Duration of untreated psychosis (DUP) and the course of schizophrenia in a 20-year follow-up study

Abstract

Our aims were to analyze the relationship between the duration of psychosis (DUP) and short- and long-term outcomes of treatment, and to determine the cut-off point between short and long DUP at which differences in treatment outcomes are most significant. We assessed 80 participants with schizophrenia at the point of their first hospitalization. Fifty participated in all four follow-ups over 20 years. DUP was divided into short (up to 6 months) and long (over 6 months). ANOVA and Chi-square tests were employed to identify significant differences in both clinical and social indicators of functioning. ROC curves were used to estimate the best DUP division point. Significant differences favoring the short-DUP group were found for: GAF, total severity of symptoms and severity of positive symptoms, social functioning measured according to DSM-III criteria, employment, and social contacts. The optimal cut-off point for DUP was the 23rd week. We concluded that: (1) the relationship between longer DUP and worse overall treatment outcomes was sustained throughout the 20 years, (2) a positive correlation between DUP and the severity of psychopathological symptoms was observed over the first 12 years of illness, (3) the results indicate the efficacy of early therapeutic interventions in psychosis.

Introduction

In recent years, the criterion of duration of untreated psychosis (DUP) has risen to prominence as one of the fundamental factors determining prognosis in the course of schizophrenia-related psychotic disorders. Two meta-analyses (Marshall et al., 2005, Perkins et al., 2005) describing the results of research into the correlation between DUP and the course of illness and treatment outcomes unequivocally indicate the existence of a positive correlation, confirmed primarily by the aggregate results of numerous short-term studies (involving up to 5 years of observation). The first of these meta-analyses (Marshall et al., 2005) indicates a positive correlation between longer DUP and worse treatment outcomes in terms of general functioning, positive symptoms, and quality of life, but not between longer DUP and negative symptoms or social functioning. The second meta-analysis (Perkins et al., 2005) demonstrates a positive correlation between shorter DUP and better response to treatment—lesser severity of general psychopathology, positive and negative symptoms, and better general functioning. A significant meta-analysis concerning the relationship between DUP and negative symptoms in the short and medium term was conducted by Boonstra et al. (2012) Contrary to previous reports, it shows that there is an association between those areas. Based on a review of studies from the years 1992–2009, Boonstra found that a shorter DUP is associated with lesser severity of negative symptoms in both short-term (1–2 years) and medium-term (5–8 years) studies. The decrease in the severity of negative symptoms was non-linear. A DUP shorter than 9 months markedly increased the chances of less severe negative symptoms in follow-ups.

Prospective studies which begin with the first episode of psychosis (FEP) and assess the effect of DUP on remote treatment outcomes (over 10 years) are rarer. Our study falls into this category. It is a prospective study beginning at the point of first psychiatric hospitalization (real time), and it is long-term in duration (as per McGlashan (1988)): running over 10 years). We shall make reference to other studies fulfilling the same criteria—by Helgason (1990), Huber (1997), Wiersma et al. (2000), Kua et al. (2003), Bottlender et al. (2003), Röpcke and Eggers (2005), Kinoshita et al. (2005), White et al. (2009), Shirvastava et al. (2010), Ichinose et al. (2010), and Cechnicki et al. (2010). In these studies, the period of observation ranges from 10 to 28 years. The results of most of these studies indicate the existence of a correlation between DUP and remote treatment outcomes, although several of them present disparate results.

Diverse criteria have been adopted to divide DUP into short- and long-term, and various definitions of the end of DUP (e.g. psychiatric hospitalization, making contact with a therapist, starting to take neuroleptics, etc.) have been offered. Some of the studies (Helgason, 1990, Huber, 1997; Bottlender et al., 2003) did not include any intermediate assessment points, which makes assessment of the dynamics of potential changes over time difficult. In the studies (Huber, 1997, Wiersma et al., 1998, Wiersma et al., 2000, Kua et al., 2003), DUP analysis is included as one of many aspects of long-term catamnestic study, and the assessment is usually restricted to the influence of DUP on clinical outcomes. In the wake of ambiguous results, answers to three questions remain unsettled. First, is there a correlation between DUP and long-term outcomes in both clinical and social functioning over the course of many years of illness (in our case, 20)? Second, does this relationship remain constant over the years, or do the differences between the short- and long-DUP subgroups tend to fluctuate over time? Third, is there a cut-off point enabling us to define a period of untreated psychosis beyond which the treatment outcomes for schizophrenic psychoses (schizophrenia) tend to deteriorate markedly, and if so, what is it?