Clinical epidemiologic first-episode psychosis: 1-year outcome and predictors

OBJECTIVE: To describe 1-year outcome in a large clinical epidemiologic sample of first-episode psychosis and its predictors. METHOD: A total of 301 patients with first-episode psychosis from four healthcare sectors in Norway and Denmark receiving common assessments and standardized treatment were evaluated at baseline, at 3 months, and at 1 year. RESULTS: Substantial clinical and social improvements occurred within the first 3 months. At 1-year 66% were in remission, 11% in relapse, and 23% continuously psychotic. Female gender and better premorbid functioning were predictive of less severe negative symptoms. Shorter DUP was predictive for shorter time to remission, stable remission, less severe positive symptoms, and better social functioning. Female gender, better premorbid social functioning and more education also contributed to a better social functioning. CONCLUSION: This first-episode sample, being well treated, may be typical of the early course of schizophrenia in contemporary centers.     

Reducing the duration of untreated first-episode psychosis: effects on clinical presentation

CONTEXT: Most studies on first-episode psychosis show an association between a long duration of untreated psychosis (DUP) and poorer short-term outcome, but the mechanisms of this relationship are poorly understood. OBJECTIVE: To determine whether it is possible to reduce the DUP for first-episode patients in a defined health care area through the introduction of an early detection (ED) program, compared with parallel health care areas without an ED program (No-ED). SETTING AND PATIENTS: We included consecutive patients with a DSM-IV diagnosis of nonorganic, nonaffective psychosis coming to their first treatment in the study health care areas between January 1, 1997, and December 31, 2000. A total of 281 patients (76% of the total) gave informed consent. INTERVENTIONS: The ED and No-ED health care areas offered an equivalent assessment and treatment program for first-episode psychosis. The ED area also carried out an intensive ED program. RESULTS: The DUP was significantly shorter for the group of patients coming from the ED area, compared with patients from the No-ED areas (median, 5 weeks [range, 0-1196 weeks] vs 16 weeks [range, 0-966 weeks]). Clinical status measured by the Positive and Negative Syndrome Scale and the Global Assessment of Functioning Scale was significantly better for patients from the ED area at start of treatment and, with the exception of Positive and Negative Syndrome Scale positive subscale, at 3 months. Multiple linear regression analyses gave no indication that confounders were responsible for these differences. CONCLUSIONS: It is possible to reduce the DUP through an ED program. The reduction in DUP is associated with better clinical status at baseline that is maintained after 3 months.     

The key to reducing duration of untreated first psychosis: information campaigns

The TIPS early intervention program reduced the duration of untreated psychosis (DUP) in first-episode schizophrenia from 16 to 5 weeks in a health care sector using a combination of easy access detection teams (DTs) and a massive information campaign (IC) about the signs and symptoms of psychosis. This study reports what happens to DUP and presenting schizophrenia in the same health care sector when the IC is stopped. METHODS: Using an historical control design, we compare 2 cohorts of patients with first-episode Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition, non-affective psychosis at admission to treatment. The first cohort (N = 108) was recruited from January 1997 to December 2000, using an IC to raise awareness about recognizing psychosis to the public, the schools, and to general practitioners. The second cohort (N = 75) was recruited from January 2002 to June 2004 with no-IC. Easy access DTs were available to both cohorts. RESULTS: In the no-IC period, DUP increased back up to 15 weeks (median) and fewer patients came to clinical attention through the DTs. No-IC patients were diagnosed less frequently with schizophreniform disorder, more Positive and Negative Syndrome Scale positive and total symptoms, and poorer Global Assessment of Functioning (symptom) Scale scores. CONCLUSIONS: Intensive education campaigns toward the general public, the schools, and the primary health care services appear to be an important and necessary part of an early detection program. When such a campaign was stopped, there was a clear regressive change in help-seeking behavior with an increase in DUP and baseline symptoms.     

Early detection of first-episode psychosis: the effect on 1-year outcome

Early intervention is assumed to improve outcome in first-episode psychosis, but this has not been proven. OBJECTIVE: To study whether 1-year outcome will be better in a health care sector with early detection (ED) of psychosis compared with sectors with no early detection (no-ED). DESIGN: A quasi-experimental study with ED in 2 experimental sectors and no-ED in 2 control sectors. ED was achieved through low-threshold ED teams and information campaigns about psychosis for the public, schools, and primary health care providers. The ED and no-ED health care areas offered an equivalent assessment and treatment program during the first year. Two hundred and eighty-one patients were included; 88% were reassessed after 1 year. RESULTS: The ED-area patients (N = 141) had a median duration of untreated psychosis of 5 weeks at baseline compared with 16 weeks for patients in the no-ED area (N = 140). Positive and general symptoms, global assessment of functioning, quality of life, time to remission, and course of psychosis at 1 year after the start of treatment were not different between ED and no-ED groups. Outcome was significantly better for the ED area for negative symptoms. CONCLUSIONS: The ED, no-ED differences at baseline become attenuated by 1 year but not the difference in negative symptoms, suggesting secondary prevention in this domain of psychopathology. However, this possibility requires further testing by follow-up and replication.     

Determinants of help-seeking and system related components of delay in the treatment of first-episode psychosis

INTRODUCTION: Knowledge about factors that influence different components of duration of untreated psychosis (DUP) is important for designing interventions to reduce DUP. METHOD: We tested associations between help-seeking and referral components of DUP (DUP-H and DUP-R, respectively) and the following predictor variables: age, gender, ethnicity, living arrangement, pre-morbid adjustment, age at onset of psychosis, diagnosis, level of symptoms, type of first and total number of mental health contacts prior to and after the onset of psychosis in a sample of 98 first-episode psychosis patients (FEP). RESULTS: Longer DUP-HS was significantly associated with earlier age at onset, diagnosis of schizophrenia spectrum psychosis and poor pre-morbid adjustment during adolescence. Longer DUP-R was associated with earlier age at onset and first help-seeking contact having been made with a non-medical professional. CONCLUSIONS: Relatively non-malleable patient characteristics are likely to influence delay in help-seeking while more malleable systemic characteristics influence delay associated with referral for specialized treatment.     

Effects on referral patterns of reducing intensive informational campaigns about first-episode psychosis

Aim: The primary aim of this study was to assess referral patterns and duration of untreated psychosis (DUP) following the partial dismantling of intensive, information campaigns (IC) to help detect first‐episode, non‐affective psychosis via early detection teams in the TIPS study. Methods: We compared referral patterns of potential cases from the same geographical region (Rogaland County, Norway) referred to low‐threshold, rapid‐response detection teams at three timepoints: early‐IC period (1997–1998), late‐IC period (1999–2000) and the no‐IC period (2002–2003). Results: A significant increase occurred in the total number of phone calls, Positive and Negative Syndrome Scale (PANSS)‐interviews and referrals from families from the early‐to the late‐IC period. A comparison of the late‐IC period versus no‐IC period showed a significant decrease in the number of PANSS‐interviews administered, as well as fewer cases referred to the assessment teams. Additionally, a significant decline occurred in the number of referrals from general physicians, whereas the number of direct referrals to the hospital units increased. The DUP increased from a median of 5 to 14 weeks. Conclusion: External referrals to easy access detection teams occurred more frequently when IC were intensive, especially referrals from families and general practitioners. A shorter DUP was observed in the IC period, suggesting the importance of IC in augmenting the effectiveness of detection teams in identifying first‐episode psychosis early in the course of illness.     

Early intervention in first-episode psychosis

OBJECTIVE: Substantial delays in providing access to treatment in first-episode psychosis have been well documented. The present study examines the impact of strategies aimed at improving access and reducing delays. METHOD: A pilot community education campaign was conducted with the aim of reducing the duration of untreated psychosis (DUP) in a geographically defined intervention sector located in the northwestern region of Melbourne, Australia. Utilising a quasi-experimental design, a comparison sector with similar demographics was selected from another part of the north-western region. A mobile early detection team and the same treatment system served both sectors. RESULTS: While there was no significant difference between the mean DUP for intervention and comparison sectors, the distributional features of DUP between the two regions were significantly different. In the intervention sector, disproportionately more cases with very long DUP were detected. When a small number of outliers were removed, the mean and median DUP in the intervention sector was reduced. CONCLUSION: These findings highlight the complexity of treatment access and delay and suggest that efforts to reduce DUP may have two effects, not one. Firstly, a different sample of cases is treated through the detection of hidden "long DUP" cases that otherwise may have remained untreated. Secondly, the DUP for the remainder may indeed be reduced. More research with larger samples and more potent campaign strategies is clearly required. It may also be worth considering whether there is a safe and ethical way to undertake a RCT of early versus delayed antipsychotic treatment to perhaps settle the DUP debate once and for all.     

Duration of untreated psychosis may predict acute treatment response in first-episode schizophrenia

There is growing evidence for a relationship between the duration of untreated psychosis (DUP) and the prognosis in schizophrenia. The objective of this study is to evaluate whether DUP and premorbid level of social functioning are related to treatment response in acute treatment of first-episode schizophrenia. Seventy-nine first-episode schizophrenia patients were assessed with BPRS, SAPS, and SANS on admission and discharge during their first hospitalisation. Percentage of the difference between admission and discharge in total scores of all scales were taken as measures of absolute symptom reduction. The median DUP was 6 months (mean=8.6). DUP was correlated with reduction in BPRS and SAPS scores but not SANS scores. Patients with a short DUP (n=41) also showed a higher reduction in BPRS, and SAPS scores than those with a long DUP. Premorbid Adjustment Scale (PAS) scores were inversely correlated with age at onset and positively correlated with BPRS scores at admission. We did not find any relationship between PAS scores and response to treatment. Our findings suggest that DUP may be an important predictor of response in acute treatment of first-episode schizophrenia and thus, attempts for early diagnosis may also have a positive effect on acute treatment response.     

Reducing the duration of untreated first-episode psychosis -- effects on baseline social functioning and quality of life

OBJECTIVE: Long duration of untreated psychosis (DUP) is associated with poorer outcome. The TIPS study demonstrated that DUP can be reduced through early detection (ED). As quality of life (QoL) is associated with DUP it is expected that reduction of DUP leads to better QoL. METHOD: Consecutive first-episode patients with a DSM-IV diagnosis of non-organic, non-affective psychosis were included, 281 patients gave informed consent and 263 completed a full evaluation of QoL. RESULTS: There were no differences in subjective QoL between ED and No-ED groups attributable to reduction in DUP. There were significant bivariate differences in frequency of family and social contacts in favor of the ED group, but multivariate analyses indicated that these differences were based on differences in sample characteristics. CONCLUSION: Deterioration in QoL may precede overt symptom formation. Focus on functional loss in ED educational campaigns may identify risk subjects earlier in the course of the disorder.     

Duration of untreated psychosis and cognitive deterioration in first-episode schizophrenia

Cognitive impairment is an important clinical feature in many individuals with schizophrenia. Factors associated with cognitive deficit are not well established. Duration of untreated psychosis (DUP) has recently gained interest as a prognostic factor in schizophrenia. This study reports on the association between DUP and cognitive function. Subjects comprised 42 individuals (30 males, 12 females) who experienced a first-episode of DSM-III-R schizophrenia or schizophreniform disorder. Cognitive function was determined at clinical stabilization using the WAIS-R. An estimate of cognitive deterioration was based on the WAIS-R subtest profile. Longer DUP, male gender, higher premorbid IQ and younger age at admission independently predicted cognitive deterioration. Poorer performance on Digit Symbol and Comprehension subtests was associated with longer DUP. The findings suggest that untreated psychosis compromises some aspects of cognitive function. Studies investigating the association between DUP and outcome should control for potentially confounding variables. Early treatment of psychosis could help to reduce the prominent cognitive deficit in first-episode schizophrenia.     

Influence of duration of untreated psychosis on auditory P300 in drug-naive and first-episode schizophrenia

P300 amplitude reduction in schizophrenia is, according to previous studies, partially recovered by treatment with neuroleptics. However, whether this medication-induced P300 recovery is associated with duration of untreated psychosis (DUP) remains unreported; the present study is a preliminary examination of this question. Auditory P300 was recorded from 18 drug-naive and first-episode schizophrenia patients, among whom 10 were identified as short DUP, and eight as long DUP. Follow-up event-related potential tests were carried out after treatment with haloperidol or bromperidol for approximately 2 months. Recovery of P300 amplitude was replicated after neuroleptic medication was administered. A significant interaction was found between DUP and the medication effect in P300 amplitude over the left temporo-parietal area; a significant P300 recovery was seen in short DUP but not in long DUP. These results suggest that first-episode schizophrenia patients with long DUP might have severe impairments in the left temporal structures, supporting DUP as a key variable in future neurobiological studies of first-episode schizophrenia.     

Duration of Untreated Psychosis, Referral Route, and Age of Onset in an Early Intervention in Psychosis Service and a Local CAMHS

Background:  The aim of this study was to investigate associations between demographic and clinical variables and duration of untreated psychosis (DUP) in a sample of cases of psychosis across an adult early intervention in psychosis service and a child and adolescent community team.
Method:  Cross-sectional baseline data for cases of psychosis across the two teams on the caseload at a given time point were collected, including age of onset, gender, ethnicity, referral route, and DUP.
Results:  The median DUP across the entire sample was 91 days, while those patients with initial treatment for psychosis from the child and adolescent team had a median DUP of 69 days. Using multiple linear regression, there were two variables that showed a significant association with DUP: referral route ( p  < .001), and age of onset, with earlier age of onset associated with shorter DUP ( p  = .015).
Conclusion:  These findings are discussed in relation to possible explanatory factors, with particular focus on service-level variables and pathways to care. It is suggested that the involvement of child and adolescent teams is vital to the work of early intervention in psychosis services.     

Clinical and social determinants of a longer duration of untreated psychosis of schizophrenia in a Japanese population

Aim: To measure the duration of untreated psychosis (DUP) among patients with schizophrenia in a Japanese population and to investigate clinical and social determinants of the DUP. Methods: A multicentre, retrospective study at seven medical centres in three cities (Tokyo, Toyama and Kochi) was performed. In total, 150 consecutive patients (78 men) with neuroleptic-naïve first-episode schizophrenia were investigated; their DUP and demographic, clinical and social variables were obtained from their medical charts and analysed. Results: The intraclass correlation coefficient for the DUP was quite good (ICC = 0.849). The mean DUP of all the subjects attending the seven psychiatric services was 20.3 months, and the median DUP was 6.0 months. Fourteen patients (9.3%) had a DUP of more than 60 months, and 47 patients, or about one-third, had a DUP of more than 24 months. No significant differences in the mean DUPs were observed among the three cities. Patients who were employed or who were students had a significantly shorter DUP (14.3 months). The median DUP for those with an insidious onset of psychosis (n = 85) was 18.0 months, compared with a median of 2.0 months for those with a sudden and acute onset (n = 61). However, no other clinical or social variables examined in this study were associated with differences in the DUP. Conclusions: The DUP of patients with schizophrenia is relatively long in Japan. The provision and modification of psychiatric services for easy access and a system for the early recognition and detection of mental illness are needed.     

A case of prolonged duration of untreated psychosis: barriers to treatment and strategies to improve the outcome

Several factors may contribute to increase in duration of untreated psychosis (DUP). In most cases, early intervention, namely psychopharmacological or psychosocial intervention, is done after first-episode psychosis. It is important to know what factors can contribute to duration of untreated psychosis. During this phase, patients often display unspecific symptoms such as anxiety and depression, personality disorders, and abuse of alcohol or drugs. These symptoms could go unrecognized and, hence, cause a delay in seeking treatment. In addition, functional and social decline frequently occurs in the prodromal phase or in the early course of schizophrenia. The purpose of this paper is to highlight barriers that cause delay in treatment and to review early detection and specific treatment strategies that may help to improve outcomes leading to psychosocial recovery.     

Reducing the duration of untreated psychosis and changing help-seeking behaviour in Singapore

AIM: This study was conducted to examine the impact of early detection strategies of an early psychosis intervention programme on the duration of untreated psychosis (DUP) and the pattern of help-seeking behaviour. METHOD: Patients with first-episode psychosis were compared before and after the initiation of a programme of public education and networking with primary health care providers. These two groups were compared on the DUP and the change in the pattern of help-seeking. RESULTS: The DUP was significantly reduced from a median of 12 to median of 4 months (p=0.002, Mann-Whitney U-test). There was an increase in the proportion of self and family referrals, and a fall in the proportion of police referrals. CONCLUSION: Awareness campaigns which target multiple groups and use various modes of communication are effective in influencing the DUP and patterns of help-seeking.     

First-episode schizophrenia: do grandiosity, disorganization, and acute initial development reduce duration of untreated psychosis? An exploratory naturalistic case study

There is growing evidence for a relationship between the duration of untreated psychosis (DUP) and the prognosis. However, determinants of the DUP have been minimally explored, as is the detailed initial temporal unfolding of untreated psychosis. In this study, in-depth interviews with 19 first-episode DSM-IV schizophrenia patients and their relatives revealed detailed phenomenology of the initial prodrome and untreated psychosis. The findings suggest that a later prodrome onset (mean age in this sample, 20.5 years), a prodrome shorter than 2 years, acute initial psychosis development, the initial presence of grandiosity and/or disorganization, and a mild level of withdrawal all may reduce treatment delay. This set of characteristics might therefore represent built-in components of psychotic illnesses related to a shortened DUP, irrespective of early intervention efforts. In other words, the DUP could partly reflect these built-in aspects of psychosis. The rate of initial (untreated) psychosis development could contribute to broaden the prevailing mode of onset concept (presently defined as the duration of the initial prodrome) to comprise both the duration and content of the initial prodrome, as well as untreated psychosis, tentatively designated as the mode of initial psychosis development.     

Duration of untreated psychosis: are we ignoring the mode of initial development?. An extensive naturalistic case study of phenomenal continuity in first-episode schizophrenia

Duration of untreated psychosis (DUP) might affect the course and treatment outcome in schizophrenia significantly. Looking for potential determinants of DUP, researchers have mostly assessed the initial untreated psychosis in terms of plain duration, not developmental content. The present study provides empirical contributions to the discussion of phenomenal continuity throughout the entire untreated illness by pointing out continuous trajectories from prodrome to psychosis. In a series of 19 first-episode DSM-IV schizophrenia patients, we explore prodromal and untreated psychotic phenomena, and the data indicate that symptoms considered intrinsic to core psychosis phenomenology had attenuated antecedents in the prodromes, increasing continuously until treatment, whereas symptoms considered not intrinsic to core psychosis were characterized by fluctuations. Mode of initial psychosis development is proposed as a tentatively informative concept, comprising duration and content aspects of the initial prodrome and untreated psychosis.     

Determining the chronology and components of psychosis onset: The Nottingham Onset Schedule (NOS)

The Nottingham Onset Schedule (NOS) is a short, guided interview and rating schedule to measure onset in psychosis. Onset is defined as the time between the first reported/observed change in mental state/behaviour to the development of psychotic symptoms. Onset is conceptualised as comprising of (i) a prodrome of two parts: a period of 'unease' followed by 'non-diagnostic' symptoms; (ii) appearance of psychotic symptoms; and (iii) a build-up of diagnostic symptoms leading to a definite diagnosis. Twenty consecutive cases of first-episode psychosis were administered the NOS schedule to determine its psychometric properties including inter-rater and test-retest reliability. Its clinical and research potential as a reliable measure of duration of untreated psychosis (DUP) was assessed in a cohort of 99 cases of first-episode psychosis (56 schizophrenia, 43 affective psychoses). NOS identified all prodromal symptoms previously reported in other studies. There was high degree of inter-rater and test-retest reliability for all components of NOS. Duration of untreated psychosis was significantly longer (p<0.05) in schizophrenia (mean 179 days, S.D. 344; median 52 days) than in affective psychosis (mean 15 days, S.D. 116; median 12 days) but there were no gender differences between lengths of prodrome or treatment delays. The NOS provides a standardised and reliable way of recording early changes in psychosis and identifying relatively precise time points for measuring several durations in emerging psychosis. The scale is easy to use and is not time-consuming or labour intensive. Onset, as measured by NOS, is significantly longer in schizophrenic disorders than in affective psychosis. A small proportion of schizophrenia cases have very long DUP. Some cases with schizophrenia receive anti-psychotics in the prodromal phase, prior to the emergence of frank psychotic symptoms.     

Premorbid functioning versus duration of untreated psychosis in 1 year outcome in first-episode psychosis

OBJECTIVE: This study examines 1year outcome in patients having first-episode non-affective psychosis, with emphasis on Duration of Untreated Psychosis (DUP) and premorbid functioning, in order to clarify how these factors interact. METHOD: Forty-three consecutively admitted patients were all rated on the Positive and Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning Scale (GAF), both upon hospitalization and at 1year follow-up. In addition, premorbid functioning, DUP, duration of hospitalization, and social functioning were rated. RESULTS: Fifty-six per cent were in remission, 18% suffered multiple relapses and 26% were continuously psychotic at 1 year follow-up. Both poor premorbid functioning and long DUP are significantly correlated with more negative symptoms and poorer global functioning at follow-up. Long DUP is also significantly correlated with more positive symptoms. Even when we control for other factors, including premorbid functioning and gender, DUP is a strong predictor of outcome. To a limited degree premorbid functioning and DUP interact, but DUP has an independent influence on outcome. CONCLUSIONS: these findings strengthen the rationale for establishing health service programs for early detection and treatment of first-onset psychosis