Measurement and reporting of the duration of untreated psychosis

Aim: The aim of this study was to investigate the demographic, illness and methodological factors associated with mean and median duration of untreated psychosis (DUP). Methods: A systematic review and meta‐analysis of the published studies of DUP and an examination of available DUP distributions. Results: DUP was longer in samples with a higher proportion of patients with schizophrenia and was shorter in samples that included affective psychosis. Sex, age, and the methods of measuring the onset and end‐point of DUP and the type of service in which the studies were performed did not contribute to the heterogeneity of the mean or median DUP values. Mean DUP is significantly prolonged by a small number of patients, and the median DUP is a poor indicator of the rate at which patients present. Conclusions: The DUP of patients with affective and non‐affective psychosis should be examined separately in order to make measures of DUP more meaningful and comparable, and DUP should be reported using more comprehensive measures. We suggest a method of reporting DUP based on the rate of presentation of first‐episode psychosis patients rather than the length of DUP.     

Early identification of non‐remission in first‐episode psychosis in a two‐year outcome study

Simonsen E, Friis S, Opjordsmoen S, Mortensen EL, Haahr U, Melle I, Joa I, Johannessen JO, Larsen TK, Røssberg JI, Rund BR, Vaglum P, McGlashan TH. Early identification of non‐remission in first‐episode psychosis in a two‐year outcome study. Objective: To identify predictors of non‐remission in first‐episode, non‐affective psychosis. Method: During 4 years, we recruited 301 patients consecutively. Information about first remission at 3 months was available for 299 and at 2 years for 293 cases. Symptomatic and social outcomes were assessed at 3 months, 1 and 2 years. Results: One hundred and twenty‐nine patients (43%) remained psychotic at 3 months and 48 patients (16.4%) remained psychotic over 2 years. When we compared premorbid and baseline data for the three groups, the non‐remitted (n = 48), remitted for <6 months (n = 38) and for more than 6 months (n = 207), duration of untreated psychosis (DUP) was the only variable that significantly differentiated the groups (median DUP: 25.5, 14.4 and 6.0 weeks, respectively). Three months univariate predictors of non‐remission were being single, longer DUP, core schizophrenia, and less excitative and more negative symptoms at baseline. Two‐year predictors were younger age, being single and male, deteriorating premorbid social functioning, longer DUP and core schizophrenia. In multivariate analyses DUP, negative and excitative symptoms predicted non‐remission at 3 months, but only DUP predicted at 2 years. Conclusion: Long DUP predicted both 3 month and 2‐year non‐remission rates in first‐episode psychosis.     

Duration of untreated psychosis and neuropsychological function in first episode psychosis

PURPOSE: We investigated whether duration of untreated psychosis (DUP) prior to first presentation was associated with cognitive function in first episode psychosis (FEP) subjects. We predicted that longer DUP would be associated with greater neurocognitive impairment. METHOD: 180 subjects with schizophrenia (and 93 subjects with Other Psychoses) performed a neurocognitive battery assessing IQ, verbal learning, working memory, visual learning and speed of processing. DUP was defined as the number of days between first onset of psychotic symptoms and first contact with psychiatric services. RESULTS: Longer DUP was associated with impaired performance in verbal IQ (p=0.04), verbal learning (p=0.02), and verbal working memory (p=0.04) in FEP subjects with schizophrenia. These associations remained significant for verbal IQ when scores were corrected for age, gender, educational level and ethnicity. CONCLUSIONS: Longer DUP is associated with poorer neurocognitive ability in schizophrenia subjects at time of first presentation. Since this was a cross-sectional study we can not tell whether longer DUP was a cause or a consequence of the poorer performance.     

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.     

Negative symptoms in first episode non-affective psychosis

OBJECTIVE: To determine the prevalence of negative symptoms and to examine secondary sources of influence on negative symptoms and the role of specific negative symptoms in delay associated with seeking treatment in first episode non-affective psychosis. METHOD: One hundred and ten patients who met Diagnostic Statistical Manual-IV (DSM-IV) criteria for a first episode of schizophrenia spectrum psychoses were rated for assessment of negative, positive, depressive and extrapyramidal symptoms, the premorbid adjustment scale and assessment of demographic and clinical characteristics including duration of untreated psychosis (DUP). RESULTS: Alogia/flat affect and avolition/anhedonia were strongly influenced by parkinsonian and depressive symptoms, respectively. A substantial proportion (26.8%) of patients showed at a least moderate level of negative symptoms not confounded by depression and Parkinsonism. DUP was related only to avolition/anhedonia while flat affect/alogia was related to male gender, diagnosis of schizophrenia, age of onset and the length of the prodrome. CONCLUSION: Negative symptoms that are independent of the influence of positive symptoms, depression and extra pyramidal symptoms (EPS) are present in a substantial proportion of first episode psychosis patients and delay in seeking treatment is associated mainly with avolition and anhedonia.     

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.     

Duration of untreated psychosis,ethnicity, educational level,and gender in a multiethnic South‐East Asian country: report from Malaysia schizophrenia registry

Introduction: Duration of untreated psychosis (DUP) determines the outcome of schizophrenia. Previously, there was no information about the DUP among patients in Malaysia with schizophrenia. The aim of the present study was to investigate the association between DUP and patients' demographic, social cultural background and clinical features. Method: This is a cross‐sectional study on patients who presented with first episode schizophrenia. Data from 74 primary care centers and hospitals between 1 January 2003 and 31 December 2007 were included in the analysis. All patients with first‐episode schizophrenia were enrolled in the study. Results: The mean DUP was 37.6 months. The indigenous community appeared to have the shortest DUP compared to the Malay, Chinese and Indian communities. Female, people with lower educational level, and comorbidity with medical illness during contact had longer DUP. Discussion: DUP in this multiethnicity country was found to be significantly short among the indigenous people, which may sugest that traditional values and strong family and community ties shorten the DUP. Educational level may need to be further investigated, because as upgrading the general educational level could lead to shorter DUP among the patients as well.     

Long-term effects of a community intervention for early identification of first-episode psychosis

Objective: To assess whether an Early Case Identification Program (ECIP) for first‐episode psychosis (FEP), which showed no significant short‐term effects, has a delayed impact on duration of untreated psychosis (DUP). Method: Using a historical control design, FEP patients were assessed on clinical variables over three consecutive phases, 2 years prior, 2 years during and 3 years after implementation of the ECIP. Additional analyses were conducted on non‐affective and schizophrenia spectrum psychoses cases only. Results: There was no overall significant difference in DUP across the three phases. For cases treated within the first year of illness a nonsignificant reduction in DUP to less than 2 months observed during the active phase was sustained post‐ECIP. Conclusion: In some jurisdictions community‐wide early case detection may fail to have an immediate or delayed effect on DUP, especially for cases who normally present for treatment with DUP >1 year.     

One year outcome in first episode psychosis: influence of DUP and other predictors

BACKGROUND: A number of studies have reported evidence of a relationship between longer duration of untreated psychosis (DUP) and poorer outcome at 1 year while others have failed to find such evidence. It is possible that several other predictors may confound this relationship and there may be different predictors for different dimensions of outcome. In the current study we examined relationship between DUP and several other predictors, and 1 year outcome on rate and level of remission as well as level of positive, negative, depressive and anxiety symptoms in a community cohort of first episode psychosis patients. METHOD: All potential cases of a first episode of non-affective psychosis were assessed and offered treatment in a comprehensive treatment program. Data were collected on all patients who completed 1 year of treatment on a number of predictor variables (DUP, length of the prodromal period, age of onset, gender, pre-morbid adjustment during childhood and adolescence, diagnosis) and outcome variables (level of remission, positive, negative, depression and anxiety symptoms based on ratings on SAPS, SANS, CDS and HAS, respectively). Data were analysed using an analysis of variance, bivariate correlations and hierarchical regression analysis. RESULTS: Of a total of 130 patients were offered treatment, 106 completed 1 year of treatment and complete data were available on 88 subjects, 80% of whom met criteria for schizophrenia spectrum psychosis. The rate and level of remission were significantly higher for patients with shorter DUP (<22 weeks). DUP was the only independent predictor of the level of remission as well as reality distortion at 1 year; for disorganization syndrome and negative symptoms it was the age of onset and level of premorbid adjustment in adolescence, respectively; while the level of anxiety was predicted by the length of the prodrome. Additional predictors increased the variance explained by each model. CONCLUSION: Our results confirmed the independent role of DUP in remission and positive symptom outcome at 1 year, thus providing support for the enthusiasm for early intervention. However, the model including DUP and premorbid adjustment in early adolescence explained a greater amount of variance in outcome on positive symptoms than DUP alone. On the other hand, outcome on negative symptoms, disorganization and anxiety are more likely to be influenced by longer term characteristics such as premorbid adjustment, earlier age of onset, gender and the length of the prodromal period, and therefore may not be as responsive to effects of early intervention.     

Cognitive deterioration and duration of untreated psychosis

Aim: To examine the relationship between cognitive deterioration and the duration of untreated psychosis (DUP) in a first‐episode psychosis sample. Method: We assessed a consecutive sample of first‐episode psychosis participants (N = 50) with measures of cognitive deterioration and DUP. Results: Using correlations and stepwise linear regressions, we found strong relationships between DUP and measures of cognitive deterioration. Conclusions: The length of DUP predicted cognitive deterioration. These results highlight a potential DUP grace period (>6 months) in which significant cognitive deterioration may be averted.     

Duration of untreated psychosis in a rural/suburban region of Japan

Aims: We examined the duration of untreated psychosis (DUP) and its social and clinical correlates in patients with schizophrenia in a rural/suburban region of Japan. Methods: We conducted a retrospective cohort study of patients with first‐episode psychosis from 11 hospitals in Kochi Prefecture. There were 108 patients who met the eligibility criteria, and data regarding their DUP and social/clinical variables were collected. Results: The median (mean) DUP of our cohort was 10.5 (34.6) months. Longer DUP was associated with younger age at onset, older age at first consultation, less educational attainment, insidious mode of onset and not being accompanied by another person at first consultation. After adjusting for confounding factors, age at onset, age at first consultation and mode of onset remained significantly and independently associated with DUP. In terms of treatment and response, longer DUP was associated with less antipsychotics prescribed upon first visit, and worse Clinical Global Impression Severity and Improvement scores after 1 year. Conclusion: The patients treated in a rural/suburban region of Japan had a long DUP, and shortening their DUP through promoting family involvement could improve their outcomes.     

Pathways to care and treatment delays in first and multi episode psychosis

BACKGROUND: In contrast to findings from the developed world where general practitioners and mental health professionals are central in first episode psychosis pathways, studies from Africa have found GPs to play a less prominent role with other help providers such as traditional healers being more important. METHODS: We compared pathways to care, treatment delays and gender differences in patients with first versus multi episode psychosis. RESULTS: Private sector GPs were first contacts in first episode patients in as many as 38% of patients and were significantly more likely to be the first contact (odds ratio = 4.5, 95% CI = 1.38-14.67) and final referring agent (odds ratio = 6.8, 95% CI = 1.56-25.12) in first episode patients. Female multi episode patients were significantly more likely to make first contact with primary care practitioners whereas male multi episode patients were more likely to first come into contact with the police (P = 0.003) and be admitted compulsorily (P = 0.009). Only 5.6% (n = 4) of patients contacted traditional healers at some point in their pathway to care. Treatment delays and DUP in first episode patients were longer and reached a median of 4.5 versus 2.5 months in multi episode patients. Treatment discontinuation of antipsychotics occurred in 82% of multi episode patients. Despite significantly longer overall treatment delays in first episode patients the distribution of treatment delays in multi episode patients followed a similar pattern to DUP in first episode patients with a subgroup having very long delays. CONCLUSIONS: Pathways to care in this treatment setting correspond more to findings from first world and newly industrialized countries. A subgroup of multi episode patients had very long periods of untreated illness. Limitations include small sample size and the retrospective nature of data collection.     

Duration of untreated psychosis and pathways to care in patients with first-episode psychosis in Iran

Aim: This is the first study on the duration of untreated psychosis and pathways to care among patients with first‐episode psychosis in Iran as a developing country. Methods: Ninety‐one patients with a first episode of non‐organic psychosis admitted to a university‐affiliated psychiatric hospital in Iran were assessed for duration of untreated psychosis (DUP), pathways to care and mode of onset. Results: Median DUP was 11 weeks (mean = 52.3 weeks). Following the onset of psychosis, most patients were first seen by a psychiatrist (n = 23, 25.3%), a traditional healer (n = 21, 23.1%) or a general practitioner (n = 16, 17.6%). Most referrals to the psychiatric hospital were made by the family (n = 30, 33.1%), or health professionals (n = 29, 31.9%). Acute onset and rural place of residence were associated with shorter DUP in multivariate analysis. Conclusions: Median DUP was not long in an inpatient sample with first‐episode psychosis, which may be due to the preponderance of affective and acute psychoses in this sample and some help‐seeking or service variables.     

Treatment delay and response rate in first episode psychosis

OBJECTIVE: There is no consistent evidence of long duration of untreated psychosis (DUP) predicting long time to response (TTR) in first psychosis. This study aims to investigate the predictors of DUP and TTR in a first episode patient population. METHOD: An epidemiologically representative sample of 157 non-affective first psychotic episode patients was interviewed and followed-up for at least half a year. RESULTS: The mean DUP was 46 weeks, the median 31 days. Long DUP was associated with being unemployed before treatment and male gender. Short DUP, having a job, and living with a partner before treatment predicted early response. CONCLUSION: Early intervention likely improves short-term treatment response in first episode psychosis. The best strategy to reduce DUP probably is to direct attention to the substantial number of patients who do not engage in regular treatment.     

首发精神分裂症未治时间对神经认知功能P300和P50预后的影响研究

目的DUP（duration of unmedicated psychosis）指精神疾病患者首次正式开始抗精神病治疗以前其精神病状态持续存在的时间。本研究探讨首发精神分裂症DUP对其神经认知功能的影响。方法收集从未服药首次发作精神分裂症患者70例和正常对照者54例，并对50例患者完成为期2个月随访。应用诺丁汉发病量表评估患者的DUP，应用DUP中位值将患者分为长DUP组和短DUP组。应用事件相关电位P300和感觉门控P50抑制评估神经认知功能。结果与对照者相比，分裂症患者P300波幅降低（P〈0．01），P300潜伏期延迟（P〈0．01），感觉门控P50抑制值异常升高（P〈0．01）。治疗前，长DUP组的P300潜伏期较短DUP组有延迟（352．1ms±36．7ms，336．0ms±29．0ms；F=4．2，P〈0．05）。治疗2个月后，仅短DUP组患者的P300波幅有明显改善（5．41xV±3．01．LV，7．31．LV±2．6uV，F=8．1，P〈0．01）。同时，两组患者的感觉门控P50抑制改善均不显著。结论DUP对首发精神分裂症患者神经认知功能预后有显著影响。如何预防长DUP的发生，值得关注。     

Duration of untreated psychosis and outcome of schizophrenia: delay in intensive psychosocial treatment versus delay in treatment with antipsychotic medication

Duration of untreated psychosis (DUP), defined as delay in treatment with antipsychotic medication, was found to be associated with an unfavorable course of schizophrenia. Delay in intensive psychosocial treatment (DIPT) may also be related to outcome. We examined the relationship of DUP and DIPT with several outcome domains 6 years after onset in a cohort of 88 consecutively admitted patients with early-onset schizophrenia and related disorders. Patients and their parents completed an inventory concerning DUP, DIPT, and various aspects of outcome. Psychotic relapse during the first year after hospitalization was assessed with a chart review. Both DUP and DIPT were found to be associated with negative symptoms at outcome; mode of onset was not. DUP was associated with mild psychotic relapse. DIPT was associated with months of rehospitalization. There was no relation between DUP or DIPT and other aspects of outcome. When we controlled for age at onset, gender, and duration of treated first psychotic episode, only DIPT was associated with negative symptoms at outcome. DIPT may be a more important predictor of negative symptoms at outcome than is delay in starting antipsychotic medication alone.     

Does duration of untreated psychosis bias study samples of first‐episode psychosis?

Objective: While findings are contradictory, many studies report that long Duration of Untreated Psychosis (DUP) correlates with poorer outcome in first episode psychosis. In an outcome study of first‐episode psychosis, we compared the patients who refused to participate in a follow‐along with those who consented to estimate the importance of this factor in sample recruitment bias. Our questions were: (i) What is the percentage of refusers? (ii) Are there systematic differences between refusers and consenters on DUP and/or other admission variables? (iii) What is the risk of refusal for different values of DUP? Method: In an unselected group of consecutively admitted patients we compared follow‐along refusers and consenters on the following admission variables: sex, age, diagnostic group, substance abuse, being in‐patient, coming from an early detection site and DUP. We conducted a logistic regression analysis with refusal as the outcome variable. Results: Ninety‐three of 397 patients (23%) were refusers. In univariate analyses the only significant difference was found for DUP. The median DUP for consenters was 10 weeks and for refusers 32 weeks. DUP remained significant when all independent variables were controlled for. Conclusion: DUP was significantly related to risk for refusal. For tests of the impact of DUP on outcome, this may introduce a type II error bias.     

Mental health laws that require dangerousness for involuntary admission may delay the initial treatment of schizophrenia

Introduction A long duration of untreated psychosis (DUP) is associated with a worse prognosis, an increased risk of suicide and may be linked to serious violence. Mental health laws that require patients to be dangerous to themselves or to others before they can receive involuntary psychiatric treatment may make it more difficult to treat patients in their first episode of psychosis. Methods The mean and median DUP reported in studies of schizophrenia related psychoses were examined. A comparison was made between the DUP reported from jurisdictions that had an obligatory dangerousness criterion (ODC) and those with other criteria for involuntary treatment. Results The average mean DUP in samples from jurisdictions with an ODC was 79.5 weeks, but was only 55.6 weeks in those jurisdictions that did not have an ODC (P < 0.007). Conclusions Mental health laws that require the patient to be assessed as dangerous before they can receive involuntary treatment are associated with significantly longer DUP. As reducing DUP is an intervention that can improve the prognosis of schizophrenia, this finding suggests that mental health laws should be amended to allow treatment on grounds other than dangerousness, at least in the crucial first episode of psychosis.