Rethinking ‘persistence’ in negative symptoms for better functional recovery

Even short-term persistence of negative symptoms is associated with reduced clinical and real-life functional outcomes in recent-onset psychosis - negative symptoms need early effective treatment to improve long-term, real-life functioning.

Patients with first-episode schizophrenia and persistent negative symptoms (PNS) have worse outcomes at one year compared with those without PNS.1

PNS have been defined as unconfounded negative symptoms of at least moderate severity that persist for at least six months in the absence of high levels of positive, depressive and extrapyramidal symptoms.2


Short-term persistence of negative symptoms associates with poor outcome

Even short-term persistence of negative symptoms has a significant effect on remission and resistance to treatment

In her presentation at EPA Virtual 2021, Professor Armida Mucci, University of Naples, Italy, revealed that in patients with recent-onset psychosis, even short-term persistence of negative symptoms has a significant effect on remission and resistance to treatment.3

In the OPTiMiSE trial, treatment response and adherence was assessed at 4, 10, and 22 weeks of follow-up in patients with negative symptoms at baseline that persisted, compared with patients with non-PNS (in whom negative symptoms did not persist or were confounded at baseline; N-PNS).3

‘Persistence’ in negative symptoms can mean just a few weeks

For patients with PNS, the rate of remission was significantly lower than for those with N-PNS at all follow-up visits. Even as early as 4 weeks, patients with PNS had a significantly lower rate of remission than those with N-PNS (p<0.0001). There was also a higher dropout rate at weeks 10 and 22 for patients with PNS compared to those with N-PNS.3


Remission of negative symptoms key for real-life function

Without remission of negative symptoms, the chance of remaining in employment is low

Professor Merete Nordentoft, University of Copenhagen, Denmark, reported the negative implications of PNS in early-stage illness, highlighting that remission of negative symptoms may be the key to improving employment outcomes.

In a study evaluating patients with early-stage schizophrenia conducted over a 42-month period, it was found that while remission of both positive and negative symptoms was the most positive indicator for remaining in competitive employment, remission of negative symptoms only was more important than remission of positive symptoms only, and that, without negative symptom remission, only 10% of patients remained in employment over the period studied.4

In contrast to responses for positive symptoms, which tend to follow a more heterogenous path, the trajectory of negative symptoms is less variable over the long term, indicating that treating negative symptoms at an early stage may have positive implications for long-term outcomes.5


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.


1. Galderisti S et al. Eur Neuropsychopharmacol 2013;23:196-204

2. Buchanan W. Schizophr Bull 2007;33:1013-22

3. Bucci P et al. Eur Neuropsychopharmacol 2020;34:76-86

4. Albert, 2017. PhD thesis

5. Austin SF et al. Schizophr Res 2015;168:84-91


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