Journal of Affective Disorders 150 (2013) 17–22

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Journal of Affective Disorders
journal homepage: www.elsevier.com/locate/jad

Review

Relationship between the clinical global impression of severity
for schizoaffective disorder scale and established mood scales
for mania and depression$
Ibrahim Turkoz a,n, Dong-Jing Fu b, Cynthia A. Bossie b, John J. Sheehan b,c, Larry Alphs b
a

Janssen Research & Development, LLC, 1125 Trenton-Harbourton Road, Titusville, NJ 08650, USA
Janssen Scientific Affairs, LLC, Titusville, NJ, USA
c
Bristol-Myers Squibb, Plainsboro, NJ, USA
b

a r t i c l e i n f o

abstract

Article history:
Received 21 December 2012
Accepted 30 January 2013
Available online 18 March 2013

Background: This analysis explored the relationship between ratings on HAM-D-17 or YMRS and those
on the depressive or manic subscale of CGI-S for schizoaffective disorder (CGI-S-SCA).
Methods: This post hoc analysis used the database (N ¼ 614) from two 6-week, randomized, placebocontrolled studies of paliperidone ER versus placebo in symptomatic subjects with schizoaffective
disorder assessed using HAM-D-17, YMRS, and CGI-S-SCA scales. Parametric and nonparametric
regression models explored the relationships between ratings on YMRS and HAM-D-17 and on
depressive and manic domains of the CGI-S-SCA from baseline to the 6-week end point. A clinically
meaningful improvement was defined as a change of 1 point in the CGI-S-SCA score. No adjustment was
made for multiplicity.
Results: Multiple linear regression models suggested that a 1-point change in the depressive domain
of CGI-S-SCA corresponded to an average 3.6-point (SE ¼0.2) change in HAM-D-17 score. Similarly, a
1-point change in the manic domain of CGI-S-SCA corresponded to an average 5.8-point (SE ¼ 0.2)
change in YMRS score. Results were confirmed using local and cumulative logistic regression models in
addition to equipercentile linking.
Limitations: Lack of subjects scoring over the complete range of possible scores may limit broad
application of the analyses.
Conclusion: Clinically meaningful score changes in depressive and manic domains of CGI-S-SCA
corresponded to approximately 4- and 6-point score changes on HAM-D-17 and YMRS, respectively,
in symptomatic subjects with schizoaffective disorder.
& 2013 Elsevier B.V. All rights reserved.

Keywords:
Schizoaffective disorder
Clinical global impression-severityschizoaffective disorder
Hamilton rating scale-depression,
17-Item version
Young mania rating scale

Contents
1.
2.

3.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
2.1.
Study design. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
2.2.
Statistical analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
3.1.
Subjects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
3.2.
Clinically meaningful changes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
3.2.1.
CGI-S-SCA depressive domain and HAM-D-17 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
3.2.2.
CGI-SCA mania domain and YMRS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
3.3.
Sensitivity analysis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

$
Prior presentation: Parts of these data were previously presented as a poster at the 7th Annual International Society for CNS Clinical Trials and Methodology Scientific
Meeting, February 21–23, 2011, Washington, DC, and the 51st Annual New Clinical Drug Evaluation Unit Meeting, June 13–16, 2011, Boca Raton, FL, USA.
n
Corresponding author. Tel.: þ609 730 7719; fax: þ 609 730 3125.
E-mail address: ITurkoz@its.jnj.com (I. Turkoz).

0165-0327/$ - see front matter & 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jad.2013.01.047

. . . . All raters had clinical and/or research experience with this subject population. . . . YMRS scores of approximately 13. . . . . . . 20 to 25. . . This analysis explored the relationships between ratings on both the HAM-D-17 and the YMRS and those on the depressive and manic domains of the CGI-S-SCA. . A CGI-Improvement (CGI-I) rating of ‘‘minimal improvement’’ was associated with BPRS reductions between 1 and 4 weeks of treatment of 24% to 30%. . as percent reductions. . . . . . . . Change on this scale has strong face validity. . . . 22 References . . The Clinical Global Impression-Severity (CGI-S) scale has been widely used to measure clinical outcomes in symptom severity and treatment efficacy in subjects with psychoses (Guy. . and depressive). placebo-controlled studies of paliperidone ER treatment versus placebo in subjects with schizoaffective disorder (Canuso et al. . .. . . . . . 2003). . . . . . . . . . . . . . . . . . . such interpretation is limited. . Although these data may facilitate approximation of what might be considered a meaningful change score. . . and 6 (end point). . a change of 1 or more points on the CGI-S can be considered clinically meaningful. . Furthermore. . . . . . . . . . . . . . . . HAM-D-17 scores of 0 to 7. Ratings on these scales were based on symptoms during the week before the assessment visit. . . . . . . . Although these scales are used to measure schizoaffective disorder in clinical trial settings. . and CGI-S-SCA (overall score and manic and depressive domains). reported that a reduction in PANSS of approximately 50% corresponded to a ‘‘much improved’’ CGI-I rating (Leucht et al. . . . Assessments for the original studies included the HAM-D-21. . more recently. . Discussion . . . . . . . . . 2012). . . . . . . For example. . . . . moderate. . . . . . . . . . . . . . . . . manic. To focus on the core symptoms of depression. . Whenever possible. . . . . . . . . . . . . . . . . 2001). All subjects had been given a confirmed diagnosis of schizoaffective disorder based on the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders. or mixed episode (American Psychiatric Association. 2010b. Methods 2.. In another study of subjects with schizophrenia. Study design This post hoc analysis used a database (N ¼614) composed of two six-week. . . . . . . . . . . . . 1976). . . . . only the first 17 (HAM-D-17) of the 21 items of the HAM-D-21 scale were used in this post hoc analysis. . . . . 2010b. . . The latter includes ratings of severity of the four schizoaffective disorder domains (positive. .. . For example. . . . . . . . . a correlation was reported between Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression (CGI) ratings in symptomatic subjects with schizophrenia (Leucht et al. severe. . 2010a. . . . . . . . 1997). and. . . . . . . . . from the HAM-D data. . . . . . and poor impulse control]). . . . . . and 26 and higher corresponded to no. / Journal of Affective Disorders 150 (2013) 17–22 4. . . . . . . . . . . . clinically meaningful changes in scale scores on these instruments are not well established. . . . . . and the Hamilton Rating Scale-Depression. as well as for a major depressive. . . . . YMRS and HAM-D. . . . . These were assessed at baseline. . . . . . .1. . . . . . . . . 2010c). . . . 2007). . . the Young Mania Rating Scale (YMRS. . . . . . . . . a 1-point change could shift categories of severity but is unlikely to be considered a clinically relevant change. . . Several other publications have examined relationships between various psychiatric scales with the intent of helping to define clinically meaningful changes. with YMRS and/or HAM-D-21 scores Z16 and PANSS total scores Z60 (plus scores Z4 on Z2 PANSS items [hostility. . . . . . . . . . NCT00397033). . 17. . . . 2010c). . . . . . . 2005a). . for schizoaffective disorder (CGI-S-SCA). . . . . . whereas a rating of ‘‘much improved’’ corresponded to BPRS reductions of 44% to 58% (Leucht et al. . . . . 22 5. . 26. . . . . . . . Leucht et al.. . . . . . . . Disorders (SCID). . . . . . . . . . . . . . . 22 Acknowledgments .. . . among them the CGI for schizophrenia (CGI-SCH) (Haro et al. . . . A meta-analysis of seven trials of major depressive disorder suggests that a 4-point or less reduction in HAM-D-17 score indicated no improvement in symptomatic subjects (Furukawa et al. 2007). . . . . provided these medications had been given at a stable dose within 30 days of screening. for bipolar disorder (CGI-BP) (Spearing et al. . Conclusions . . . . . . In a comparison of acute and longer-term treatment outcomes of the Sequenced Treatment Alternatives to Relieve Depression trial. . . . . day 4. . . . . . . . . . . . . . . . . .. . . . Furukawa et al. . . . . 14 to 19. . . . Published reports describing clinically meaningful changes in CGI-S with the commonly used mood scales. . . . . and severe manic symptom severity levels. . 4. Limitations . . . . . . . .. . . . . . . . . . . . . . . .. . Young et al. . . 2005a). . . . . . 2006). or in relation to a predefined threshold score. . . 1967. . . . Introduction Schizoaffective disorder identifies a clinical entity whose symptoms encompass criteria for schizophrenia. . . . . . . . . . . . plus an overall rating (Allen et al. . . 2010a. . . respectively (Rush et al. . . Vieta et al. . . . . . . . . uncooperativeness. . . . . . . . . . . . . . . . . 21 4. . . . . . . . . . . . . . . . . . negative. . . and had passed required certification for the scales. . . . . . . excitement.. . . . . . . . 2005b). and 38 have been suggested to correspond to minimal. . . and the usefulness of this measurement approach is reflected in the fact that many disorder-specific CGI scales have been introduced into clinical trials. 1978). . Data are often evaluated as change scores. . . . . . . . . . . . had participated in study-specific training. . . . . . . . . . . . . . . . . . . . . . . . . . . 1976). PANSS total. . . . . respectively (Young et al. . . . . . . . . . . . . . . . . . and. . . . . to determine which change score on the mood scales corresponds to a 1-point (i. . . . . . Subjects had an acute exacerbation of schizoaffective disorder. . . . . . . . . moderate. 22 1. . . . . . . . . . . 2. . .and 21-item versions (HAM-D-17 and HAM-D-21) (Hamilton. . . . . . . . . . . . . . Studies of schizoaffective disorder have traditionally used a combination of scales designed to assess schizophrenia or mood disorders. . . . Fourth Edition (DSM-IV-TR). such as the Positive and Negative Syndrome Scale (PANSS). . . . . . . . . . . . . .1. . YMRS. . . This scale has ratings from 1 (not ill) to 7 (extremely ill) (Guy. . . . . . . . . . .. . . . . . . . . . . 22 Conflict of interest. . . . . are limited and have not discussed the schizoaffective population (Kemp et al. .e. . the same raters at each site assessed the same subjects throughout the study. . .18 I.. . . mild. and CGI ratings from 14 drug trials in acutely ill subjects with schizophrenia reported that an absolute reduction in BPRS/PANSS by 10–15 points corresponded to a CGI-I of ‘‘minimally improved’’ and to a change in the CGI-S score of 1 point (Leucht et al. mild. . . and weeks 1. . . . . 2. . 22 Role of funding source . 2006). 3. . . . .. . . clinically meaningful) change on the CGI-S-SCA in subjects with schizoaffective disorder (Canuso et al. . However. . . . . . . . . . . . . . . 8 to 13. . . an equipercentile linking analysis of PANSS. . . .. . . 20. . .. which included similar subject populations and study designs (NCT00412373. Subjects were permitted to receive concomitant treatment with mood stabilizers and/or antidepressants. . . . . . . . manic. . . . . .. . . BPRS. . . . . . 1978). . . . . . . . . such a change is highly dependent on initial scores at baseline. . Turkoz et al. . . . . . . . . . 2006). . . . . . randomized. and very severe depressive symptoms. . . 2011. .. . . empirically. .. . tension. . . . . .

subjects had a mean (standard deviation [SD]) YMRS score of 24.3 59. HAM-D-17: Hamilton Rating Scale-Depression. CGI-S-SCA: Clinical Global Impression-Schizoaffective Disorder.001 0. and 60% were male.. or worsening (severity score increased by one or more units). and severe (38) manic symptoms (Young et al.3 1. Simple and multiple (with explanatory study design variables for treatment.4 6. Nearly half of subjects (45%) were taking mood stabilizers and/or antidepressants.001 0.0 1.001 o 0.2.7 36.1. severe (20 to 25). Equipercentile equating defines a nonlinear relationship between score scales by setting the percentile ranks equal for each point. Sensitivity analysis is an essential element in model building. 2010c).36. the equipercentile equating involved first determining percentile ranks for the relevant domain of CGI-S-SCA and HAM-D-17.589 Least squares estimates of YMRS point change (SE) P value r2 Baseline demographic and clinical characteristics and improvement in efficacy measures from baseline to end point have been reported previously (Canuso et al. At baseline. Probabilities Z20% are highlighted in italic. Subjects Least squares estimates of HAM-D-17 point change (SE) P value r2 4.2 12.. P-valueo 0.8 (8.4 (10.6 (0. 2010b. 2001) was performed to determine the correspondence of CGI-S-SCA depressive domain scores to HAM-D-17 and HAM-D-21 scores.. CGI-S-SCA depressive domain and HAM-D-17 Results from simple and multiple regression models for CGI-SSCA depressive domain and HAM-D-17 are shown in Table 1. Assumptions such as a linear relationship between variables and equal variances of error terms were evaluated using residual plots.2 0 0 0 14. Simple regression Multiple regression moderate (26).5 (1. Clinically meaningful change was defined as a 1-point change in the CGI-S-SCA scale score.9 23.0). Local regression models were conducted to allow greater flexibility than is seen with traditional modeling tools—an approach used in situations in which a suitable parametric form of the regression surface is not known.0). At the study end point.630 0. This approach is also appropriate when outliers are noted in the data and a robust fitting method is necessary.2 Ordinal logistic regression model with HAM-D-17as a predictor (odds ratio: 1. Simple regression Multiple regression 19 Testing the hypothesis that the corresponding least squares estimates are equal to 0. a mean (SD) HAM-D-17 score of 16. Clinically meaningful changes Table 1 HAM-D-17 and YMRS changes associated with a 1-point change in CGI-S-SCA depressive and manic domains from baseline to endpoint. Both YMRS and HAM-D-17 scores were also categorized. YMRS: Young Mania Rating Scale.675 3.2) o 0.5 41.05 indicates that there is strong evidence that the slope is not equal to 0.2 20.2 (1.2) o 0.1 0 0 0 25.2. and of CGI-S-SCA manic domain scores to YMRS scores. 6.2) 3.5). Turkoz et al.1. / Journal of Affective Disorders 150 (2013) 17–22 2. Subjects’ mean age was 37 years.40). moderate (14 to 19). mild (20).516 0.4 0. Predicted probabilities of CGI-S scores were computed for given YMRS and HAM-D cut-off points. 17-item version.9 51.6 (0. Additional logistic regression models were fitted using the change score of CGI-S-SCA as a categorical variable. Results 3.3 0 5.. unchanged (0). 2010c). HAM-D-17: Hamilton Rating Scale-Depression. respectively. Ordinal logistic regression models were used to determine expected values of HAM-D-17 and YMRS at end point for each anchor point in the CGI-S-SCA.7 8. Equipercentile linking analysis (Price et al. and mean (SD) CGI-S depression and manic domain scores of 3.2.7 0 19.. 3.4 (0. concomitant medication strata. protocol. 2006). and very severe ( Z26) depressive symptoms (Rush et al. 2010a. Briefly. the simple regression model suggested that a 1-point change in score for the CGI-S-SCA depressive Table 2 Distribution of HAM-D-17 scores by CGI-S-SCA depressive domain score at week 6 end point.001 o 0. No adjustment was made for multiplicity. The schizoaffective disorder type was bipolar in 69% of subjects and depressive in 31%.2) 5. as continuous dependent variables. Percentiles of the cumulative distribution of observed values for the two scales were mapped by the method of Leucht (Leucht et al. HAM-D-21.5) and 3.3 26. and HAM-D-17 cut-off scores were no (0 to 7).I. Both equipercentile linking analysis and local regression approaches were employed. Additional simple and multiple regression models were used to explore relationships between HAM-D-17 and YMRS and CGI-S-SCA depressive and manic domain scores from baseline to end point by concomitant medication status (with or without antidepressants and/or mood stabilizers). CGI-S-SCA: Clinical Global Impression-Severity-Schizoaffective Disorder. respectively (Canuso et al. 2005b). Regression coefficients and r2 were calculated at each visit in addition to week 6 end point to support the consistency of observed estimates over time. SE: standard error.7 44.7 11. from baseline to the week 6 end point. 17-item version..31 to 1. 95% CI: 1. individual scores on the CGI-S-SCA scale and on the relevant mood scale with equipercentile rank were matched together. mild (8 to 13). Categories of change in CGI-S-SCA were defined as improved (severity score lowered one or more units). Statistical analysis The intent-to-treat population used for this analysis included randomly assigned subjects who received at least one dose of study medication and at least one postbaseline efficacy evaluation. 3. YMRS cut-off values were minimal (13). Second. or YMRS. 1978).9 22. . and baseline score) regression models explored relationships between change scores on the HAM-D-17 and the YMRS and the depressive or the manic domain of the CGI-S-SCA scale. Predictive probability of HAM-D-17 score at end point (%) CGI-S-SCA depressive domain 0–7 n¼ 291 8–13 n ¼150 14–19 n ¼96 20–25 n ¼49 Z26 n ¼27 CGI-S-SCA ¼1 normal CGI-S-SCA ¼2 minimally ill CGI-S-SCA ¼3 mildly ill CGI-S-SCA ¼4 moderately ill CGI-S-SCA ¼5 markedly ill CGI-S-SCA ¼6/7 severely ill/extremely severely ill 62.5 4.8 (0.

48 and 0. The predictive probability of the HAM-D-17 score range for each CGI-S-SCA depressive score is outlined in Table 2. with numerically increasing values observed over time.63. Simple regression model-determined changes in scores for the CGI-S of manic symptoms from baseline to end point were 6. The logistic regression model with the CGI-S-SCA depressive domain categories of change suggested an average 36% probability of a shift of one category at end point when the HAM-D-17 score changed by 1 point.20 I.1 4. CGI-SCA mania domain and YMRS Results from simple and multiple regression models for the CGI-S-SCA mania domain and YMRS are shown in Table 1.2 0 58.7 47. respectively. Turkoz et al.5 32.4-point (standard error [SE] ¼0.45 and 0. The relationship between CGI-S-SCA and YMRS did not differ between subjects taking antidepressants and/or mood stabilizers and subjects receiving paliperidone ER monotherapy.3 21.33).52. 1.8 44.2 and 6.5 0 0 4.2) change in the YMRS. 17-item version (HAM-D-17). 1 and 2 show the equipercentile linking analyses and local regression models conducted between CGI-S-SCA depression and manic domain scores and HAM-D-17 and YMRS scores at each time point.30. YMRS: Young Mania Rating Scale.4 8.8 0. Sensitivity analysis 3.3 41.3 15. The observed r2 ranged between 0. The overall relationship between CGI-S-SCA and HAM-D-17 did not differ between subjects taking antidepressants and/or mood stabilizers compared with those not taking concomitant medications.3. and the highest value observed at week 6. Probabilities Z 20% are highlighted in italic. for subjects with and without concomitant medications.2 0.2) change in the HAM-D-17 score. These results suggest that the relationship between the two variables (CGI-S-SCA depressive domain and HAM-D-17) was consistent at each visit.4 42.2) on the YMRS. and r2 was 0. The regression coefficient from least squares ranged between 3. A simple regression model suggests that a 1-point change in the Figs.6-point (SE ¼0.64. Markedly ill 5 Moderately ill 4 Baseline (N = 614) Day 4 (n = 609) Week 1 (n = 579) Week 2 (n = 508) Week 3 (n = 452) Week 4 (n = 429) Week 6 (n = 392) Mildly ill 3 Minimally ill 2 Normal 1 0 5 10 15 20 25 HAM-D-17 Total Score 30 35 40 0 5 10 15 20 25 30 35 40 HAM-D-17 Total Score Fig.9 6.0 0 0 0 28.55. scores at each time point. 3.5.2.1 33.3 37. The logistic regression model-determined changes in the CGIS-SCA manic domain categories suggested an average 30% probability of a shift of one category at end point when the YMRS score changed by 1 point. The simple regression analysis identified that changes in CGI-S depressive symptoms from baseline to end point for subjects with and without concomitant medications were 4.3 13. whereas a multiple regression model suggested correspondence to an average least square estimate of a 3. and r2 was 0.26 to 1. Predictive probability of YMRS score at end point (%) CGI-S-SCA manic domain 0–7 n ¼202 8–12 n ¼113 13–19 n¼129 20–25 n¼ 74 26–37 n ¼71 Z 38 n¼ 24 CGI-S-SCA ¼1 normal CGI-S-SCA ¼2 minimally ill CGI-S-SCA ¼3 mildly ill CGI-S-SCA ¼4 moderately ill CGI-S-SCA ¼5 markedly ill CGI-S-SCA ¼6/7 severely ill/extremely severely ill 73.8 points (SE¼0. Equipercentile linking (A) and local regression model (B) results between Clinical Global Impression-Severity-Schizoaffective Disorder (CGI-S-SCA) depression domain and Hamilton Rating Scale-Depression.3 21.61 and 0. The observed r2 ranged from 0. Predictive probabilities of changes in the YMRS score for each CGI-S-SCA manic score are outlined in Table 3.6 23. with numerically increasing values observed over time. an Table 3 Distribution of YMRS scores by CGI-S-SCA manic domain score at week 6 end point.8 5. For reference and sensitivity purposes.0 and 6. and the highest value observed at week 6.2 0 0 16.9 and 4. CGI-S-SCA: Clinical Global Impression-Severity-Schizoaffective Disorder. respectively. These results suggest that the relationship between the two variables (CGI-S-SCA manic domain and YMRS) was consistent at each visit starting from week 1.2.5 Extremely ill 7 Extremely ill 7 Severely ill 6 Severely ill 6 Markedly ill 5 Moderately ill 4 Baseline (N = 614) Day 4 (n = 609) Week 1 (n = 579) Week 2 (n = 508) Week 3 (n = 452) Week 4 (n = 429) Week 6 (n = 392) Mildly ill 3 Minimally ill 2 Normal 1 CGI-S-SCA Depressive Domain Score CGI-S-SCA Depressive Domain Score Ordinal logistic regression model with YMRS as a predictor (odds ratio: 1. domain corresponded to an average least squares estimate of a 4.6 units. / Journal of Affective Disorders 150 (2013) 17–22 CGI-S-SCA mania domain corresponds to a least squares estimate of a 6.6-point (SE¼0. .45 to 0. The multiple regression model identified this change to be 5.8. 95% CI: 1.2) change in the HAM-D-17 score.3 and 4.4 units based on simple regression analysis.6 9. The regression coefficient ranged between 5.5 0 0 1.8 8.

and r2 increased over time and was highest at week 6. Several different analyses were employed in this work so as to provide multiple lines of evidence from different approaches to support the results. respectively. offering investigators a unique opportunity to identify clinically meaningful changes. The large population used in this study had diverse baseline and end point scores. 2. Correlation among the scales appears to be independent of time. HAM-D-21. being considered ‘‘moderately ill’’ (CGI-S¼ 4) in the depression domain corresponded to a score of approximately 17 on HAM-D-17 at the week 6 end point. 21-item version (HAM-D-21). additional analysis was conducted between the CGI-S-SCA depression domain and the HAM-D-21 scores at each time point (Fig. This was identified by correlating changes in ratings on the HAM-D-17 or YMRS with those on the depressive and manic domains of the CGI-S-SCA. 2007). 4. Results suggest that clinically meaningful changes (1-point change in severity) in depressive and manic domains of the CGI-SSCA score corresponded to approximately 4. 3). Ordinal logistic regression models were used to determine expected values for HAM-D-17 and YMRS scores at end point for each anchor point in the CGI-S-SCA. Turkoz et al. respectively. the overall relationship between the scales did not appear to change.. Simple and multiple regression models suggest that the overall relationship between CGI-S-SCA and mood scales is not dependent on whether subjects are receiving concomitant stable doses of antidepressants and/or mood stabilizers. Similarly. Equipercentile linking (A) and local regression model (B) results between Clinical Global Impression-Severity-Schizoaffective Disorder (CGI-S-SCA) manic domain and Young Mania Rating Scale (YMRS) scores at each time point. although treatment can differentially affect the various symptom domains of schizoaffective disorder. These analyses assist in interpretation of published data using different scales and in identification of selection criteria for clinical trials. Results suggested that being considered ‘‘mildly ill’’ (CGI-S¼3) in the depression domain corresponded approximately to a HAM-D-17 score of 12 at the week 6 end point. the psychometric properties of these scales appear to remain constant. Linking analyses and local regression models were performed to further examine the association between CGI-S-SCA depressive and manic domain scores and HAM-D-17 and YMRS scores. Linking analysis and local regression models suggest that the relationship between the CGI-S-SCA depressive score and the HAM-D-17 score follows a linear trend over the 6-week study period. The relationship between CGI-S-SCA depressive and manic domain scores and HAM-D-17. CGI-S-GCA Depressive Domain Score Extremely ill 7 Severely ill 6 Markedly ill 5 Moderately ill 4 Baseline (N = 614) Day 4 (n = 609) Week 1 (n = 579) Week 2 (n = 508) Week 3 (n = 452) Week 4 (n = 429) Week 6 (n = 392) Mildly ill 3 Minimally ill 2 Normal 1 0 5 10 15 20 25 30 35 40 45 HAM-D-21 Total Score Fig. Simple and multiple regression models were used to examine relationships between change scores on the HAM-D-17 and the YMRS and on the corresponding depressive or manic domains of the CGI-S-SCA. Being considered ‘‘moderately ill’’ (CGI-S¼4) in the manic domain corresponded to a score of approximately 24 on YMRS at the week 6 end point.and 6-point absolute changes in HAM-D-17 and YMRS scores. Discussion The aim of these analyses was to identify a clinically meaningful change in mood symptoms of subjects with schizoaffective disorder as measured by the HAM-D-17 and the YMRS in symptomatic subjects with schizoaffective disorder. and YMRS scores followed a linear trend. A similar relationship was observed between the CGI-SSCA manic score and the YMRS score. Additional simple and multiple regression models were used to explore the robustness of these relationships in subpopulations with different concomitant medication status. which indicated that a r4-point reduction in HAM-D-17 constituted no meaningful improvement in subjects (Furukawa et al.Extremely ill 7 Extremely ill 7 Severely ill 6 Severely ill 6 Markedly ill 5 Moderately ill 4 Baseline (N = 614) Day 4 (n = 609) Week 1 (n = 579) Week 2 (n = 508) Week 3 (n = 452) Week 4 (n = 429) Week 6 (n = 392) Mildly ill 3 Minimally ill 2 CGI-S-SCA Manic Domain Score CGI-S-SCA Manic Domain Score I. / Journal of Affective Disorders 150 (2013) 17–22 21 Markedly ill 5 Moderately ill 4 Baseline (N = 614) Day 4 (n = 609) Week 1 (n = 579) Week 2 (n = 508) Week 3 (n = 452) Week 4 (n = 429) Week 6 (n = 392) Mildly ill 3 Minimally ill 2 Normal 1 Normal 1 0 5 10 15 20 25 30 35 40 45 50 YMRS Total Score 0 5 10 15 20 25 30 35 40 45 50 YMRS Total Score Fig. Thus. Being considered ‘‘mildly ill’’ (CGI-S¼3) in the manic domain corresponded to a YMRS score of approximately 16 at the week 6 end point. It is possible that untested variables may have influenced the outcomes of the regression models. These results are similar to those reported from a study of subjects with major depression. The relationship between . although subjects’ symptoms improved over the course of the study. Equipercentile linking results between Clinical Global Impression-SeveritySchizoaffective Disorder (CGI-S-SCA) depression domain and Hamilton Rating Scale-Depression. scores at each time point. 3. regardless of concomitant medication.

M. Canuso.. W.G. HAM-D-17 changes of 1 point in some cases correspond to a change in the level of severity.M.. Sheehan was an employee of Janssen Scientific Affairs. C.. Turkoz. LLC. Risperidone safety and efficacy in the treatment of bipolar and schizoaffective disorders: results from a 6-month.. J. Carothers. Rodriguez. in this study. J. USA.A.M. LLC.. J...J.. Modification of the Clinical Global Impressions (CGI) scale for use in bipolar illness (BP): the CGI-BP. D.. Limitations When interpreting these results. References Allen. Diagnostic and Statistical Manual of Mental Disorders. 2012. In contrast. 278–296. Sackeim. the CGI-S manic domain specifically addresses only manic symptoms. correlations between the CGI-S manic domain score and the YMRS score may not be consistent in subjects with hallucinations or delusions. and severe (38) manic symptom severity levels (Young et al. J.. C. It is important to note that these results are based on mean data within a clinical study population.. S. whereas moderately ill subjects in the depressive domain (CGI-S¼4) had mean HAM-D-17 scores of approximately 17. J. 487–495. A. 4. Although these are useful suggestions.. C.... For example.. J...A. W.. BPRS. Journal of Clinical Psychiatry 62. and very severe ( Z26) depressive symptoms (Rush et al.J. Turkoz. Martinez-Aran. T. few subjects had an ‘‘extremely ill’’ CGI-S-SCA score or showed extreme improvement on CGI-S-SCA.. A.. and the decision to submit this paper for publication. Price. Wilkins. Martinez. Applied Psychological Measurement 25. Akechi. D. placebo-controlled study of 2 dose ranges of paliperidone extended-release in the treatment of subjects with schizoaffective disorder. Haro. M... open study.F. A linear correlation was noted over time between CGI-S-SCA depressive scores and HAM-D-17 scores. validity and sensitivity. J. Biggs. G. multicenter.. Okuyama. J.. Computer program exchange: EQUIPERCENT: a SAS program for calculating equivalent scores using the equipercentile method. J. Neuropsychiatric Diseases and Treatment 6. P. Role of funding source Funding for this study was provided by Janssen Scientific Affairs... and are Johnson & Johnson stockholders. M.. E. controlled study comparing a flexible dose with placebo in patients treated with and without antidepressants and/or mood stabilizers.. 2006. Lebowitz.. Leverich. W. D. Kissling. E. 818–825. K. K.. R. and results may differ among schizoaffective subpopulations not represented in this sample...A. Johnson.R. S.. R.. Hamann. C.. Ph. As a result. H.. Ph. Turkoz et al. USA.. Canuso.. Journal of Clinical Psychiatry 71... R. R. for providing writing and editorial assistance. Bartko. All authors were directly involved in the design of the analysis: the collection.S. 2005b. C... 2006. J.. A randomized. Jones. Lurie. pp.. S. E. and of HAM-D-17 scores for no (0 to 7). LLC). Tohen. Acknowledgments The authors wish to acknowledge Matthew Grzywacz.22 I.. 2010b.W. F. analysis. and Sheena Hunt. D. Corbella. M. J. Ishak. active psychotic symptoms may confound assessment of mood symptoms as a certain item of the scale (specifically. T.. Conflict of interest I. item 8. Fu.. 1236–1241. Acta Psychiatrica Scandinavica Supplement. Canuso.R. Kissling. Kosik-Gonzalez.. A. Kemp. Novick.E. In this analysis. Kissling. LLC. S. from ApotheCom (supported by Janssen Scientific Affairs. A. 2001. P. 332. Lindenmayer..A.. K. M. Tables 2 and 3 show that although most subjects may show correlation on the different mood scales. M.M. and also between CGIS-SCA manic scores and YMRS scores. Engel. they are limited in that some YMRS scores are not represented at all. Leucht. 1978).. 2003. P. Etschel.. Hamilton. moderately ill subjects in the manic domain of schizoaffective disorder (CGIS¼4) had mean scores of approximately 24 on the YMRS..M.. J. J. Lavori.P. Turkoz is an employee of Janssen Research & Development. 366–371. Brandt. Guy. 2010c.R. and.R. D. Kosik-Gonzalez.. Rosenbaum. ECDEU Assessment Manual for Psychopharmacology (028 Clinical Global Impressions [CGI]). Canuso. Engel. NJ.. D.. D. W. D. N. Bossie. severe (20 to 25). 15–24. . Alonso.. J.M.. A.R.B. A. M. this will not be the case for every individual subject.J.. which evaluates ‘‘content’’) is largely dependent on hallucinations or delusional symptoms. C. J. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STARnD report. American Psychiatric Association.J.. G. I..C. Turkoz. Furukawa. Journal of Clinical Psychiatry 72. the writing of the report. Fernandez. Alphs are employees of Janssen Scientific Affairs. NJ.V. Niederehe. Development and psychometric evaluation of a clinical global impression for schizoaffective disorder scale. Warden. Role of paliperidone extendedrelease in treatment of schizoaffective disorder. J. 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Fu..D. it is important to remember that the starting population had specific symptomatic inclusion criteria. Fu. Conclusions These post hoc findings suggest that clinically meaningful changes in scores on the depressive and manic domains of the CGI-S-SCA corresponded to approximately 4.. Stewart..J.. Colom.. A. 587–598.. Psychiatry Research 73. Daniel.K. Reinares. C.. Fargas..E..D. 1976. In particular. Alphs.A.J. in keeping with this approach. Journal of Clinical Psychopharmacology 27. a subject with acute psychosis may have an inflated YMRS score that does not truly represent manic symptoms. D. 1997. Walling... Gregor. T.H.. 159–171... What does the PANSS mean? Schizophrenia Research 79.. 2005a. Clinical utility of early improvement to predict response or remission in acute mania: focus on olanzapine and risperidone.. 1905–1917..A. LLC. 2010a. V.. G. Ziegler. Young. 231–238. C. W. 2007. Torrent.D...T. 5. Linking the PANSS. respectively.. D.W. American Journal of Psychiatry 163. E. Arlington. N... having insufficient subjects for these score ranges may have limited the linearity assumption. and is a Johnson & Johnson stockholder. C. Wang. Neuropsychopharmacology 31.. I. M. L... Mavreas. 2011... Meyer. W. Kharbeng.J. Vieta. findings may differ in subjects with other mood disorder diagnoses and in populations with a broader or different distribution of symptom change scores.. Post.. E.R... Lavrentzou. Innovations in Clinical Neuroscience 9. H. 16–23.M. M. N. 1978. J. with increasing correlation coefficients over time. Although the linearity of the relationship between dependent and independent variables was examined using various graphic techniques. Revicki.. Spearing. Luther. I.. moderate (14 to 19).M.-J. C.M.. Araya. VA. Etschel. McGrath. Ochoa... Therefore. J. Schooler. Kane. Nolen. Leucht. S.M... Benabarre. for the YMRS scale.E... E. and interpretation of data.