Schizophrenia 22 Aug, 2023 Read Time: 4 mins

Debate continues on impact of duration of untreated psychosis on outcomes in psychosis

Duration of untreated psychosis (DUP) is defined as the time from manifestation of the first psychotic symptom to the initiation of treatment1. A symposium at the Schizophrenia International Research Society (SIRS) conference explored the association between DUP and illness prognosis.

DUP due to lead-time bias?

Dr. Katherine Jonas (Stony Brook University, USA) presented results from the Suffolk County Mental Health Project, a longitudinal study of schizophrenia in 287 patients with schizophrenia or schizoaffective disorder2. Investigators used the Premorbid Adjustment Scale (PAS) and Global Assessment of Functioning (GAF) scale to assess psychosocial functioning. They found that patients experienced similar declines in psychosocial functioning, regardless of duration of DUP. The difference was that those with a longer DUP experienced most of these declines prior to first admission, while those with a shorter DUP experienced them after first admission. The investigators conclude that DUP may be more useful to predict illness stage than outcome2.

Duration of untreated psychosis may be more useful to predict illness stage than outcome

Longer DUP associated with less recovery of function

Dr. Nikolai Albert (Copenhagen Research Center for Mental Health, Denmark) and his team applied a similar statistical approach used by Dr. Jonas to analyze data obtained from a previous study (OPUS)3. OPUS was a randomized controlled trial which tested the effect of specialized early intervention versus standard treatment in 578 patients with first episode of psychosis (FEP)3. Albert et al. assessed DUP using the Interview for the Retrospective Assessment of the Onset of Schizophrenia method in 496 patients. They also assessed psychosocial functioning using the PAS and GAF scales. Their model discovered that DUP was not associated with functioning at baseline, and onset of treatment occurred when participants’ level of functioning was most impaired3. A longer DUP was associated with a decrease in functioning for each additional week of DUP, and those with a longer DUP did not recover functioning to the same extent as those with a shorter DUP3.

A longer duration of psychosis is associated with a decrease in functioning for each additional week .

iHope study

iHope-20 is a prospective 20-year follow-up study of 171 individuals who had experienced FEP between 1995 and 1999 in South Dublin, Ireland4,5. At 20 years, 80 of the original cohort of 171 individuals were analyzed for follow-up. Investigators used three measures (Positive and Negative Syndrome Scale - PANSS, GAF and Quality of Life Scale) and ran mixed-model analyses to examine relationships of outcomes across time. Their analysis showed that DUP independently impacted 20-year outcomes5 and that relationships between shorter DUP and greater improvement were still evident 20 years post-FEP4. Dr. O’Keeffe speculatedththat reducing DUP may have clinical benefits that can last beyond 20 years following FEP4. He suggests that early treatment may help to give individuals the “psychological space” to recover, and that future studies should embrace a biopsychosocial approach, and also allow outcome measures to be “user defined".4

Reducing duration of untreated psychosis may have clinical benefits that can last beyond 20 years following first episode.

Cavan-Monaghan First Episode Psychosis Study (CAMFEPS)

Dr. John Waddington (Cavan-Monaghan Mental Health Service, Ireland) shared the findings6 of CAMFEPS, a study that compared the effects of duration of untreated illness (DUI) with those of DUP on 7-year outcomes following 163 cases of FEP in rural Ireland.  DUI is defined as the interval between appearance of first noticeable symptoms and initiation of antipsychotic treatment (vs DUP, which is based on first noticeable psychotic symptoms). Both longer DUI and DUP predicted more severe negative symptoms, reduced health related quality of life, lower functionality and lower service engagement. Longer DUI, but not DUP, predicted more severe positive and general symptoms. Neither longer DUP nor DUI predicted more severe cognitive impairment. Dr. Waddington concluded that because prediction of outcome by DUP appeared to be constant across seven years disproves the lead-time bias theory. He speculated that that reduction in DUI may be associated with more consistent and broader diminutions in impairment than for DUP.

Both longer duration of untreated illness and duration of untreated psychosis predicted more severe negative symptoms, reduced health related quality of life, lower functionality and lower service engagement.

Thus, the jury is still out as to the true impact of DUP on outcomes in psychosis. More prospective research is needed, with replication of results using consistent approaches to data analysis.

Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.

References

  1. Marshall M, Lewis S, Lockwood A et al. Association Between Duration of Untreated Psychosis and Outcome in Cohorts of First-Episode Patients. Arch Gen Psychiatry. 2005;62:975-983.
  2. Presented by Dr. Katherine Jonas at SIRS 2023, Toronto, Canada, May 12, 2023. Session Title: “The impact of duration of untreated psychosis on outcome: real world effect or phantom? Learning from landmark observational studies.”
  3. Presented by Dr. Nikolai Albert at SIRS 2023, Toronto, Canada, May 12, 2023. Session Title: “The impact of duration of untreated psychosis on outcome: real world effect or phantom? Learning from landmark observational studies.”
  4. Presented by Dr. Donal O’Keeffe at SIRS 2023, Toronto, Canada, May 12, 2023. Session Title: “The impact of duration of untreated psychosis on outcome: real world effect or phantom? Learning from landmark observational studies.”
  5. O’Keefe D, Hannigan A, Doyle R. The iHOPE-20 study: Relationships between and prospective predictors of remission, clinical recovery, personal recovery and resilience 20 years on from a first episode psychosis. ANZJP. 2019;53(11):1080-1092.
  6. Presented by Dr. John Waddington at SIRS 2023, Toronto, Canada, May 12, 2023. Session Title: “The impact of duration of untreated psychosis on outcome: real world effect or phantom? Learning from landmark observational studies.”