Showing papers by "Merete Nordentoft published in 2008"

Five-year follow-up of a randomized multicenter trial of intensive early intervention vs standard treatment for patients with a first episode of psychotic illness: the OPUS trial.

Abstract: Context Intensive early treatment for first-episode psychosis has been shown to be effective. It is unknown if the positive effects are sustained for 5 years. Objective To determine the long-term effects of an intensive early-intervention program (OPUS) for first-episode psychotic patients. Design Single-blinded, randomized, controlled clinical trial of 2 years of an intensive early-intervention program vs standard treatment. Follow-up periods were 2 and 5 years. Setting Copenhagen Hospital Corporation and Psychiatric Hospital, Aarhus, Denmark. Patients A total of 547 patients with a first episode of psychosis. Of these, 369 patients were participating in a 2-year follow-up, and 301 were participating in a 5-year follow-up. A total of 547 patients were followed for 5 years. Interventions Two years of an intensive early-intervention program vs standard treatment. The intensive early-intervention treatment consisted of assertive community treatment, family involvement, and social skills training. Standard treatment offered contact with a community mental health center. Main Outcome Measures Psychotic and negative symptoms were recorded. Secondary outcome measures were use of services and social functioning. Results Analysis was based on the principles of intention-to-treat. Assessment was blinded for previous treatment allocation. At the 5-year follow-up, the effect of treatment seen after 2 years (psychotic dimension odds ratio [OR], −0.32; 95% confidence interval [CI], − 0.58 to − 0.06; P = .02; negative dimension OR, − 0.45; 95% CI, − 0.67 to − 0.22; P = .001) had equalized between the treatment groups. A significantly smaller percentage of patients from the experimental group were living in supported housing (4% vs 10%, respectively; OR, 2.3; 95% CI, 1.1-4.8; P = .02) and were hospitalized fewer days (mean, 149 vs 193 days; mean difference, 44 days; 95% CI, 0.15-88.12; P = .05) during the 5-year period. Conclusions The intensive early-intervention program improved clinical outcome after 2 years, but the effects were not sustainable up to 5 years later. Secondary outcome measures showed differences in the proportion of patients living in supported housing and days in hospital at the 5-year follow-up in favor of the intensive early-intervention program.

Prenatal stressors of human life affect fetal brain development

Abstract: UMMARY In a population-based study, 3021 women in a central Copenhagen district received a questionnaire on environmental and psychological factors during mid-gestation. Of these, 70 women were selected consecutively on the basis of moderate to severe stressful life-events (DSM-111-R categories 3 to 5), in combination with an inadequate social network. They were compared with 50 non-stressed women with an intact social network. Stress and smoking significantly affected birthweight and head circumference. When birthweight was corrected, stress remained a significant determinant of small head circumference, indicating a specific effect on brain development. Stress also led to a sub-optimal Prechtl neonatal neurological score. These findings suggest the existence of a fetal stress syndrome with adverse effects on fetal development, including deficient brain development. RESUME Les stress prenataux de la vie journaliere affectent le developpemeni cerebral foetal Au cours d'une etude de population, 3021 femmes d' un district central de Copenhague recurent un questionnaire concemam les facteurs environnementaux et psychologiques a miterme. Dans ce groupe, 70 femmes furent choisies sequentiellement sur la base d'evenements provoquant un stress modere a severe (categories 3 a 5 du DSM-111-R) associe a un environnement social inadapte. Elles furent comparees a 50 femmes non stressees et avec environnement social intact. Le stress et le tabac affectaient significativement le poids de naissance et le tour de tete. Apres correction sur le poids de naissance, le stress demeurait un facteur significatif de faible tour de tete, indiquant un effet specifiqiie sur le developpemeni cerebral. Le stress produit egalement un score neurologique neonatal dc Prechtl sous-optimal. Ces donnees suggerent I'existence d'un syndrome foetal de stress avec des effets nocifs sur le developpemeni foetal, incluant un developpemeni cerebral deficient. ZUSAMMENFASSUNG .Pranatale Stressfaktoren des taglichen Lebens beeinflussen die fetale Hirnentwicklung In eincr die gesamte Bevolkerung eines Kopenhagener Wohnbezirkes umfassenden Studie erhielten 3021 Frauen cinen Fragebogen uber Umwelteinflusse und psychologische Faktoren wahrend des zweiten Sehwangerschaftstrimesters. Von diesen wurden 70 Frauen mit masigen bis schweren Stressercignissen (DSM-III-R Kategorie 3–5) in Kombinaiion mit unzureichender sozialer Absicherung ausgcwahlt. Diese wurden mit einer Gruppe von 50 nicht gestressten und sozial abgesicherten Frauen verglichen. Stress und Rauchen beeinflusten signifikant Geburtsgewicht und Kopfumfang. Nach Korrektur fur das Geburtsgewicht blieb Stress ein signifikanter Faktor fur den Kopfumfang, d.h. Stress hat eine spezifische Wirkung auf die Hirnentwicklung. Stress war auch die Ursache fur ein nicht optimales Ergebnis beim neurologischen Neugeborenentest nach Prechtl. Diese Befunde weisen auf die Fxistcnz eines fetalen Stress-Syndroms hin, das die fetale Entwicklung und insbesondcre die Hirnentwicklung ungunstig beeinflust. RESUMEN Los faaores estresantes de la vida humana afectan el desarrollo del cerebro humano En un estudio de poblacion de base, 3021 mujeres de un distrito central de Copenhague contestaron un cucstionario sobre faclores ambientales y psicologicos durante la gestacion, en la mitad de la misma. De ellas, 70 mujeres fueron seleccionadas consccutivamente sobre la base de haber sufrido acontecimicntos estressantcs (DSM-III-R categorias 3 a 5) en combinacion con un ambiente social inadecuado. Se compararon con 50 mujeres no estressadas con un ambiente social intacto. El estress y el fumar afectaban significativamente el peso del recicn nacido y su perimetria craneal. Cuando el peso de nacimiento era corregido, el estress era el linico factor determinante de una craneoperimetria pequefla, indicando un cfecto especifico sobre el desarrollo del cerebro. El estress tambien daba lugar a un puntaje neurologico neonatal de Prechtl suboptimo. Estos hallazgos sugieren la existencia de un sindrome de estress fetal. Con efectos adversos sobre el desarrollo fetal incluyendo un desarrollo cerebral deficiente.

The association between pre-morbid adjustment, duration of untreated psychosis and outcome in first-episode psychosis.

Abstract: Background The association between the duration of untreated psychosis (DUP) and outcome of schizophrenia may be confounded by other factors such as poor pre-morbid adjustment. The aim of the present study was to examine the independent contributions of DUP and of pre-morbid adjustment to the clinical and social outcomes of schizophrenia. Method A longitudinal, prospective, 2-year follow-up study of 423 patients with first-episode schizophrenia-spectrum psychosis was conducted. Patients were comprehensively assessed at entry, 1-year and 2-year follow-up. At entry, DUP was measured by IRAOS (an instrument for the assessment of onset and early course of schizophrenia) and pre-morbid adjustment was measured by the Pre-morbid Adjustment Scale (PAS) as 'pre-morbid social adaptation' and 'pre-morbid school adaptation'. Outcome measures included the Scale for the Assessment of Positive Symptoms (SAPS), the Scale for the Assessment of Negative Symptoms (SANS), the Social Network Schedule and social information. Multiple linear regression models were used for data analysis. Results The median DUP was 48 weeks, which is long compared to other studies. Longer DUP was independently associated with more psychotic symptoms at entry, 1-year and 2-year follow-up. Poorer pre-morbid social adaptation was independently associated with more negative symptoms and smaller social network at entry and 1-year follow-up. Poorer pre-morbid school adaptation was independently associated with poor vocational outcome at 1-year and 2-year follow-up. Conclusions Longer DUP is associated with poorer 2-year outcome of psychosis in schizophrenia-spectrum disorders, when pre-morbid functioning and other prognostic factors are controlled for. Impaired pre-morbid development is independently associated with more negative symptoms and poorer social outcome.

Predictors of remission and recovery in a first-episode schizophrenia spectrum disorder sample: 2-year follow-up of the OPUS trial.

Abstract: Objective:To examine the frequency and predictors of good outcome for patients with first-episode schizophrenia spectrum disorder (SSD).Method:We conducted a 2-year follow-up of a cohort of patient...

Impaired childhood development and suicidal behaviour in a cohort of Danish men born in 1953

Abstract: Background: Few studies have examined the correlation between social circumstances during childhood and adult suicide behaviour in a prospective design. How indicators of impaired childhood development affect the risk of suicide behaviour before the age of 50 years are analysed in this study. Method: 9359 Men born in Copenhagen, Denmark, in 1953, who had completed conscription medical examination at approximately 18 years of age and for whom birth certificates had been traced were followed from 1972 to 2003 in Danish health registers regarding suicide or suicide attempts. At the age of 12 years 6856 of these cohort members had completed a cognitive performance test. Results: During follow-up, 92 (1.0%) and 228 (2.4%) of the men, respectively, committed suicide or had one or more suicide attempt. Low body mass index (BMI), low cognitive test score, and mental disorder at the age of 18 years were associated with an increased risk of suicide. After adjustment, mental disorder remained significantly associated with suicide risk (hazard ratio 2.49, 95% CI 1.03 to 6.02), whereas the estimates for cognitive function (HR 0.77, 95% CI 0.59 to 1.01) and BMI (HR 0.81, 95% CI 0.64 to 1.02) were attenuated. In the crude analyses suicide attempt was associated with all indicators, but after adjustment mental disorder (HR 2.64 (95% CI 1.55 to 4.49), no more than a basic school education (HR 2.28, 95% CI 1. 30 to 4.00), BMI (HR 0.87, 95% CI 0.75 to 1.00) and cognitive test score at the age of 18 years (HR 0.85, 95% CI 0.72 to 1.01) were associated with the risk of suicide attempt. Conclusion: This study suggests that low BMI, low cognitive function, and mental disorder in early adulthood are markers of an increased risk of suicide among men born in Denmark in 1953.

Gender differences in suicidal intent and choice of method among suicide attempters.

Abstract: The objective was to examine gender differences in choice of method and suicidal intent among persons referred to a suicide prevention center. A total of 351 consecutive patients who had attempted suicide were interviewed using the European Parasuicide Study Interview Schedule I (EPSIS I) while participating in a 2-week inpatient treatment program. They were invited to a 1-year follow-up interview, and followed in the National Patient Register. Compared to women, men who had attempted suicide were older, had better self-esteem, fewer depressive symptoms, and higher total suicidal intention scores, but they were not more likely to use violent methods. Neither use of violent method nor dangerousness of the attempt was associated with suicidal intention. Although men had higher suicide intent scores than women, there were no significant gender differences in the number of repeat suicide attempts during a 1-year follow-up period. Suicidal intent was not related to dangerousness of suicide method.

Coercion in patients who at their first contact with the psychiatric services system were diagnosed within the schizophrenia- spectrum in Denmark. A register study

Abstract: The level of use of coercive measures in patients diagnosed with a schizophrenia-spectrum disorder at their first contact with the psychiatric services system in Denmark is not known. The aim of the study was to investigate the level of use of coercive measures during first year of contact in this group of patients. Using the longitudinal national registers, the use of coercive measures for each individual was calculated in a 1-year period from 1 January 1999 to 31 December 2001, for patients in Denmark who at their first contact with the psychiatric services system were diagnosed within the schizophrenia-spectrum (F2 in ICD 10); 2222 patients were identified. The mean age was 30.7 years and 63.6% were males; 554 patients (24.9%) experienced use of coercive measures. A total of 222 patients (10.0%) were admitted involuntarily, 308 (13.9%) were detained. Seventy-two patients (3.2%) were treated involuntarily with anti-psychotic medication and 158 (7.1%) with sedative medication. A total of 241 patients (10...

Design paper: The CapOpus trial: A randomized, parallel-group, observer-blinded clinical trial of specialized addiction treatment versus treatment as usual for young patients with cannabis abuse and psychosis

Abstract: A number of studies indicate a link between cannabis-use and psychosis as well as more severe psychosis in those with existing psychotic disorders. There is currently insufficient evidence to decide the optimal way to treat cannabis abuse among patients with psychosis. The major objective for the CapOpus trial is to evaluate the additional effect on cannabis abuse of a specialized addiction treatment program adding group treatment and motivational interviewing to treatment as usual. The trial is designed as a randomized, parallel-group, observer-blinded clinical trial. Patients are primarily recruited through early-psychosis detection teams, community mental health centers, and assertive community treatment teams. Patients are randomized to one of two treatment arms, both lasting six months: 1) specialized addiction treatment plus treatment as usual or 2) treatment as usual. The specialized addiction treatment is manualized and consists of both individual and group-based motivational interviewing and cognitive behavioral therapy, and incorporates both the family and the case manager of the patient. The primary outcome measure will be changes in amount of cannabis consumption over time. Other outcome measures will be psychosis symptoms, cognitive functioning, quality of life, social functioning, and cost-benefit analyses. ClinicalTrials.gov NCT00484302.

Does a detection team shorten duration of untreated psychosis

Abstract: Introduction: Duration of untreated psychosis (DUP) is shown to be associated with poor outcome in many domains. It has been shown that it is possible to shorten DUP when combining a detection team and an information campaign. The aim of this study was to evaluate whether DUP was shortened during the first 3 years after establishing detection teams without a concomitant information campaign. Methods: All patients included in the OPUS trial were examined with the Instrument for Retrospective Assessment of Onset of Psychosis to determine DUP. A total of 552 patients with first episode psychotic disorder (n = 470) or schizotypal disorder (n = 82) were included in the study. The 3-year inclusion period was divided into six consecutive periods of 6 months each. Results: The median DUP was 52 weeks. DUP was not significantly reduced during the 3-year inclusion period, but a larger proportion of patients with symptoms below the threshold for frank psychosis were included compared with the beginning of the trial. The proportion referred from primary care remained small (8–10%) and unchanged during the inclusion period. Discussion: The availability of a detection team increased the referral of patients with schizotypal disorder, but the DUP among psychotic patients remained almost unaltered throughout the period. It seems that an information campaign and possibilities for direct access and self-referral are necessary in order to shorten DUP.

The challenge of suicidal behaviour in early psychosis.

Abstract: Much attention has been paid to the risk of suicide in schizophrenia. As Miles in a review estimated that the risk of suicide was 10%, this figure had been repeated many times in reviews and comments. However, most likely this figure is too high, and in a recent review, Palmer et al. identified all firstepisode studies and estimated the lifetime risk to be 5.6%. Similarly, in their estimation of lifetime risk of suicide in various disorders, Inskip et al. estimated the lifetime risk in schizophrenia to be 4%. Even though the estimates of lifetime risk in schizophrenia may not reach 10%, the suicide risk is much higher among these patients compared with the general population. Comprehensive analyses of suicides have shown that people with severe mental illness form a particularly high-risk group. Analyses of data extracted from Danish registers also reveal that the greatest risk of suicide occurred just after admission to hospital or just after discharge, and that for patients with disorders in the schizophrenia spectrum, the first year of treatment was associated with approximately 60% increased risk of suicide compared with the whole group of patients who had been admitted because of these disorders. The absolute risk of suicide was highest among the elderly patients, but the excess risk compared with the general population was highest in the young age groups. Though both Danish studies and a recent Finnish study have shown decreasing suicide rates among patients with schizophrenia during the last decades, the risk of suicide in patients with disorders in the schizophrenia spectrum is still approximately 20-fold higher than in the general population. Suicidal behaviour and suicidal ideation is much more common than suicides. A total of 28% of patients included in the OPUS trial had had at least one suicide attempt before first contact with psychiatric services and the same percentage with suicide attempt before first contact was found in the LEO trial. In the TIPS project, Melle et al. found lower figures; 16% of first-episode psychotic patients from the areas without early detection strategies attempted suicide before first contact with psychiatric services, and 5% in the early detection areas had done so previously in their lifetime. Few randomized controlled trials have been conducted with the aim of reducing suicidal behaviour in schizophrenia, and there is hardly any evidence supporting the effectiveness of interventions on suicidal behaviour and mortality. This problem is partly due to the fact that studies would need very high numbers of participants to show a significant, clinically relevant difference between two or more treatment groups. Hawton et al. conducted a review of risk factors for suicide in schizophrenia and found that hopelessness and depressive symptoms, suicidal thinking and suicidal attempts, agitation and motor restlessness, fear of mental disintegration, poor adherence to treatment and recent loss were the strongest risk factors, as was drug (but not alcohol) abuse. A review of risk factors for suicide attempt in schizophrenia identified past or recent suicidal ideation, previous deliberate self-harm, past depressive episode, drug abuse or dependence, and higher mean number of psychiatric admissions as predictors. Depression, previous suicidal plans and suicidal thoughts were also the strongest predictors of suicide attempt in the OPUS trial. These results clearly indicate that to prevent suicidal behaviour among first-episode psychotic patients it is necessary to focus on the group of patients with depressive symptoms and suicidal behaviour and ideation. In this issue of Early Intervention in Psychiatry, Harris et al. publish the results of a retrospective non-randomized comparison of first-episode psychotic patients who have received early intervention services and those who have not. The design is naturalistic, and the paper is based on longitudinal data. In such design, it is necessary to control for possible differences in suicide risk in the two comparison cohorts, as selection bias might be responsible for differences in suicide rates. However, after careful control for potential confounders, the results seem to indicate a protective effect of early intervention services, although still ongoing, which is in line with the findings of Bertelsen et al. Although the results should be interpreted cautiously, the results of the analyses carried out by Harris et al. seem to indicate that suicide risk could be Early Intervention in Psychiatry 2008; 2: 1–2 doi:10.1111/j.1751-7893.2007.00052.x

Phases of psychosis

Abstract: Psychosis develops through several phases. Longitudinal high-risk studies and birth cohort studies have shown that persons who later develop schizophrenia have lower cognitive and social function levels, slower neuromotor development and more emotional problems. Almost 20 percent achieve full recovery after a psychotic episode, approximately 25 percent undergo remission, but do not meet the criteria for full recovery, 15 percent need institutional care, and another approx. 40 percent remain chronically psychotic.

[Psycho-social interventions in early psychoses within the schizophrenia spectrum].

Abstract: The possibilities for intervention in the early phases of schizophrenia and schizophrenia-like psychosis were reviewed. Long duration of untreated psychosis is related to persistent psychotic symptoms. Early detection programmes can reduce the duration of untreated psychosis and thereby probably improve outcome. There is ample evidence that intensive specialised assertive intervention during the early phase of psychotic symptoms is effective in improving several outcomes. Family intervention reduces risk of remission and improve compliance with antipsychotic medication.