Duration of untreated psychosis (DUP) marks the period from when psychotic symptoms first appear to when treatment starts. A longer DUP predicts worse outcomes, including more severe symptoms, more frequent relapses, treatment refractoriness, and poorer global functioning (Penttilä M et al, Br J Psychiatry 2014;205(2):88–94). By identifying new-onset psychosis and intervening early, we can dramatically improve patients’ outcomes.

Even a brief delay in treatment of psychosis—mere weeks—can have profound and enduring negative effects on a patient’s illness trajectory. A study with over 1,200 participants demonstrated that a tenfold increase in DUP, such as from 10 to 100 days, significantly worsened patient outcomes, akin to receiving a placebo instead of active treatment, even after treatment was eventually initiated (Drake RJ et al, Lancet Psychiatry 2020;7(7):602–610). The authors noted that the most significant decrease in treatment efficacy occurred in the initial weeks following the onset of psychosis. Another study that followed 50 patients over 20 years found sustained significant differences in symptom severity and social functioning between those with a DUP of less than six months and those with a DUP of more than six months, emphasizing the long-term impact of early treatment (Cechnicki A et al, Psychiatry Res 2014;219:420–425).

Extended DUP also poses a heightened risk of suicidality during the early stages of psychosis. Research from Norway involving 170 patients with first-episode psychosis found that a quarter of the patients made a suicide attempt over the course of the study, with more than half of these attempts occurring during the period of untreated psychosis. Prolonged DUP was associated with an increased risk of suicide during this period (Barrett EA et al, Schizophr Res 2010;119(1–3):11–17).

Why does greater DUP have such adverse consequences on patients’ outcomes? Neuroimaging studies to identify global structural or functional neurotoxicity associated with DUP but have found preliminary evidence suggesting that DUP may impact temporal areas of the brain (Zoghbi AW et al, Mol Psychiatry 2022;28(1):168–190). The deteriorations could stem from neurobiological alterations, like variations in synaptic density, that have not yet been identified.

Might patients with prolonged DUP differ from those with shorter DUP in certain ways, such as poorer insight or a more insidious onset of psychosis? Research studies have attempted to address this question by using statistical adjustments and matching techniques to account for variables like age, gender, and initial symptom severity. But even the most sophisticated research methods cannot entirely eliminate the possibility of underlying confounding factors. Nevertheless, given the significant stakes involved in patients’ treatment outcomes and the relatively achievable goal of early intervention, it makes sense to implement early treatment strategies for patients experiencing first-onset psychosis. Supporting this approach, a recent Cochrane review of randomized clinical trials found that intensive early intervention for psychosis offers several benefits compared to treatment as usual, including improvements in global function and potential reductions in psychiatric hospitalizations (Puntis S et al, Cochrane Database of Systematic Reviews 2020;11).

Early intervention in psychosis

Several programs have arisen around the country that seek to improve access to care for those experiencing a first episode of psychosis. Some provide education about psychosis, its treatment, and care pathways for school health centers and other providers who may be the first to contact at-risk youth. The Early Psychosis Intervention Network (EPINET) includes over 100 clinics across several states and is comprised of:

• Individual or group psychotherapy
• Family support and education
• Psychotropic medication management
• Vocational and educational support
• Case management services

These early interventions are associated with reduced psychotic and negative symptoms, decreased substance use, and enhanced social functioning and patient satisfaction compared to usual care. If there is an EPINET program near you, take advantage of it. You can find ­EPINET-affiliated clinics and other resources at https://nationalepinet.org. If you do not have access to such a resource:

• Educate patients and families about the potential chronicity of the condition. Emphasize the reduced risk of future psychotic episodes if they adhere to treatment.
• Normalize and encourage treatment with long-acting injectable antipsychotics. Initiate treatment prior to discharge to reduce risk of relapse and treatment nonadherence.
• Discuss the role of substance use, in particular cannabis and psychostimulants, in the exacerbation of psychosis and the importance of abstaining from such drug use.
• Coordinate close outpatient psychiatric follow-up at a well-resourced clinic that offers psychotherapy, family support, and case management.

CARLAT VERDICT 

Start treatment as early as possible in patients with new onset psychosis, as the longer the delay in initiating treatment, the less effective the treatment becomes. Educate patients and families about these findings to help overcome the reluctance about treatment that is so common in first-episode cases of psychosis and take advantage of early intervention programs if they’re available in your area.