Duration of untreated psychosis an 'important prognostic factor' at first presentation
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Duration of untreated psychosis may serve as an important prognostic factor at first presentation, as well as predict clinically relevant outcomes over the course of illness, according to study results published in World Psychiatry.
“Many mental health services devote significant resources to early intervention in psychosis based, at least partly, on the premise that reducing [duration of untreated psychosis] improves outcomes,” Oliver D. Howes, MRCPsych, PhD, of the Institute of Psychiatry, Psychology and Neuroscience at King’s College London, and colleagues wrote. “This notion has been investigated in over a hundred studies examining a number of different outcomes, summarized in several meta-analyses. However, due to the inclusion of overlapping samples in different meta-analyses, and differences in inclusion criteria, definition of outcomes, reporting standards and analysis techniques, it is difficult to generate a clear hierarchy of evidence.”
Moreover, the researchers noted that analyses at first presentation have all included mixed samples of antipsychotic naïve and treated participants, meaning these analyses did not delineate the effects of duration of untreated psychosis on outcomes among antipsychotic naïve participants.
In the current umbrella review and random-effects meta-analysis, Howes and colleagues aimed to classify evidence to inform the planning and targeting of interventions for duration of untreated psychosis reduction. They searched four databases from inception to Sept. 3, 2020, for relevant meta-analyses of studies that included individuals with schizophrenia spectrum disorders, first-episode psychosis or affective and non-affective psychosis. They include 13 meta-analyses that corresponded to 129 individual studies and a sample size of 25,657 individuals. However, they noted some of the meta-analyses had potential violations of statistical assumptions and thus conducted a new random-effects meta-analysis of primary studies, grading the link between duration of untreated psychosis and each outcome per a standardized classification into convincing, highly suggestive, suggestive, weak or non-significant.
Results showed suggestive evidence at first presentation for an association between longer duration of untreated psychosis and more severe negative symptoms, as well as increased risk for previous self-harm. The researchers found highly suggestive evidence at follow-up for an association between longer duration of untreated psychosis and more severe positive symptoms, more severe negative symptoms and lower likelihood of remission, as well as suggestive evidence for an association between longer duration of untreated psychosis and poorer overall functioning and more severe global psychopathology. Upon restricting analysis to prospective studies, results remained unchanged. Howes and colleagues noted the clinically meaningful nature of these effect sizes, with a duration of untreated psychosis of four weeks predicting greater than 20% more severe symptoms at follow-up relative to a duration of untreated psychosis of 1 week.
“Future work should also investigate the mechanisms which may underlie the relationship between [duration of untreated psychosis] and outcomes, explore the effect of [duration of untreated psychosis] in antipsychotic naïve patients and control for potential confounders, particularly interrelated outcome variables, mode of presentation and diagnosis, to allow clearer inferences on causation to be drawn,” the researchers wrote.