Abstract
OBJECTIVES: Negative symptoms in schizophrenia are associated with significant illness burden. We sought to investigate clinical outcomes for patients with schizophrenia who present with predominant negative symptoms (PNS) vs without PNS. DESIGN: Retrospective analysis of electronic health record (EHR) data. SETTING: 25 US providers of mental healthcare. PARTICIPANTS: 4444 adults with schizophrenia receiving care between 1999 and 2020. EXPOSURE: PNS defined as ≥3 negative symptoms and ≤3 positive symptoms recorded in EHR data at the time of the first recorded schizophrenia diagnosis (index date). Symptom data were ascertained using natural language processing applied to semistructured free text records documenting the mental state examination. A matched sample (1:1) of patients without PNS was used to compare outcomes. Follow-up data were obtained up to 12 months following the index date. PRIMARY OUTCOME MEASURE: Mean number of psychiatric hospital admissions. SECONDARY OUTCOME MEASURES: Mean number of outpatient visits, estimated treatment costs, Clinical Global Impression - Severity score and antipsychotic treatments (12 months before and after index date). RESULTS: 360 (8%) patients had PNS and 4084 (92%) did not have PNS. Patients with PNS were younger (36.4 vs 39.7 years, p<0.001) with a greater prevalence of psychiatric comorbidities (schizoaffective disorders: 25.0 vs 18.4%, p=0.003; major depressive disorder: 17.8 vs 9.8%, p<0.001). During follow-up, patients with PNS had fewer days with an antipsychotic prescription (mean=111.8 vs 140.9 days, p<0.001). Compared with matched patients without PNS, patients with PNS were more likely to have a psychiatric inpatient hospitalisation (76.1% vs 59.7%, p<0.001) and had greater estimated inpatient costs ($16 893 vs $13 732, p=0.04). CONCLUSIONS: Patients with PNS were younger and presented with greater illness severity and more psychiatric comorbidities compared with patients without PNS. Our findings highlight an unmet need for novel therapeutic approaches to address negative symptoms to improve clinical outcomes.