Innovations In Clinical Neuroscience

NOV-DEC 2017

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

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75 ICNS INNOVATIONS IN CLINICAL NEUROSCIENCE November-December 2017 • Volume 14 • Number 11–12 R E V I E W extracted six items from the full PANSS with the aim of developing a brief scale that could be administered within 10 minutes and be sensitive to changes resulting from antipsychotic treatment. 19 The authors aimed at selecting at least two specific items from each of the three PANSS subscales (i.e., the positive symptoms, negative symptoms, and general psychopathology scales) to sufficiently reflect the profiles of schizophrenia. All selected items had to have high levels of correlation with changes in the Clinical Global Impression (CGI-I) scale that reflected their sensitivity to change, as well as high levels of correlation with the CGI-S scale that reflected the severity of illness. Data was derived from 714 patients with schizophrenia involved in antipsychotic trials. The six items were Delusion, Suspiciousness, Emotional Withdrawal, Passive/Apathetic Social Withdrawal, Tension, and Unusual Thought Content. The Brief PANSS showed a high correlation of 0.86 with the full PANSS at study entry and 0.92 at the end of antipsychotic treatment. The correlation between the change as measured with the Brief PANSS and with the total PANSS was 0.93 (p<0.001), while the correlation of change measured with the Brief PANSS and the change in the CGI scale score was 0.73 (p<0.001). Similar to the Mini- PANSS, the Brief PANSS has not yet undergone psychometric testing regarding its construct validity and reliability with respect to its use in patient samples other than the original study population used in the development of the Brief PANSS. The six-item PANSS. Ostergaard et al 18 have presented a six-item PANSS (PANSS-6) based on the Rasch rating scale model that comprises the scalable items Delusions, Conceptual Disorganization, Hallucinations, Blunted Affect, Social Withdrawal, and Lack of Spontaneity and Flow of Conversation. 18 The Rasch rating model indicated that the three scalable items (all items provide unique information regarding syndrome severity) covering positive symptom items (Delusions, Conceptual Disorganization, and Hallucinations) had the highest prevalence, whereas the three scalable negative items (Blunted Affect, Social Withdrawal, and Lack of Spontaneity and Flow of Conversation) had the lowest prevalence. Furthermore, the PANSS-6 was shown by the authors to be sensitive to change in patients in two antipsychotic trials (haloperidol and sertindole versus placebo 18 ) and to differentiate the active treatment symptom reduction from the placebo symptom reduction. The remission rate as measured by the PANSS-6 was defined at less than 14, when using a CGI scale score of 3 or less as an index of validity for remission. Using this cutoff point, the PANSS-6 also measured higher remission rates during treatment with haloperidol and sertindole versus placebo. The authors support the construct validity of the PANSS-6 by the observation that it covers four of the five symptoms included as criteria for schizophrenia (except for "Grossly Disorganized or Catatonic Behavior") according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition 19a (DSM-5). In a more recent study that tested the validity and sensitivity of the PANSS-6 in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study, 19b Ostergaard et al 20 reanalyzed the 1,432 subjects (intention-to-treat [ITT] sample) and found that the PANSS-6 and PANSS-30 total scores were highly correlated (Spearman correlation coefficient=0.86). However, these investigators did not remove from the PANSS-30 the items from the PANSS-6, resulting in error variance of these six correlated items and inflation of the reported correlations. The same limitation affects the reported high correlations between PANSS-6 and PANSS-30 for the relative changes in total scores (Spearman correlation coefficient=0.77), between the total score ratios (Spearman correlation coefficient=0.77), and between the total score log-ratios (Spearman correlation coefficient=0.77). The PANSS-6 identified symptom remission with an accuracy of 0.99 (95% confidence interval [CI]=0.99–0.99). In ITT analyses, PANSS-6 and PANSS-30 identified the same statistically significant differences in antipsychotic efficacy (i.e., that olanzapine was superior to risperidone [p-value for PANSS-6 was 0.0003 and for PANSS-30 was 0.0003] and ziprasidone [p-value for PANSS-6 was 0.0018 and for PANSS-30 was 0.0046). Psychometric testing of the PANSS-6 needs to be expanded to prospective testing of its sensitivity to change and its use in longitudinal remission studies. CONCLUSION Reducing the burden of administration would be a key advantage the shorter PANSS would have over the PANSS-30, for clinicians, researchers, and patients. There are newer scales available that have a reduced number of original PANSS items. The PANSS-14 and PANSS-19 are scales based on IRT application with inclusion of psychometrically highly reliable items, which closely reflect overall severity. However, both of these scales have not yet been evaluated in prospective trials. Two shorter versions, the Brief PANSS and the PANSS-6, both include six items, which represent in a balanced fashion the positive and negative domains of schizophrenia. Two of their respective items overlap (Delusions and Social Withdrawal), while other items are quite different between the two scales. The PANSS-6 has been tested quite extensively in established trials and appears to demonstrate high sensitivity to change and an established cutoff definition for remission. Prospective use of PANSS-6 and Brief PANSS in antipsychotic treatment trials is still required for these scales, however. In addition, these scales need to be supplemented with interview guides, as well as provide conversion formulas to translate total scores from the short PANSS versions to the PANSS-30. PANSS-6 and Brief PANSS are essentially designed to evaluate patient response to antipsychotic treatment. Most, if not all, antipsychotic treatments aim at decreasing positive symptoms and have no or significantly lesser effects on negative symptoms. Improvement or score reduction in any rating scale measuring current antipsychotic treatment effects will therefore measure predominantly positive symptoms and, to a much lesser degree, negative symptoms. It might therefore be possible to develop a short PANSS version that focuses predominantly on uniquely treatment- sensitive positive symptoms. On the other hand, explorations of drug effects with novel mechanisms of action might require a fuller PANSS instrument in order to find new and/or additional treatment effects in domains other than positive symptoms. Additionally, investigations of symptom structure and biological correlates of schizophrenia might continue to need the full PANSS in order to investigate the full spectrum of schizophrenia symptoms. The development of a phase- specific version of PANSS should also be

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