Innovations In Clinical Neuroscience

NOV-DEC 2017

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

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28 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 relationships among subjective QoL, symptom severity, everyday functioning, and treatment dropout in schizophrenia. 8 These CATIE study findings supported the presence of a subgroup of patients with marked psychiatric symptoms, poor insight, low self-reported depressive symptoms, and impairment in cognitive functioning. Patients in this subgroup were also less cooperative and more likely to discontinue treatment. 8 In our analysis of acute phase baseline data, we identified a similar trend showing that patients with an acute exacerbation of schizophrenia and impairment in insight tended to be uncooperative, have greater impairment in cognition, and perform poorly on objective measures of cognition and functional capacity. This post-hoc analysis represents the first longitudinal study to demonstrate that treatment-related improvement in insight is significantly associated with better performance on objective measures of cognition, functional outcomes, and health-related quality of life and reduction in depressive symptoms in patients with schizophrenia. A recent meta-analysis 12 confirmed that insight "is a potential therapeutic target and that it is amenable to improvement." The meta- analysis also made the striking observation that there were almost no randomized trials of psychosis, except one two-year study, 43 that reported separately the effects of antipsychotics on change in insight. Given that reduced insight has been found to be associated with poor treatment adherence and poor outcomes, 5,12,15,17–20 there is an important need to assess and report insight as a separate, targeted outcome in controlled treatment studies. Limitations. The use of the single PANSS-item G12 for measuring insight and judgment is a limitation of this study. This one-item measure of insight and judgment has, however, demonstrated a robust psychometric relationship with the more global Insight and Treatment Attitudes Questionnaire (ITAQ) measure as assessed in the CATIE trial (Spearman rank correlation r=0.49, p<0.001, N=1232). 8 Sanz et al also reported that PANSS insight and judgment item (G12) had concurrent validity with three other common measures of illness insight in schizophrenia, 25 including ITAQ (r=0.904), 2 Schedule for the Assessment of Insight ([SAI], r=0.884; SAI- expanded version [E], r=0.895), 13 and Berrios and Markova's scale. 28 The validity of PANSS- item G12 for for the assessment of insight and judgment in patients with schizophrenia was supported in this study by the item's significant cross-sectional (at baseline) and longitudinal (both six weeks and six months) associations with objective assessments of cognitive performance, function and quality of well-being outcomes, that were observed in the current analysis. 8 The statistically significant separation from placebo on improvement in PANSS-item G12 score in the treatment groups (lurasidone 80mg/d, lurasidone 160mg/d, and quetiapine XR 600mg/d) in the acute phase, as well as significant separation between LUR-LUR and QXR-QXR at Week 32 in the extension phase, demonstrated the ability of this single PANSS-item G12 to detect score change associated with treatment effect. This analysis presented here confirms the results of previous studies that the single PANSS-item G12 (which has been shown to have robust psychometric relationships with global measures of illness insight in patients with schizophrenia) can detect clinically meaningful score changes associated with treatment effect. It should also be noted that the evaluations of long-term effects of lurasidone and quetiapine XR on change from acute phase baseline (Week 0) in "insight and judgment" and functional outcomes were based on subjects who had completed the six-week acute phase and participated in the six- month, double-blind continuation study. Our findings showed that the demographic and clinical characteristics for randomized subjects were similar between treatment groups and comparable to the completers of the acute phase, suggesting minimal impact of possible selection bias due to dropout over the acute or continuation study phases. In summary, in this post-hoc analysis of a placebo-controlled schizophrenia trial followed by a double-blind, continuation study, patients treated with flexibly dosed lurasidone 40 to 160mg/d demonstrated significant improvement in insight and judgment compared to those treated with quetiapine-XR 200 to 800mg/d at Week 32 (six months) (end of the double-blind, continuation study). In addition, our findings suggest that treatment- related improvement in insight and judgment from acute baseline were associated with better performance on objective measures of cognition, functional outcomes, health-related quality of life, and reduction in depressive symptoms across the treatment groups over the six-week acute phase and a six-month, double- blind continuation treatment period. Further research is warranted to examine the extent to which impaired illness awareness among patients with schizophrenia can be ameliorated by treatment intervention and the effect of improvement in insight on long-term patient outcomes. REFERENCES 1. Amador XF, Strauss DH, Yale SA, et al. Awareness of illness in schizophrenia. Arch Gen Psychiatry. 1994;51:826–836. 2. McEvoy JP, Joy-Apperson L, Appelbaum P, et al. Insight in schizophrenia: its relationship to acute psychopathology. J Nerv Ment Dis. 1989;177:43–47. 3. Schwartz RC. Insight and illness in chronic schizophrenia. Compr Psychiatry. 1998;39:249– 254. 4. Keshavan M, Rabinowitz J, DeSmedt G, et al. Correlates of insight in first episode psychosis. Schizophr Res. 2004;70:187–94. 5. Mohamed S, Rosenheck R, McEvoy J, et al. Cross- sectional and longitudinal relationships between insight and attitudes toward medication and clinical outcomes. Schizophr Bull. 2009;35:336- 346. 6. Harvey PD, Helldin L, Bowie CR, et al. Performance-based measurement of functional disability in schizophrenia, a cross-national study in the United States and Sweden. Am J Psychiatry. 2009;166:821–827 7. Cavelti M, Beck EM, Kvrgic S, et al. The role of subjective illness beliefs and attitude toward recovery within the relationship of insight and depressive symptoms among people with schizophrenia spectrum disorders. J Clin Psychol. 2012;68:462–476. 8. Siu C, Harvey PD, Agid O, et al. Insight and subjective quality of life in chronic schizophrenia. Schizophr Res Cogn. 2015;2:127–132. 9. Kemp R, David A. Insight and compliance. In: Blackwell B (ed.). Treatment Compliance and the Treatment Alliance in Serious Mental Illness. The Netherlands: Harwood Academic;1997:61–86. 10. Olfson M, Marcus SC, Wilk J, et al. Awareness of illness and non-adherence to antipsychotic medications among persons with schizophrenia. Psychiatr Serv. 2006;57:205–211.

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