Duration of untreated psychosis may predict acute treatment response in first-episode schizophrenia
Introduction
In the past two decades, greater attention has been focused on early course of schizophrenia and duration of untreated psychosis (DUP). Studies of first-episode schizophrenia have noted that the time between the onset of positive symptoms and first effective treatment is often very long (Larsen et al., 2001, Maurer & Hafner, 1995, McGlashan, 1999). The average DUP across studies lies between 9 weeks (median) and 2 years (Hafner et al., 1994, Ring et al., 1991). Variation in the results may be related to the differences in patients' and their families' help-seeking behaviour, availability of psychiatric treatment, tolerance of disrupted behaviour by the society, and assesment methods used. It is generally accepted that clinicians can define DUP with good reliability, but that dating first noticeable symptoms proved to be more difficult (Beiser et al., 1993).
It is still unclear what determines DUP in schizophrenia. Some of its predictors are illness related and others are related with the attitudes of the family. DUP appears to be a product of many forces such as denial of illness by patient and family, withdrawal and isolation from friends and relatives or negative symptoms with loss of motivation (McGlashan, 1999, Drake et al., 2000, Moller et al., 2000). Longer DUP may also be a correlate or byproduct of poor premorbid functioning. Haas and Sweeney (1992) demonstrated that poor premorbid functioning was correlated with longer DUP. Malla et al. (2002) reported a modest correlation between DUP and Premorbid Adjustment Scale (PAS) scores of early and late adolescence periods but not with mean PAS score. On the other hand, Loebel et al. (1992) and Larsen et al. (1996) did not find any correlation between DUP and premorbid adjustment levels.
Findings of the studies about the relationship between DUP and outcome of illness are still controversial. Several of these studies found significant inverse correlations between DUP and outcome (Black et al., 2001, Browne et al., 2000, Drake et al., 2000, Johnstone et al., 1986, Larsen et al., 2000, Loebel et al., 1992, Rabiner et al., 1986). In a recent study, Harrigan et al. (2003) reported that DUP predicted 12-month outcome independently of other variables. On the other hand some contrary results have also been reported (Barnes et al., 2000, Ho et al., 2000, Hoff et al., 2000).
However, relationship between DUP and short-term response to treatment on first admission was minimally explored. DUP was reported to be associated with more negative (Larsen et al., 1996) and positive symptoms (Kalla et al., 2002) at hospitalisation. Drake et al. (2000) also found that longer DUP predicts more severe symptoms on admission. However, Barnes et al. (2000) found no association between DUP and severity of illness or a resistance to treatment on first admission.
Premorbid social functioning has an impact on symptom severity and therapeutic outcome in first-episode psychosis. Rabinowitz et al. (2002) reported that poor premorbid functioning before onset of psychosis was associated with more severe symptoms and more severe cognitive manifestations of illness during the first episode. They found that patients with a stable–good premorbid functioning showed less negative symptoms and general psychopathology scores on the PANSS and also a lower score on CGI severity scale compared with the stable–poor premorbid functioning and deteriorating groups. Similarly, Kelley et al., 1992, Haas & Sweeney, 1992, Mukherjee et al., 1991, and Larsen et al. (1996) found associations between poorer premorbid functioning and negative symptoms on admission in first episode psychosis. Recent studies suggest that premorbid social functioning is also a crucial variable with regard to therapeutic outcome in first-episode. Amminger et al. (1997) have reported that patients with complete remission of positive symptoms after 8 weeks of pharmacotherapy had experienced far better premorbid adjustment in early adolescence and in childhood. Poor premorbid functioning was also found to be correlated with more negative symptoms at 1 year follow up in first episode psychosis (Larsen et al., 2000, Malla et al., 2002). In a recent study, Fresan et al. (2003) also reported that DUP was determined by premorbid functioning.
Part of the methodological problems in first episode research can be defined as retrospective quality of several studies and heterogeneity of diagnoses of the patients in the study group. Retrospective studies about the relationship between DUP and outcome of the illness have some methodological limits. The retrospective reviews involve many samples that are quite old and unevenly characterised diagnostically and demographically (McGlashan & Johannessen, 1996). On the other hand, patients with schizoaffective disorder, delusional disorder or brief reactive psychosis have also been included in some first episode studies (Drake et al., 2000, Larsen et al., 1996). Lack of consensus on the association of DUP with treatment response increases the importance of the investigations consisting of homogenous patient groups.
In order to explore prognostic significance of DUP, we examined its relation with changes in measures of symptom severity during acute treatment in a group of patients with first-episode schizophrenia. We hypothesised that DUP is inversely correlated with reduction in symptom severity at first hospitalisation. We also studied the relationship between premorbid adjustment levels and short-term response to treatment in first episode. The homogeneity of our relatively larger study group in terms of both diagnosis and treatment milieu, increases its importance among other studies.
Section snippets
Subjects
Subjects in this study were recruited from an ongoing prospective study, namely First-episode Schizophrenia Follow-up Project since 1996. Inclusion criteria for the current study were defined as: being in acute phase of their first psychotic episode, having an inpatient treatment and being between age of 15 and 45. Exclusion criteria were defined as: having any organic disorder known to cause psychosis or having alcohol and/or drug abuse.
Patients diagnosed as schizophrenia by means of the
Results
Sociodemographic variables and some of the clinical characteristics of our study group are given in Table 1. Measures of symptom severity like BPRS, SAPS and SANS on admission and discharge are also given in Table 2. There were significant intra-individual differences in BPRS (F=218.4, P=0.001), SAPS (F=140, P=0.001), and SANS scores (F=46.8, P=0.001) between admission and discharge.
DUP was not correlated with age at first episode and age at onset (r=−0.120, P=0.3 and r=0.101, P=0.6,
Discussion
This study suggests that longer DUP is related with worse outcome on first admission in patients with first-episode schizophrenia. Our findings also show that premorbid level of social functioning is associated with overall clinical severity on first admission but not with short-term response to treatment.
Median DUP was 6 months in our study, which fits well with other reports (Beiser et al., 1993, Drake et al., 2000, Loebel et al., 1992, Larsen et al., 2000). There was not any relation between
Acknowledgments
We would like to thank Professor Istvan Bitter, Semmelweis University, Budapest, Hungary for his valuable comments.
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2014, Psychiatry ResearchCitation Excerpt :There are many factors which have been considered influencing the response to treatment in first-episode schizophrenia. These factors include duration of untreated psychosis (DUP), premorbid adjustment in early adolescence and in childhood, social function, gender, marriage status, age of onset, severity of symptoms before treatment, ability to access psychiatry services substance use or not, and antipsychotic related parkinsonism during treatment (Breier et al., 1991; Amminger et al., 1997; Liu et al., 1997; Robinson et al., 1999; Uçok et al., 2004; Zhou and Xie, 2006; Crespo-Facorro et al., 2007; Emsley et al., 2007; Smelson et al., 2008; Suryani et al., 2011). But there is inconsistency of results between these studies.