained stable. CONCLUSION: The current study identifies several robust associations between baseline characteristics and 10-year cognitive outcome. Several other variables were univariably associated with 10-year cognitive outcome. Also, we found evidence for stability of CF over time.

Trajectories of suicidal ideation in patients with first-episode psychosis: secondary analysis of data from the OPUS trial.

BACKGROUND: Heterogeneity in suicidal ideation over time in patients with first-episode psychosis is expected, but prototypical trajectories of this have not yet been established. We aimed to identify trajectories of suicidal ideation over a 3-year period and to examine how these trajectories relate to subsequent suicidality. METHODS: We used longitudinal data from the prospective 10-year follow-up OPUS trial of young Danish patients with first-episode psychosis. Participants were recruited between January, 1998, and December, 2000, from all inpatient and outpatient mental health services in Copenhagen and Aarhus County, were aged between 18 and 45 years, and had a diagnosis in the schizophrenia spectrum. Randomisation was done by a computer-generated randomisation list, stratified in alternating blocks for five centres. In Aarhus, a secretary drew lots when the researcher phoned her. Patients were randomly assigned to a treatment group (modified assertive community treatment) or a control group (standard treatment at community mental health centres) and assessed at treatment initiation, and after 1, 2, 5, and 10 years. We included all patients' data on suicidal ideation from the first three assessments in a latent growth mixture modelling analysis to empirically identify trajectories of suicidal ideation. Multivariable logistic regression analyses were applied to estimate associations between trajectories and subsequent suicidality. This trial is registered with ClinicalTrials.gov, number NCT00157313. FINDINGS: Three trajectories for suicidal ideation were identified in 521 patients. 317 of 521 members (61%) of the largest trajectory, low-decreasing, consisted of patients who initially reported suicidal ideation once-to-a-few-times in the past year followed by a decrease in suicidal ideation. 172 of 521 (33%) members of the frequent-stable trajectory reported suicidal ideation sometimes-to-frequently at the first assessment and remained stable over time. Finally, 32 of 521 (6%) members of the frequent-increasing trajectory reported frequent suicidal ideation initially followed by worsening. Compared with the low-decreasing class, the risk of persistent suicidal ideation was higher for patients in the frequent-stable and frequent-increasing classes at 5 years (Odds ratio=4·5, 95% CI 2·50-8·02 and 4·7, 1·55-14·24 respectively) and at 10 years (4·2, 2·42-7·13 and 3·2, 1·20-8·70 respectively). Also the risk of suicide attempt at 5 years was higher for patients in the frequent-stable (2·8, 1·07-7·43) and frequent-increasing classes (6·6, 1·69-25·54) compared with the low-decreasing class. There was no difference in suicide rate at 5 or 10 years between trajectories. INTERPRETATION: Because up to 40% of patients experienced frequent suicidal ideations that persisted or increased during the first years of treatment, our findings warrant special focus on suicidal issues as an integral part of treatment along with treatment to target psychotic symptoms. FUNDING: The Danish Council for Independent Research (Medical Sciences), Trygfonden, The Mental Health Services of the Capital Region of Denmark, The Danish Ministry of Health, The Danish Ministry of Social Affairs, the Psychiatry and Social Service Department in Central Denmark Region, and The Lundbeck Foundation.

Long-term trajectories of positive and negative symptoms in first episode psychosis: A 10year follow-up study in the OPUS cohort.

OBJECTIVE: Knowledge about course of illness can help clinicians to develop effective interventions and improve treatment outcomes. The goal of this study was to construct positive and negative symptom trajectories based on structured clinical assessments collected over 10years within a cohort of people with first episode psychosis. METHOD: A cohort of 496 people with first episode psychosis (ICD-10, F20-28) originally recruited for the OPUS study (1998-2000) and treated in community psychiatric services were rated on clinical symptoms at 5 different occasions across ten years. Psychopathology was assessed using the Scales for Assessment of Positive and Negative Symptoms. Symptom trajectories were constructed using Latent Class Analysis. RESULTS: Five distinct trajectories were identified for positive symptoms (response - 47%, delayed response - 12%, relapse - 15%, non-response - 13% and episodic response - 13%). Four distinct trajectories were identified for negative symptoms (response - 28%, delayed response - 19%, relapse - 26% and non-response - 27%). Multivariable regression analysis of baseline characteristics identified that longer duration of untreated psychosis (OR 1.27-1.47, p<0.05) and substance abuse (OR 3.47-5.90, p<0.01) were associated with poorer positive symptom trajectories (higher levels of psychotic symptoms) while poor social functioning (OR 1.34-5.55, p<0.05), disorganized symptoms (OR 2.01-2.38, p<0.05) and schizophrenia diagnosis (OR 5.70-8.86, p<0.05) were associated with poorer negative symptom trajectories (higher levels of negative symptoms). A proportion of people displayed significant changes in symptoms several years after diagnosis. CONCLUSIONS: Trajectories of illness for positive and negative symptoms were heterogeneous among people with first episode psychosis. Positive symptoms showed a general pattern of reduction and stabilization over time while negative symptoms typically showed less variation over the ten years. Results have implications for the focus, timing and length of interventions in first episode psychosis.

Ten-year follow-up of the OPUS specialized early intervention trial for patients with a first episode of psychosis.

INTRODUCTION: Specialized early intervention programs such as The Danish OPUS treatment are efficient in treating patients with a first episode of psychosis (FEP) at least after 2 and 5 years. Few studies have examined long-term outcomes of these interventions. AIM: To examine the effect of 2 years of OPUS vs treatment as usual (TAU) within an FEP cohort, 10 years after inclusion into the OPUS trial. METHODS: From 1998 to 2000, participants were randomized to OPUS or TAU. Ten years later, we conducted comprehensive interviews and performed register-based follow-up on all participants in national Danish registers. We analyzed participants according to the intention-to-treat principle. RESULTS: Of the 547 participants included in the study, 347 (63.4%) took part in this follow-up. While there was evidence of a differential 10-year course in the development of negative symptoms, psychiatric bed days, and possibly psychotic symptoms in favor of OPUS treatment, differences were driven by effects at earlier follow-ups and had diminished over time. Statistically significant differences in the course of use of supported housing were present even after 8-10 years. There were no differences between OPUS and TAU regarding income, work-related outcomes, or marital status. CONCLUSION: Most of the positive short-term effects of the OPUS intervention had diminished or vanished at this long-term follow-up. We observed a clear tendency that OPUS treatment leads to fewer days in supported housing. There is a need for further studies investigating if extending the intervention will improve outcomes more markedly at long-term follow-ups.

Predictors of recovery in first episode psychosis: the OPUS cohort at 10 year follow-up.

BACKGROUND: Recovery, the optimal goal in treatment, is the attainment of both symptomatic and functional remission over a sustained period of time. Identification of factors that promote recovery can help develop interventions that facilitate good outcomes for people with first episode psychosis. AIM: To examine long-term outcomes within a cohort of people with first episode psychosis in relation to symptom remission, functioning and recovery, 10 years after diagnosis. METHOD: The study had a prospective design. Participants from the OPUS trial (1998-2000) (n=496) completed a series of interviews and questionnaires to measure current levels of psychopathology and social/vocational functioning, ten years after diagnosis. Predictors of recovery were identified using socio-demographic and clinical characteristics collected at baseline. RESULTS: A total of 304 participants were interviewed, giving a follow-up rate of 61%. A total of 42 people (14%) met the criteria for symptomatic and psychosocial recovery at 10 years. A multivariable binary logistic regression analysis indicated that baseline predictors accounted for 22% of the variance of full recovery. Lower severity of negative symptoms at baseline (Odds Ratio (OR) 0.53, 95% confidence interval CI 0.36-0.78, p<0.001) and earlier age of diagnosis (OR 0.92, 95% CI 0.86-0.99, p<0.05) predicted better rates of recovery at 10 years. CONCLUSION: Results of this study indicated that negative symptoms could play a central role in the process of recovery from schizophrenia. A challenge for clinicians and researchers is to understand the mechanisms behind negative symptoms and develop interventions that can prevent or ameliorate these symptoms in order to promote recovery.