Duration of untreated psychosis and negative symptoms--a systematic review and meta-analysis of individual patient data.

Background: Longer duration of untreated psychosis (DUP) is associated with poorer outcome in terms of positive symptoms, relapse rate, and time to remission. In contrast, the association with negative symptoms is less consistent.

Aims: The study had three aims. First, to arrive at a more precise estimate of the correlation between DUP and negative symptoms than previous reviews, by substantially increasing the amount of available data. Second, to see whether the strength of this correlation attenuated over longer follow-up intervals. Third, to determine whether there is a relationship between DUP and changes in negative symptoms.

Method: Relevant databases were searched for studies published between December 1992 and March 2009 that reported data on DUP and negative symptoms. We obtained individual patient data where possible and calculated summary correlations between DUP and negative symptoms for each study at baseline, short and long-term follow-up. We used multilevel regression analysis to examine whether the effect of DUP on negative symptoms was the greatest in the early stages of illness.

Results: We included 28 non-overlapping studies from the 402 papers detected by the search strategy. After contacting the authors we obtained individual patient data from 16 of these studies involving 3339 participants. The mean DUP was 61.4 weeks (SD=132.7, median DUP=12.0). Shorter DUP was significantly associated with less severe negative symptoms at baseline and also at short (1-2 years) and longer term follow-up (5-8 years) (r=0.117, 0.180 and 0.202 respectively, p<0.001). The relationship between improvement in negative symptoms and DUP was found to be non-linear: people with a DUP shorter than 9 months showed substantially greater negative symptom reduction than those with a DUP of greater than 9 months.

Conclusions: Shorter DUP is associated with less severe negative symptoms at short and long-term follow up, especially when the DUP is less than 9 months. Since there is no effective treatment for negative symptoms, reducing DUP to less than 9 months may be the best way to ameliorate them.