Pharmacopsychiatry 2023; 56(01): 18-24
DOI: 10.1055/a-1841-6672
Original Paper

Linkage of Young Mania Rating Scale to Clinical Global Impression Scale to Enhance Utility in Clinical Practice and Research Trials

Myrto T. Samara
1   Department of Psychiatry, Faculty of Medicine, University of Thessaly, Larisa, Greece
3   Department of Psychiatry and Psychotherapy, Technical University of Munich, School of Medicine, Munich, Germany
Stephen Z. Levine
2   Department of Community Mental Health, Faculty of Social Welfare and Health Sciences, University of Haifa, Israel
Stefan Leucht
3   Department of Psychiatry and Psychotherapy, Technical University of Munich, School of Medicine, Munich, Germany
› Author Affiliations


Introduction The Young Mania Rating Scale (YMRS) is the gold standard to assess manic symptoms of bipolar disorder, yet the clinical meaning of scores is unknown. To clinically understand and interpret YMRS scores, we examined linkages between the total and change scores of YMRS with the Clinical Global Impression (CGI) ratings.

Methods Individual participant data (N=2,988) from eight randomized, double-blind, placebo-controlled trials were included. Data were collected at baseline and subsequent visits. Spearman’s correlation coefficients ρ were computed, and equipercentile linking was implemented.

Results A YMRS score of 6 points corresponded approximately to ‘borderline mentally ill,’ 12 points to ‘mildly ill,’ 20 points to ‘moderately ill,’ 30 points to ‘markedly ill,’ 40 points to ‘severely ill,’ and 52 points to ‘among the most extremely ill’ patients on the CGI-S. A reduction of CGI-S by one point as well as ‘minimally improved’ on the CGI-I corresponded approximately to an absolute decrease of 4 to 8 YMRS points or a 21% to 29% reduction of YMRS baseline score whereas a reduction of CGI-S by two points and ‘much improved’ on the CGI-I corresponded to an absolute decrease of 10 to 15 points or a 42% to 53% reduction of YMRS baseline score.

Discussion The current study findings offer clinicians meaningful cutoff values to interpret YMRS scores. Moreover, these values contribute to the definition of treatment targets, response, remission, and entry criteria in mania trials.

Supplementary Material

Publication History

Received: 04 March 2022
Received: 04 April 2022

Accepted: 24 April 2022

Article published online:
27 July 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

  • References

  • 1 Young RC, Biggs JT, Ziegler VE. et al. A rating scale for mania: Reliability, validity and sensitivity. Br J Psychiatry 1978; 133: 429-435
  • 2 Frazier TW, Demeter CA, Youngstrom EA. et al. Evaluation and comparison of psychometric instruments for pediatric bipolar spectrum disorders in four age groups. J Child Adolesc Psychopharmacol 2007; 17: 853-866
  • 3 Youngstrom EA, Danielson CK, Findling RL. et al. Factor structure of the Young Mania Rating Scale for use with youths ages 5 to 17 years. J Clin Child Adolesc Psychol 2002; 31: 567-572
  • 4 Carlson GA, Jensen PS, Findling RL. et al. Methodological issues and controversies in clinical trials with child and adolescent patients with bipolar disorder: Report of a consensus conference. J Child Adolesc Psychopharmacol 2003; 13: 13-27
  • 5 Youngstrom EA, Findling RL, Youngstrom JK. et al. Toward an evidence-based assessment of pediatric bipolar disorder. J Clin Child Adolesc Psychol 2005; 34: 433-448
  • 6 Canuso CM, Lindenmayer JP, Kosik-Gonzalez C. et al. A randomized, double-blind, placebo-controlled study of 2 dose ranges of paliperidone extended-release in the treatment of subjects with schizoaffective disorder. J Clin Psychiatry 2010; 71: 587-598
  • 7 Canuso CM, Schooler N, Carothers J. et al. Paliperidone extended-release in schizoaffective disorder: a randomized, controlled study comparing a flexible dose with placebo in patients treated with and without antidepressants and/or mood stabilizers. J Clin Psychopharmacol 2010; 30: 487-495
  • 8 Prisciandaro JJ, Tolliver BK. An item response theory evaluation of the young mania rating scale and the montgomery-asberg depression rating scale in the systematic treatment enhancement program for bipolar disorder (STEP-BD). J Affect Disord 2016; 205: 73-80
  • 9 Furukawa TA. Assessment of mood: Guides for clinicians. J Psychosom Res 2010; 68: 581-589
  • 10 Patel NC, Patrick DM, Youngstrom EA. et al. Response and remission in adolescent mania: signal detection analyses of the young mania rating scale. J Am Acad Child Adolesc Psychiatry 2007; 46: 628-635
  • 11 Tohen M, Jacobs TG, Grundy SL. et al. Efficacy of olanzapine in acute bipolar mania: a double-blind, placebo-controlled study. The Olanzipine HGGW Study Group. Arch Gen Psychiatry 2000; 57: 841-849
  • 12 Lukasiewicz M, Gerard S, Besnard A. et al. Young Mania Rating Scale: How to interpret the numbers? Determination of a severity threshold and of the minimal clinically significant difference in the EMBLEM cohort. Int J Methods Psychiatr Res 2013; 22: 46-58
  • 13 McKnight RF, de La Motte de Broons de Vauvert S, Chesney E. et al. Lithium for acute mania. Cochrane Database Syst Rev 2019; 6: CD004048
  • 14 Earley W, Durgam S, Lu K. et al. Clinically relevant response and remission outcomes in cariprazine-treated patients with bipolar I disorder. J Affect Disord 2018; 226: 239-244
  • 15 Suppes T, Eudicone J, McQuade R. et al. Efficacy and safety of aripiprazole in subpopulations with acute manic or mixed episodes of bipolar I disorder. J Affect Disord 2008; 107: 145-154
  • 16 Tohen M, McIntyre RS, Kanba S. et al. Efficacy of olanzapine in the treatment of bipolar mania with mixed features defined by DSM-5. J Affect Disord 2014; 168: 136-141
  • 17 Biederman J, Mick E, Hammerness P. et al. Open-label, 8-week trial of olanzapine and risperidone for the treatment of bipolar disorder in preschool-age children. Biol Psychiatry 2005; 58: 589-594
  • 18 Frazier JA, Biederman J, Tohen M. et al. A prospective open-label treatment trial of olanzapine monotherapy in children and adolescents with bipolar disorder. J Child Adolesc Psychopharmacol 2001; 11: 239-250
  • 19 Berk M, Ng F, Wang WV. et al. The empirical redefinition of the psychometric criteria for remission in bipolar disorder. J Affect Disord 2008; 106: 153-158
  • 20 Guy W. ECDEU assessment manual for psychopharmacology-Revised. Rockville, Maryland, USA: National Institute of Mental Health; 1976
  • 21 Furukawa TA, Katherine Shear M, Barlow DH. et al. Evidence-based guidelines for interpretation of the Panic Disorder Severity Scale. Depress Anxiety 2009; 26: 922-929
  • 22 Bandelow B, Baldwin DS, Dolberg OT. et al. What is the threshold for symptomatic response and remission for major depressive disorder, panic disorder, social anxiety disorder, and generalized anxiety disorder?. J Clin Psychiatry 2006; 67: 1428-1434
  • 23 Zaider TI, Heimberg RG, Fresco DM. et al. Evaluation of the clinical global impression scale among individuals with social anxiety disorder. Psychological medicine 2003; 33: 611-622
  • 24 Samara M, Levine SZ, Yoshida K. et al. Linking the Clinical Dementia Rating Scale-Sum of Boxes, the Clinician’s Interview-Based Impression Plus caregiver input, and the Clinical Global Impression Scale: Evidence based on individual participant data from five randomized clinical trials of donepezil. J Alzheimers Dis 2021; 82: 1075-1084
  • 25 Bobo WV, Anglero GC, Jenkins G. et al. Validation of the 17-item Hamilton Depression Rating Scale definition of response for adults with major depressive disorder using equipercentile linking to Clinical Global Impression scale ratings: analysis of Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS) data. Hum Psychopharmacol 2016; 31: 185-192
  • 26 Leucht S, Fennema H, Engel RR. et al. What does the MADRS mean? Equipercentile linking with the CGI using a company database of mirtazapine studies. J Affect Disord 2017; 210: 287-293
  • 27 Leucht S, Kane JM, Etschel E. et al. Linking the PANSS, BPRS, and CGI: Clinical implications. Neuropsychopharmacology 2006; 31: 2318-2325
  • 28 Levine SZ, Rabinowitz J, Engel R. et al. Extrapolation between measures of symptom severity and change: An examination of the PANSS and CGI. Schizophr Res 2008; 98: 318-322
  • 29 Samara MT, Engel RR, Millier A. et al. Equipercentile linking of scales measuring functioning and symptoms: Examining the GAF, SOFAS, CGI-S, and PANSS. Eur Neuropsychopharmacol 2014; 24: 1767-1772
  • 30 Post MW. What to do with “Moderate” reliability and validity coefficients?. Arch Phys Med Rehabil 2016; 97: 1051-1052
  • 31 Albano AD. equate: An R package for observed-score linking and equating. J Stat Softw 2016; 74: 1-36
  • 32 Furukawa TA, Levine SZ, Buntrock C. et al. How can we estimate QALYs based on PHQ-9 scores? Equipercentile linking analysis of PHQ-9 and EQ-5D. Evid Based Ment Health 2021; 24: 97-101
  • 33 Levine SZ, Yoshida K, Goldberg Y. et al. Linking the Mini-Mental State Examination, the Alzheimer’s Disease Assessment Scale-Cognitive Subscale and the Severe Impairment Battery: Evidence from individual participant data from five randomised clinical trials of donepezil. Evid Based Ment Health 2021; 24: 56-61
  • 34 R Core Team. R: A language and environment for statistical computing In: Vienna, Austria. R Foundation for Statistical Computing. 2013
  • 35 Berwaerts J, Xu H, Nuamah I. et al. Evaluation of the efficacy and safety of paliperidone extended-release in the treatment of acute mania: A randomized, double-blind, dose-response study. J Affect Disord 2012; 136: e51-e60
  • 36 Vieta E, Nuamah IF, Lim P. et al. A randomized, placebo- and active-controlled study of paliperidone extended release for the treatment of acute manic and mixed episodes of bipolar I disorder. Bipolar Disord 2010; 12: 230-243
  • 37 Haas M, Delbello MP, Pandina G. et al. Risperidone for the treatment of acute mania in children and adolescents with bipolar disorder: A randomized, double-blind, placebo-controlled study. Bipolar Disord 2009; 11: 687-700
  • 38 Kushner SF, Khan A, Lane R. et al. Topiramate monotherapy in the management of acute mania: Results of four double-blind placebo-controlled trials. Bipolar Disord 2006; 8: 15-27
  • 39 Smulevich AB, Khanna S, Eerdekens M. et al. Acute and continuation risperidone monotherapy in bipolar mania: A 3-week placebo-controlled trial followed by a 9-week double-blind trial of risperidone and haloperidol. Eur Neuropsychopharmacol 2005; 15: 75-84
  • 40 Leucht S, Kane JM, Kissling W. et al. What does the PANSS mean?. Schizophr Res 2005; 79: 231-238
  • 41 Hirschfeld RM, Calabrese JR, Frye MA. et al. Defining the clinical course of bipolar disorder: response, remission, relapse, recurrence, and roughening. Psychopharmacol Bull 2007; 40: 7-14
  • 42 Masand PS, Eudicone J, Pikalov A. et al. Criteria for defining symptomatic and sustained remission in bipolar I disorder: A post-hoc analysis of a 26-week aripiprazole study (study CN138-010). Psychopharmacol Bull 2008; 41: 12-23
  • 43 Malmivaara A. Generalizability of findings from randomized controlled trials is limited in the leading general medical journals. J Clin Epidemiol 2019; 107: 36-41
  • 44 Canevelli M, Bruno G, Vanacore N. et al. Are we really tackling the “evidence-based medicine issue” in Alzheimer’s disease?. Eur J Intern Med 2016; 35: e29-e30
  • 45 Beneke M, Rasmus W. “Clinical Global Impressions” (ECDEU): Some critical comments. Pharmacopsychiatry 1992; 25: 171-176
  • 46 Leon AC, Shear MK, Klerman GL. et al. A comparison of symptom determinants of patient and clinician global ratings in patients with panic disorder and depression. J Clin Psychopharmacol 1993; 13: 327-331