Linking PANSS negative symptom scores with the Clinical Global Impressions Scale: understanding negative symptom scores in schizophrenia

Stefan Leucht,Willie Earley,Balázs Szatmári,Erzsébet Szalai,Judit Harsányi,István Laszlovszky,Károly Acsai,Ágota Barabássy,György Németh

doi:10.1038/s41386-019-0363-2

Abstract

Understanding how rating scale improvement corresponds to a clinical impression in patients with negative symptoms of schizophrenia may help define the clinical relevance of change in this patient population. We conducted post hoc equipercentile linking analyses of Positive and Negative Syndrome Scale (PANSS) outcomes (e.g., PANSS-Factor Score for Negative Symptoms [FSNS]) with Clinical Global Impressions-Improvement (CGI-I) and -Severity (CGI-S) ratings on data from patients treated with cariprazine (n = 227) or risperidone (n = 229) in a clinical study evaluating negative symptoms in schizophrenia. Patients were prospectively selected for persistent, predominant negative symptoms of schizophrenia (PNS), and minimal positive/depressive/extrapyramidal symptoms. Linking results demonstrated that greater improvement on PANSS-derived measures corresponded to clinical impressions of greater improvement, as measured by the CGI-I, and less severe disease states, as measured by the CGI-S. For example, CGI-S scores of 1 (normal), 2, 3, 4, 5, and 6 (severely ill) corresponded to PANSS-FSNS scores of 7, 13, 19, 24, 29, and 35, respectively. Likewise, CGI-I scores of minimally improved, much improved, and very much improved corresponded to a change from baseline in PANSS-FSNS scores of −27%, −49%, and −100%, respectively. These are important findings for the interpretation of the results of trials in patients with persistent negative symptoms.

Highlights

Schizophrenia is a neuropsychiatric syndrome characterized by positive and negative symptoms, which reflect what is seen in the clinic and allow for categorization of symptoms into distinct symptom domains
Correlations were smaller in weeks 1 and 2 when changes on the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impressions (CGI) were still small and not necessarily in sync; the size of the correlations increased as the study progressed and changes on the scales corresponded
We performed post hoc equipercentile linking analyses on data from a clinical trial of cariprazine versus risperidone in patients selected for having stable schizophrenia and predominant negative symptoms of schizophrenia (PNS)

Summary

Introduction

Schizophrenia is a neuropsychiatric syndrome characterized by positive (i.e., hallucinations, delusions) and negative (i.e., blunted affect, anhedonia) symptoms, which reflect what is seen in the clinic and allow for categorization of symptoms into distinct symptom domains. Since most negative symptom improvement occurs in tandem with improvement in positive, depressive, or extrapyramidal symptoms (EPS), evaluating genuine treatment effect on negative symptoms requires a well-designed trial in a patient population prospectively selected for primary and persistent negative symptoms. In drug research in schizophrenia, treatment effect is routinely determined by mean change in score on a symptom-based rating scale, such as the Positive and Negative Syndrome Scale (PANSS) [3]. Since most trials that assess negative symptoms include patients with positive symptoms, negative symptom improvement that occurs secondarily to changes in positive or depressive symptoms is prone to ambiguous interpretation [6]. Understanding negative symptoms that improve independently of improvement in other symptom domains and represent genuine treatment effect could help advance an understanding of what constitutes clinically meaningful change in patients with schizophrenia

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