Innovations In Clinical Neuroscience

NOV-DEC 2017

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

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27 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 significantly associated with inability to validly complete neurocognitive testing at acute study baseline. Furthermore, significant associations were found across all treatment groups for improvement in insight with cognitive performance (assessed by the CogState composite score), functional capacity (assessed by UPSA-B), depressive symptoms (assessed by MADRS), and quality of well-being (assessed by rater-administered Quality of Well-Being Scale Self-Administered [QWB-SA] scale) over the double-blind, six-week acute study period. Long-term improvement in insight and judgment, as well as schizophrenia symptom severity, was significantly greater for lurasidone 40 to 160mg/d compared to quetiapine XR 200 to 800mg/d assessed over a double-blind, six-month continuation treatment period that followed the six-week, acute treatment study. In the current analysis, significant longitudinal associations between long-term improvement in insight and functional outcomes, as well as reduction in depressive symptoms, were found across treatment groups. These results are consistent with analyses showing significant association between change in insight, medication attitudes, symptoms, and functioning in previous studies, 5,34,40 including our reports that lurasidone 40 to 160mg/d improved cognition from baseline more than quetiapine XR 200 to 800mg/d in the six-month continuation study, independently of treatment related improvement in symptoms. 34,35 These results raise the possibility that lurasidone might enhance everyday functioning (vs. placebo) through a set of related outcomes, including symptom reduction, increased cognitive performance, increased ability to perform tests of functional capacity, and increased awareness of current level of functioning, mediated in part by improvements in insight and judgment. Insight impairment (as assessed by PANSS-item G12 or other multidimensional measures) is a core feature of schizophrenia and other psychotic disorders, and hence an integral part of clinical status. Several published factor analyses have shown that insight regarding illness is not an independent psychopathological factor 41,42 and is closely related to disorganized symptoms. 40–42 The PANSS-item G12 "insight and judgment" is a component of PANSS and contributed to the overall PANSS score. Consistent with previous studies, 5,12,40 the improvement in "insight and judgment" observed with lurasidone and quetiapine XR treatment over the acute and continuation studies in this analysis was not independent of the general change in psychopathology (as assessed by changes in PANSS total score and PANSS positive and negative subscale scores). The causality and directionality of changes in insight and overall improvement in clinical status, however, are not clear. It seems evident that patients lacking insight and awareness of illness might not see the need for treatment, might not attribute symptoms properly to their illness, and might have difficulty assessing the effects of symptoms on subjective measures of quality of life (QoL) and functioning. 8,12,40 A post-hoc analysis of the large-scale CATIE trial found that lack of insight and judgment at pre-treatment baseline moderated the FIGURE 4. Longitudinal relationship between changes in insight and quality of well-being from acute study baseline (mixed effects LDA model): **P<0.01 (regression slope at Week 6), *p<0.05 (regression slope at Week 32). Positive and Negative Syndrome Scale (PANSS)-item G12 -- positive change scores represent improvement from baseline.

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