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Dear Colleagues:

Thirty years ago, the Positive and Negative Syndrome Scale (PANSS) was developed and published by Stanley Kay, Abraham Fiszbein, and Lewis Opler to identify the presence and severity of psychopathology symptoms in patients with psychotic disorders, with the objective of measuring patient characteristics and evaluating change over time using 30 symptoms rated on a 7-point scale.1 The rationale behind the creation of the PANSS was to include items that best represent positive, negative, and general symptom characteristics and to exclude others, such as attentional disorders, which might be secondary to other symptoms. Although the PANSS was originally developed for use in schizophrenia, it is also used regularly for measuring treatment response in other conditions, including bipolar disorder,2 schizoaffective disorder,3 agitation across the psychosis spectrum,4 anorexia nervosa,5 substance use disorders,6 and many other diseases. Since its initial publication, the PANSS has been administered in thousands of clinical trials across the globe to millions of individuals and has been approved by the United States Food and Drug Administration (FDA) as a primary endpoint for multiple disorders.

The psychometric properties of the PANSS have been thoroughly studied in several publications over the past 30 years. Strong psychometric properties in terms of reliability, validity, and sensitivity have been shown in several studies. Studies examining the psychometric properties of the PANSS have focused on methods from classical test theory and modern psychometric techniques (e.g., item response analysis). However, the clinical implications of the total PANSS score are still somewhat uncertain outside of research settings. Furthermore, in clinical studies, a reduction of at least 20 to 50 percent of the initial PANSS score has been used to define response to treatment, but what these cut-offs mean from a global perspective—and from a patient perspective—is still ambiguous.

In the decades since it was published, however, important changes in the clinical research landscape have taken place that necessitate a re-examination of the PANSS. In 2010, the Research Domains Criteria (RDoC) initiative was launched to help overcome limitations in the existing diagnostic taxonomy by investigating “new ways of classifying mental disorders based on dimensions of observable behavior and neurobiological measures.”7 The promise of RDoC is that it might provide dimensions that are more tractable with respect to ultimate links to more basic biological processes on the one hand, while maintaining relations to symptoms and mental disorder. Another trend that might impact clinical assessment is the demand that research efforts incorporate a patient-centric approach and take values and conditions critical to patients and caregivers into account.8 Similarly, the movement toward measure-based care might also have reciprocal impacts on adoption and evolution of rating scales.9

In this issue of Innovations in Clinical Neuroscience, we reflect on the origins of the PANSS, but also on its future from a variety of perspectives, exploring both the limitations of the scale and methods for improving and adapting it to the 21st century landscape. We challenged contributors to consider several critical questions, including what the role of symptom-based assessments and clinician-reported outcome scales should be. How well does the PANSS rise to challenges posed by an evolving psychopharmacology and neurobiology of mental illness? Are clinical assessment measures archaic and replaceable by other modalities, or should advances in the disease area also yield to advances in measurement? As such, can modern statistical approaches adequately refine the PANSS to produce more psychometrically sound trans-diagnostic measurements of treatment efficacy, with or without the contributions of other measurement sources? For example, within the past 10 years, analytic approaches have been implemented to assess the quality of individual PANSS items across varying levels of symptom severity, across different cultures, and across geographical regions. 

Within this collection of articles, we begin to get a sense of what the next 30 years might look like, both for the PANSS and for the art and science of clinical assessment. From historical reviews discussing the bases of its global adoption during the late 20th century to the potential for adaptation and evolution in the 21st century.

We offer our thanks to all the contributors and reviewers who offered their time and energy to this endeavor, to the International Society of CNS Clinical Trials Methodology (ISCTM) for providing the intellectual environment that spawned this exciting discussion, and to the publishing staff of ICNS for their exceptional talent and devotion to this important work.

With regards,

Guest Co-Editors

Mark G. A. Opler, PhD, MPH

Adjunct Assistant Professor, NYU School of Medicine; Chief Research Officer, MedAvante-ProPhase New York, New York.

Anzalee Khan, PhD

Senior Biostatistician, NeuroCog Trials; Psychopharmacology Research Program, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York

Ariana Anderson, PhD

Department of Psychiatry and Biobehavioral Sciences, Department of Statistics, University of California Los Angeles, Los Angeles, California


  1. Kay SR, Fiszbein A, Opler LA.The Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Schizophr Bull. 1987;13(2):261–76.
  2. Potkin SG, Keck PE Jr, Segal S, et al. Ziprasidone in acute bipolar mania: a 21-day randomized, double-blind, placebo-controlled replication trial. J Clin Psychopharmacol. 2005;25(4):301–10.
  3. Janicak PG, Keck PE Jr, Davis JM, et al. A double-blind, randomized, prospective evaluation of the efficacy and safety of risperidone versus haloperidol in the treatment of schizoaffective disorder. J Clin Psychopharmacol. 2001;21(4):360–8
  4. Baker RW, Kinon BJ, Maguire GA, et al. Effectiveness of rapid initial dose escalation of up to forty milligrams per day of oral olanzapine in acute agitation. J Clin Psychopharmacol. 2003;23(4):342–8.
  5. Powers PS, Bannon Y, Eubanks R, McCormick T. Quetiapine in anorexia nervosa patients: an open label outpatient pilot study. Int J Eat Disord. 2007 Jan;40(1):21–6.
  6. Alexander PD, Gicas KM, Willi TS, et al. A comparison of psychotic symptoms in subjects with methamphetamine versus cocaine dependence. Psychopharmacology (Berl). 2017 May;234 (9–10):1535–1547.
  7. Insel T, Cuthbert B, Garvey M, et al. Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. Am J Psychiatry. 2010 Jul;167(7):748–51.
  8. Lamberti MJ, Awatin J. Mapping the landscape of patient-centric activities within clinical research. Clin Ther. 2017 Oct 9. pii: S0149–2918(17)30984-0
  9. Fortney JC, Unützer J, Wrenn G, et al. A tipping point for measurement-based care. Psychiatr Serv. 2017;68(2): 179–188.

Table of Contents

Precursors to the PANSS: The BPRS and its progenitors

A Developmental History of the Positive and Negative Syndrome Scale (PANSS)

Using the Positive and Negative Syndrome Scale (PANSS) to Define Different Domains of Negative Symptoms: Prediction of Everyday Functioning by Impairments in Emotional Expression and Emotional Experience

Disparity between General Symptom Relief and Remission Criteria in the Positive and Negative Syndrome Scale (PANSS): A Post-treatment Bifactor Item Response Theory Model

Understanding Antipsychotic Drug Treatment Effects: A Novel Method to Reduce Pseudospecificity of the Positive and Negative Syndrome Scale (PANSS) Factors

Sensitivity of the Positive and Negative Syndrome Scale (PANSS) in Detecting Treatment Effects via Network Analysis

Bridging the Measurement Gap Between Research and Clinical Care in Schizophrenia: Positive and Negative Syndrome Scale-6 (PANSS-6) and Other Assessments Based on the Simplified Negative and Positive Symptoms Interview (SNAPSI)

Are Shorter Versions of the Positive and Negative Syndrome Scale (PANSS) Doable? A Critical Review

Positive and Negative Syndrome Scale (PANSS) Training: Challenges, Solutions, and Future Directions

Insight and Treatment Outcomes in Schizophrenia: Post-hoc Analysis of a Long-term, Double-blind Study Comparing Lurasidone and Quetiapine XR

Negative Symptom Dimensions of the Positive and Negative Syndrome Scale Across Geographical Regions: Implications for Social, Linguistic, and Cultural Consistency