Innovations In Clinical Neuroscience

NOV-DEC 2017

A peer-reviewed, evidence-based journal for clinicians in the field of neuroscience

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41 ICNS INNOVATIONS IN CLINICAL NEUROSCIENCE November-December 2017 • Volume 14 • Number 11–12 O R I G I N A L R E S E A R C H T The Positive and Negative Syndrome Scale (PANSS) in schizophrenia (SZ) is a commonly used tool to evaluate psychiatric symptoms, providing a metric by which treatment effectiveness can be gauged. 1 The full scale consists of 30 items assessing symptoms, such as Conceptual Disorganization, Hallucinatory Behavior, and Blunted Affect, as judged by trained raters on a 7-point ordered scale . These item ratings are commonly summed to yield an overall symptom severity score that in turn is used to judge change in symptoms after treatment. PANSS item ratings also have been used to evaluate changes in clinical status, including remission of symptoms. The Remission in Schizophrenia Working Group previously identified 8 of the 30 PANSS symptoms for which "remission" could be benchmarked. 2 The workgroup defined remission as a "state in which patients have experienced an improvement in core signs and symptoms to the extent that any remaining symptoms are of such low intensity that they no longer interfere significantly with behavior and are below the threshold typically utilized in justifying an initial diagnosis of schizophrenia." Remission also has been described to be a "more stringent standard than [treatment] response. 2 Specifically, the workgroup defined remission in SZ by scores of 3 or less (mild) on eight specific PANSS items: Delusions, Unusual Thought Content, Hallucinatory Behavior, Conceptual Disorganization, Mannerisms/Posturing, Blunted Affect, Social Withdrawal, and Lack of Spontaneity and Flow of Conversation. 2 In this study, this 8-item subset will be referred to as the "Remission set." A B S T R A C T Objective: Total scale scores derived by summing ratings from the 30-item PANSS are commonly used in clinical trial research to measure overall symptom severity, and percentage reductions in the total scores are sometimes used to document the efficacy of treatment. Acknowledging that some patients may have substantial changes in PANSS total scores but still be sufficiently symptomatic to warrant diagnosis, ratings on a subset of 8 items, referred to here as the "Remission set," are sometimes used to determine if patients' symptoms no longer satisfy diagnostic criteria. An unanswered question remains: is the goal of treatment better conceptualized as reduction in overall symptom severity, or reduction in symptoms below the threshold for diagnosis? We evaluated the psychometric properties of PANSS total scores, to assess whether having low symptom severity post-treatment is equivalent to attaining Remission.Design: We applied a bifactor item response theory (IRT) model to post-treatment PANSS ratings of 3,647 subjects diagnosed with schizophrenia assessed at the termination of 11 clinical trials. The bifactor model specified one general dimension to reflect overall symptom severity, and five domain-specific dimensions. We assessed how PANSS item discrimination and information parameters varied across the range of overall symptom severity (θ), with a special focus on low levels of symptoms (i.e., θ<-1), which we refer to as "Relief " from symptoms. A score of θ=-1 corresponds to an expected PANSS item score of 1.83, a rating between "Absent" and "Minimal" for a PANSS symptom. Results: The application of the bifactor IRT model revealed: (1) 88% of total score variation was attributable to variation in general symptom severity, and only 8% reflected secondary domain factors. This implies that a general factor may provide a good indicator of symptom severity, and that interpretation is not overly complicated by multidimensionality; (2) Post-treatment, 534 individuals (about 15% of the whole sample) scored in the "Relief " range of general symptom severity, but more than twice that number (n = 1351) satisfied Remission criteria (37%). 2 in 3 Remitted patients had scores that were not in a low symptom range (corresponding to Absent or Minimal item scores); (3) PANSS items vary greatly in their ability to measure the general symptom severity dimension; while many items are highly discriminating and relatively "pure" indicators of general symptom severity (delusions, conceptual disorganization), others are better indicators of specific dimensions (blunted affect, depression). The utility of a given PANSS item for assessing a patient depended on the illness level of the patient. Conclusion: Satisfying conventional Remission criteria was not strongly associated with low levels of symptoms. The items providing the most information for patients in the symptom Relief range were Delusions, Preoccupation, Suspiciousness Persecution, Unusual Thought Content, Conceptual Disorganization, Stereotyped Thinking, Active Social Avoidance, and Lack of Judgment and Insight. Lower scores on these items (item scores ≤2) were strongly associated with having a low latent trait θ or experiencing overall symptom relief. The inter-rater agreement between Remission and Relief subjects suggested that these criteria identified different subsets of patients. Alternative subsets of items may offer better indicators of general symptom severity and provide better discrimination (and lower standard errors) for scaling individuals and judging symptom relief, where the "best" subset of items ultimately depends on the illness range and treatment phase being evaluated. KEYWORDS: Schizophrenia, PANSS, symptom relief, remission, item response theory Disparity between General Symptom Relief and Remission Criteria in the Positive and Negative Syndrome Scale (PANSS): A Post-treatment Bifactor Item Response Theory Model by ARIANA E. ANDERSON, PhD; STEVEN P. REISE, PhD; STEPHEN R. MARDER, MD; MAXWELL MANSOLF, MS; CAROL HAN, BS; and ROBERT M. BILDER, PhD Dr. Anderson is with the Department of Psychiatry and Biobehavioral Sciences and the Department of Statistics, Dr. Reise is with the Department of Psychology, Dr. Marder is with the Department of Psychiatry and Biobehavioral Sciences, Mr. Mansolf is with the Department of Psychology, Ms. Han is with the Department of Psychiatry and Biobehavioral Sciences, and Dr. Bilder is with the Department of Psychiatry and Biobehavioral Sciences and the Department of Psychology—all from the University of California Los Angeles, Los Angeles, California. Innov Clin Neurosci. 2017;14(11–12):41–53 FUNDING: This work was supported by sponsored research to UCLA by Janssen Research & Development, LLC and the National Institutes of Health (NIH)—(National Institute of Mental Health UL1DE019580, R01MH101478, PL1MH083271 to RB, R03MH106922 to RB and AA; and by the National Institute on Aging K25AG051782 to AA.) Dr. Anderson holds a Career Award at the Scientific Interface from BWF. DISCLOSURES: The authors have no financial conflicts relevant to the content of this article. CORRESPONDENCE: Ariana Anderson, PhD; Email: ArianaAnderson@mednet.ucla.edu

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