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: a proposition regarding treatment definition

Aim: Duration of untreated psychosis (DUP) refers to the time elapsing between psychosis onset and treatment initiation. Despite a certain degree of consensus regarding the definition of psychosis onset, the definition of treatment commencement varies greatly between studies and DUP may be underestimated due to lack of agreement. In the present study, three sets of criteria to define the end of the untreated period were applied in a first‐episode psychosis cohort to assess the impact of the choice of definition on DUP estimation. Methods: The DUP of 117 patients admitted in the Treatment and Early Intervention in Psychosis Program Psychosis in Lausanne was measured using the following sets of criteria to define treatment onset: (i) initiation of antipsychotic medication; (ii) entry into a specialized programme; and (iii) entry into a specialized programme and adequate medication with a good compliance. Results: DUP varied greatly according to definitions, the most restrictive criteria leading to the longest DUP (median DUP1 = 2.2 months, DUP2 = 7.4 months and DUP3 = 13.6 months). A percentage of 19.7 of the patients who did not meet these restrictive criteria had poorer premorbid functioning and were more likely to use cannabis. Longer DUP3 was associated with poorer premorbid functioning and with younger age at onset of psychosis. Conclusion: These results underline the need for a unique and standardized definition of the end of DUP. We suggest that the most restrictive definition of treatment should be used when using the DUP concept in future research.     

Premorbid adjustment, symptom development and quality of life in first episode psychosis: a systematic review and critical reappraisal

Objective: To systematically review the relationship of premorbid adjustment to symptomatology in first episode psychosis (FEP), taking into account the influence of duration of untreated psychosis (DUP). Method: Electronic databases were searched to identify relevant studies. Results: A variety of approaches to the reporting of premorbid adjustment were identified. There was no significant association between premorbid adjustment and DUP, supporting the proposition that they are independent constructs. The effect of premorbid adjustment upon positive symptomatology was negligible. Premorbid adjustment had a modest effect upon negative symptoms and quality of life, increasing over duration of follow‐up. Conclusion: Premorbid adjustment remains a valid construct in the study of FEP. Both premorbid adjustment and DUP confer independent effects on aspects of symptomatology in FEP. Results for premorbid adjustment are similar to previous findings in more chronic samples. The potential for conceptualizing premorbid functioning by developmental, academic/social and typological approaches is currently underexploited.     

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.     

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.     

Does a detection team shorten duration of untreated psychosis?

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.     

Early premorbid adjustment as a moderator of the impact of duration of untreated psychosis

OBJECTIVES: Shorter duration of untreated psychosis (DUP) is often correlated with a poorer response to treatment. In this paper we test the hypothesis that the importance of DUP is moderated by early premorbid adjustment. METHOD: Three year prospective data were collected for 154 first episode patients. DUP, premorbid adjustment and symptoms were assessed at time of presentation for treatment and symptoms were reassessed after three years of treatment. RESULTS: DUP was correlated with level of symptoms at three years only for patients with better premorbid adjustment in childhood and early adolescence. CONCLUSIONS: These results suggest that DUP may have more of an impact on treatment response for those with a less pernicious, more reversible form of illness.     

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.     

Predictors of acute treatment response in patients with a first episode of non-affective psychosis: sociodemographics, premorbid and clinical variables

Approximately 60% of patients with a first episode of psychosis will significantly reduce the severity of their positive symptomatology with antipsychotic drugs. The aim of this study was to investigate predictors of response to antipsychotic treatment during the first episode of non-affective psychosis. 172 patients (107 male) with a diagnosis of schizophreniform, schizophrenia, schizoaffective, brief reactive psychosis, schizotypal personality disorder or psychosis non-otherwise specified entered the study. Sociodemographic, premorbid and clinical data at baseline were evaluated. Unpaired t-test for continuous and chi2 for categorical data, respectively, were used to compare responders and non-responders selected variables. Multivariate logistic regression was used to establish a prediction model. 57.6% of study subjects (99 of 172) responded to antipsychotic treatment. The following variables were significantly associated with less likelihood of response: 1.--lower severity of general psychopathology, positive symptoms and disorganized symptoms at baseline; 2.--earlier age of onset; 3.--diagnosis of schizophrenia; 4.--longer DUP; 5.--poorer premorbid adjustment during adolescence, and 6.--hospitalization. Multivariate logistic regression demonstrated that differences between responders and non-responders were largely accounted for by BPRS total score, age of onset, premorbid adjustment at early adolescence, and diagnosis. Patients with an early age of onset of schizophrenia, a poor premorbid adolescent functioning, and with a lower severity of psychopathology at intake seem to have a decrease likelihood of responding to antipsychotic treatment. Helping clinicians to identify non-responders is meant as a first step to optimise therapeutic effort to benefit individuals in this vulnerable group.     

Understanding Components of Duration of Untreated Psychosis and Relevance for Early Intervention Services in the Canadian Context: Comprendre les Composantes de la Durée de la Psychose Non Traitée et la Pertinence de Services D’intervention Précoce Dans le Contexte Canadien

Background:Clinical, functional, and cost-effectiveness outcomes from early intervention services (EIS) for psychosis are significantly associated with the duration of untreated psychosis (DUP) for the patients they serve. However, most EIS patients continue to report long DUP, while a reduction of DUP may improve outcomes. An understanding of different components of DUP and the factors associated with them may assist in targeting interventions toward specific sources of DUP.Objectives:To examine the components of DUP and their respective determinants in order to inform strategies for reducing delay in treatment in the context of an EIS.Methods:Help-seeking (DUP-H), Referral (DUP-R), and Administrative (DUP-A) components of DUP, pathways to care, and patient characteristics were assessed in first episode psychosis (N = 532) patients entering an EIS that focuses on systemic interventions to promote rapid access. Determinants of each component were identified in the present sample using multivariate analyses.Results:DUP-H (mean 25.64 ± 59.00) was longer than DUP-R (mean = 14.95 ± 45.67) and DUP-A (mean 1.48 ± 2.55). Multivariate analyses showed that DUP-H is modestly influenced by patient characteristics (diagnosis and premorbid adjustment; R ² = 0.12) and DUP-R by a combination of personal characteristics (age of onset and education) and systemic factors (first health services contact and final source of referral; R ² = 0.21). Comorbid substance abuse and referral from hospital emergency services have a modest influence on DUP-A (R ² = 0.08). Patients with health care contact prior to onset of psychosis had a shorter DUP-H and DUP-R than those whose first contact was after psychosis onset (F(1, 498) = 4.85, P < 0.03 and F(1, 492) = 3.34, P < 0.07).Conclusions:Although much of the variance in DUP is unexplained, especially for help-seeking component, the systemic portion of DUP may be partially determined by relatively malleable factors. Interventions directed at altering pathways to care and promote rapid access may be important targets for reducing DUP. Simplifying administrative procedures may further assist in reducing DUP.     

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.     

EEG abnormalities and 3-year outcome in first episode psychosis

Objective: This study assesses the relationship of EEG to several aspects of 3 year symptomatic and functional outcome in first episode psychosis. Method: A total of 117 patients with first episode psychosis had their baseline EEG classified by modified Mayo Clinic criteria as normal, essentially normal or dysrhythmia. Socio‐demographic variables, duration of illness and of untreated psychosis and premorbid adjustment were also recorded. Positive and negative symptoms of psychoses, depression, anxiety and global functioning were rated on entry and after 3 years of treatment. Results: Patients with a dysrhythmic EEG at entry into treatment showed significantly greater persistence in both positive and negative symptoms of psychoses as well as anxiety and depression over 3 years. These findings were independent of duration of untreated illness or premorbid adjustment. Conclusion: An abnormal baseline EEG in patients with first episode psychosis is associated with a poorer symptomatic outcome at 3‐year follow‐up.     

Neural correlates of movement generation in the ‘at‐risk mental state’

Broome MR, Matthiasson P, Fusar‐Poli P, Woolley JB, Johns LC, Tabraham P, Bramon E, Valmaggia L, Williams SCR, Brammer MJ, Chitnis X, McGuire PK. Neural correlates of movement generation in the ‘at‐risk mental state’. Objective: People with ‘prodromal’ symptoms have a very high risk of developing psychosis. We examined the neurocognitive basis of this vulnerability by using functional MRI to study subjects with an at‐risk mental state (ARMS) while they performed a random movement generation task. Method: Cross‐sectional comparison of individuals with an ARMS (n = 17), patients with first episode schizophreniform psychosis (n = 10) and healthy volunteers (n = 15). Subjects were studied using functional MRI while they performed a random movement generation paradigm. Results: During random movement generation, the ARMS group showed less activation in the left inferior parietal cortex than controls, but greater activation than in the first episode group. Conclusion: The ARMS is associated with abnormalities of regional brain function that are qualitatively similar to those in patients who have recently presented with psychosis but less severe.     

Gender and duration of untreated psychosis: a systematic review and meta-analysis

Aim: Duration of untreated psychosis (DUP) can influence the prognosis of schizophrenia. Previous studies have suggested that gender may influence the length of DUP. This study reports the result of the first systematic literature review and meta‐analysis on the role of gender in influencing DUP in first‐episode psychosis. Method: Systematic literature search in PubMed/Medline and Ovid/PsychINFO. Twenty‐seven studies presenting data on 4721 patients diagnosed with psychosis at their first episode (2834 males and 1887 females) were included in the analysis. Results: Samples had a higher proportion of males: odds ratio = 2.5 (95% confidence interval: 1.8–3.3). Mean age at first contact was 25.4 for males and 27.5 for females. Patients from non‐Western countries were older at first contact than patients from Western countries. Average DUP in schizophrenia was 64 weeks and did not differ between genders but was shorter in Western compared with non‐Western countries. Conclusion: Earlier age at first contact and larger incidence in males support the existence of specific gender differences in first‐episode psychosis; however, these are not associated with DUP length.     

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.     

Family strengths: a potential determinant of the duration of untreated psychosis among hospitalized African-American first-episode patients

Aim: Evidence suggests that treatment delay, represented by the duration of untreated illness (DUI) and the duration of untreated psychosis (DUP), may be a potentially powerful determinant of the early course of primary psychotic disorders. Yet, research on the predictors of treatment delay has only just begun. To date, there are virtually no empirical data on the relationship between family functioning and treatment delay in the context of first‐episode psychosis. In this study, it was hypothesized that family strengths would be inversely correlated with DUI and DUP; and families of patients with a short DUI/DUP would have greater family strengths than those of patients with a long DUI/DUP. Methods: Family strengths (including pride and accord dimensions), DUI and DUP were assessed in 34 African Americans hospitalized for first‐episode psychosis and their respective 34 family members most involved in initiating care. Results: The total score of the Family Strengths scale and the accord subscale score were significantly inversely correlated with both DUI and DUP, although the correlation between the pride subscale score and DUI/DUP was not as strong and failed to reach statistical significance. Similarly, the family members of patients with a short DUI/DUP had higher family strength scores than those of patients with a long DUI/DUP. Conclusions: Given the dearth of research on the functioning of families beginning to initiate care for individuals with first‐episode psychosis, it is imperative to further clarify the role family characteristics may play in understanding treatment delay (DUI/DUP) and in the development of preventive interventions to facilitate early intervention for at‐risk populations.     

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.     

Factors associated with functional psychosocial status in first-episode psychosis

Aim: This study aimed to determine which of demographic/premorbid, psychiatric or neuropsychological variables are most closely associated with functional status around the time of diagnosis of first‐episode psychosis. This was with a view to determining factors that should be the focus of intervention in these early stages of illness. Methods: The Western Sydney First Episode Psychosis Project collected data on young persons (aged 13–25) with newly diagnosed psychosis (n = 92). Psychosocial functional status was measured using the Role Functioning Scale (RFS). Multiple regression analyses were carried out to identify predictors of RFS score from a wide range of predictor variables. Results: Psychiatric variables accounted for the most variance in RFS score. Positive and Negative Syndrome Scale (PANSS) Negative subscale and Young Mania Rating Scale score were found to be significant individual predictors, with variables from the other domains failing to contribute to the overall model. In separate models, demographic/premorbid and neuropsychological factors weakly related to functional status. Conclusions: Psychiatric factors were the main influence on psychosocial functioning in first‐episode psychosis at baseline. Evidence suggests the relationships between symptoms, cognition and demographics with function might change over time, depending on the stage of illness being examined.     

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.