Background: In a study aimed at identifying the items carrying information regarding the global severity of depression, the 6-item Hamilton Depression Rating Scale (HAM-D6) was derived from the original 17-item version of the scale (HAM-D17). Since then, the HAM-D6 has been used in a wide range of clinical studies. We now provide a systematic review of the clinimetric properties of HAM-D6 in comparison with those of HAM-D17 and the Montgomery Asberg Depression Rating Scale (MADRS). Methods: We conducted a systematic search of the literature in PubMed, PsycInfo, and EMBASE databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Studies reporting data on the clinimetric validity of the HAM-D6 and either the HAM-D17 or MADRS in non-psychotic unipolar or bipolar depression were included in the synthesis. Results: The search identified 681 unique records, of which 51 articles met the inclusion criteria. According to the published literature, HAM-D6 has proven to be superior to both HAM-D17 and MADRS in terms of scalability (each item contains unique information regarding syndrome severity), transferability (scalability is constant over time and irrespective of sex, age, and depressive subtypes), and responsiveness (sensitivity to change in severity during treatment). Conclusions: According to the published literature, the clinimetric properties of HAM-D6 are superior to those of both the HAM-D17 and MADRS. Since the validity of HAM-D6 has been demonstrated in both research and clinical practice, using the scale more consistently would facilitate translation of results from one setting to the other.

Keywords:
Clinimetrics, Antidepressant medication, 6-Item Hamilton Depression Rating Scale, Systematic literature review, Depression rating scale
1.
Feinstein AR: T. Duckett Jones Memorial Lecture. The Jones criteria and the challenges of clinimetrics. Circulation 1982;66:1-5.
2.
Feinstein AR: Clinimetrics. New Haven, Yale University Press, 1987.
3.
Feinstein AR: Clinical biostatistics. XII. On exorcising the ghost of Gauss and the curse of Kelvin. Clin Pharmacol Ther 1971;12:1003-1016.
4.
Hamilton M: A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23:56-62.
5.
Hamilton M: Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol 1967;6:278-296.
6.
Kendall MG: Factor analysis as a statistical technique. J R Stat Soc Series B 1950;12:60-73.
7.
Rasch G: Probabilistic Models for Some Intelligence and Attainment Tests. Copenhagen, Danish Institute for Educational Research, 1960.
8.
Tomba E, Bech P: Clinimetrics and clinical psychometrics: macro- and micro-analysis. Psychother Psychosom 2012;81:333-343.
9.
Bech P: Clinimetric dilemmas in outcome scales for mental disorders. Psychother Psychosom 2016;85:323-326.
10.
Bech P, Gram LF, Dein E, Jacobsen O, Vitger J, Bolwig TG: Quantitative rating of depressive states. Acta Psychiatr Scand 1975;51:161-170.
11.
Bech P, Allerup P, Gram LF, Reisby N, Rosenberg R, Jacobsen O, Nagy A: The Hamilton depression scale. Evaluation of objectivity using logistic models. Acta Psychiatr Scand 1981;63:290-299.
12.
Montgomery SA, Asberg M: A new depression scale designed to be sensitive to change. Br J Psychiatry 1979;134:382-389.
13.
Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group: Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009;339:b2535.
14.
Bech P: The responsiveness of the different versions of the Hamilton Depression Scale. World Psychiatry 2015;14:309-310.
15.
Khan A, Bhat A, Kolts R, Thase ME, Brown W: Why has the antidepressant-placebo difference in antidepressant clinical trials diminished over the past three decades? CNS Neurosci Ther 2010;16:217-226.
16.
Hieronymus F, Emilsson JF, Nilsson S, Eriksson E: Consistent superiority of selective serotonin reuptake inhibitors over placebo in reducing depressed mood in patients with major depression. Mol Psychiatry 2016;21:523-530.
17.
Bech P, Cialdella P, Haugh MC, Birkett MA, Hours A, Boissel JP, Tollefson GD: Meta-analysis of randomised controlled trials of fluoxetine v. placebo and tricyclic antidepressants in the short-term treatment of major depression. Br J Psychiatry 2000;176:421-428.
18.
Licht RW, Qvitzau S, Allerup P, Bech P: Validation of the Bech-Rafaelsen Melancholia Scale and the Hamilton Depression Scale in patients with major depression; is the total score a valid measure of illness severity? Acta Psychiatr Scand 2005;111:144-149.
19.
Guy W: The Clinical Global Impression Scale; in Guy W (ed): ECDEU Assessment Manual for Psychopharmacology-Revised. Rockville, US Department of Health, Education, and Welfare, 1976, pp 218-222.
20.
Ruhe HG, Dekker JJ, Peen J, Holman R, de Jonghe F: Clinical use of the Hamilton Depression Rating Scale: is increased efficiency possible? A post hoc comparison of Hamilton Depression Rating Scale, Maier and Bech subscales, Clinical Global Impression, and Symptom Checklist-90 scores. Compr Psychiatry 2005;46:417-427.
21.
Kyle PR, Lemming OM, Timmerby N, Sondergaard S, Andreasson K, Bech P: The validity of the different versions of the Hamilton Depression Scale in separating remission rates of placebo and antidepressants in clinical trials of major depression. J Clin Psychopharmacol 2016;35:453-456.
22.
Bobo WV, Anglero GC, Jenkins G, Hall-Flavin DK, Weinshilboum R, Biernacka JM: 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.
23.
Bobes J, Bulbena A, Luque A, Dal-Re R, Ballesteros J, Ibarra N, Bech P: The sufficiency of the HAM-D6 as an outcome instrument in the acute therapy of antidepressants in the outpatient setting. Int J Psychiatry Clin Pract 2007;11:146-150.
24.
Holmskov J, Licht RW, Andersen K, Stage TB, Nilsson FM, Stage KB, Valentin JB, Bech PB: Diagnostic conversion to bipolar disorder in unipolar depressed patients participating in trials of antidepressants. Eur Psychiatry 2017;40:76-81.
25.
Paroxetine: a selective serotonin reuptake inhibitor showing better tolerance, but weaker antidepressant effect than clomipramine in a controlled multicenter study. Danish University Antidepressant Group. J Affect Disord 1990;18:289-299.
26.
Martiny K, Refsgaard E, Lund V, Lunde M, Sorensen L, Thougaard B, Lindberg L, Bech P: The day-to-day acute effect of wake therapy in patients with major depression using the HAM-D6 as primary outcome measure: results from a randomised controlled trial. PLoS One 2013;8:e67264.
27.
Chouinard G, Saxena BM, Nair NP, Kutcher SP, Bakish D, Bradwejn J, Kennedy SH, Sharma V, Remick RA, Kukha-Mohamad SA, et al: A Canadian multicentre placebo-controlled study of a fixed dose of brofaromine, a reversible selective MAO-A inhibitor, in the treatment of major depression. J Affect Disord 1994;32:105-114.
28.
Fabre LF, Abuzzahab FS, Amin M, Claghorn JL, Mendels J, Petrie WM, Dube S, Small JG: Sertraline safety and efficacy in major depression: a double-blind fixed-dose comparison with placebo. Biol Psychiatry 1995;38:592-602.
29.
Feiger AD, Heiser JF, Shrivastava RK, Weiss KJ, Smith WT, Sitsen JM, Gibertini M: Gepirone extended-release: new evidence for efficacy in the treatment of major depressive disorder. J Clin Psychiatry 2003;64:243-249.
30.
Rickels K, Chung HR, Csanalosi IB, Hurowitz AM, London J, Wiseman K, Kaplan M, Amsterdam JD: Alprazolam, diazepam, imipramine, and placebo in outpatients with major depression. Arch Gen Psychiatry 1987;44:862-866.
31.
Schneider LS, Nelson JC, Clary CM, Newhouse P, Krishnan KR, Shiovitz T, Weihs K; Sertraline Elderly Depression Study Group: An 8-week multicenter, parallel-group, double-blind, placebo-controlled study of sertraline in elderly outpatients with major depression. Am J Psychiatry 2003;160:1277-1285.
32.
Feiger AD: A double-blind comparison of gepirone extended release, imipramine, and placebo in the treatment of outpatient major depression. Psychopharmacol Bull 1996;32:659-665.
33.
Wilcox CS, Ferguson JM, Dale JL, Heiser JF: A double-blind trial of low- and high-dose ranges of gepirone-ER compared with placebo in the treatment of depressed outpatients. Psychopharmacol Bull 1996;32:335-342.
34.
Lecrubier Y, Clerc G, Didi R, Kieser M: Efficacy of St. John's wort extract WS 5570 in major depression: a double-blind, placebo-controlled trial. Am J Psychiatry 2002;159:1361-1366.
35.
Liebowitz MR, Manley AL, Padmanabhan SK, Ganguly R, Tummala R, Tourian KA: Efficacy, safety, and tolerability of desvenlafaxine 50 mg/day and 100 mg/day in outpatients with major depressive disorder. Curr Med Res Opin 2008;24:1877-1890.
36.
Liebowitz MR, Yeung PP, Entsuah R: A randomized, double-blind, placebo-controlled trial of desvenlafaxine succinate in adult outpatients with major depressive disorder. J Clin Psychiatry 2007;68:1663-1672.
37.
Helmreich I, Wagner S, Mergl R, Allgaier AK, Hautzinger M, Henkel V, Hegerl U, Tadic A: Sensitivity to changes during antidepressant treatment: A comparison of unidimensional subscales of the Inventory of Depressive Symptomatology (IDS-C) and the Hamilton Depression Rating Scale (HAMD) in patients with mild major, minor or subsyndromal depression. Eur Arch Psychiatry Clin Neurosci 2012;262:291-304.
38.
Martiny K, Lunde M, Unden M, Dam H, Bech P: Adjunctive bright light in non-seasonal major depression: results from clinician-rated depression scales. Acta Psychiatr Scand 2005;112:117-125.
39.
Ostergaard SD, Bech P, Miskowiak KW: Fewer study participants needed to demonstrate superior antidepressant efficacy when using the Hamilton melancholia subscale (HAM-D6) as outcome measure. J Affect Disord 2016;190:842-845.
40.
Thase ME, Clayton AH, Haight BR, Thompson AH, Modell JG, Johnston JA: A double-blind comparison between bupropion XL and venlafaxine XR: sexual functioning, antidepressant efficacy, and tolerability. J Clin Psychopharmacol 2006;26:482-488.
41.
Moller HJ, Glaser K, Leverkus F, Gobel C: Double-blind, multicenter comparative study of sertraline versus amitriptyline in outpatients with major depression. Pharmacopsychiatry 2000;33:206-212.
42.
Feiger AD, Rickels K, Rynn MA, Zimbroff DL, Robinson DS: Selegiline transdermal system for the treatment of major depressive disorder: an 8-week, double-blind, placebo-controlled, flexible-dose titration trial. J Clin Psychiatry 2006;67:1354-1361.
43.
Bech P, Fava M, Trivedi MH, Wisniewski SR, Rush AJ: Outcomes on the pharmacopsychometric triangle in bupropion-SR vs. buspirone augmentation of citalopram in the STAR*D trial. Acta Psychiatr Scand 2012;125:342-348.
44.
Sondergaard MP, Jarden JO, Martiny K, Andersen G, Bech P: Dose response to adjunctive light therapy in citalopram-treated patients with post-stroke depression. A randomised, double-blind pilot study. Psychother Psychosom 2006;75:244-248.
45.
Ratti E, Bellew K, Bettica P, Bryson H, Zamuner S, Archer G, Squassante L, Bye A, Trist D, Krishnan KR, Fernandes S: Results from 2 randomized, double-blind, placebo-controlled studies of the novel NK1 receptor antagonist casopitant in patients with major depressive disorder. J Clin Psychopharmacol 2011;31:727-733.
46.
Rasmussen A, Lunde M, Poulsen DL, Sorensen K, Qvitzau S, Bech P: A double-blind, placebo-controlled study of sertraline in the prevention of depression in stroke patients. Psychosomatics 2003;44:216-221.
47.
Bech P: Clinical Psychometrics. Oxford, Wiley Blackwell, 2012.
48.
Ostergaard SD, Bech P, Trivedi MH, Wisniewski SR, Rush AJ, Fava M: Brief, unidimensional melancholia rating scales are highly sensitive to the effect of citalopram and may have biological validity: implications for the research domain criteria (RDoC). J Affect Disord 2014;163:18-24.
49.
Thase ME, Ninan PT, Musgnung JJ, Trivedi MH: Remission with venlafaxine extended release or selective serotonin reuptake inhibitors in depressed patients: a randomized, open-label study. Prim Care Companion CNS Disord 2011;13:pii:PCC.10m00979.
50.
Martiny K, Lunde M, Simonsen C, Clemmensen L, Poulsen DL, Solstad K, Bech P: Relapse prevention by citalopram in SAD patients responding to 1 week of light therapy. A placebo-controlled study. Acta Psychiatr Scand 2004;109:230-234.
51.
Preskorn S, Macaluso M, Mehra DO, Zammit G, Moskal JR, Burch RM; GLYX-13 Clinical Study Group: Randomized proof of concept trial of GLYX-13, an N-methyl-D-aspartate receptor glycine site partial agonist, in major depressive disorder nonresponsive to a previous antidepressant agent. J Psychiatr Pract 2015;21:140-149.
52.
Sheehan DV, Rozova A, Gossen ER, Gibertini M: The efficacy and tolerability of once-daily controlled-release trazodone for depressed mood, anxiety, insomnia, and suicidality in major depressive disorder. Psychopharmacol Bull 2009;42:5-22.
53.
Carmody TJ, Rush AJ, Bernstein I, Warden D, Brannan S, Burnham D, Woo A, Trivedi MH: The Montgomery Asberg and the Hamilton ratings of depression: a comparison of measures. Eur Neuropsychopharmacol 2006;16:601-611.
54.
Bech P, Allerup P, Larsen ER, Csillag C, Licht RW: The Hamilton Depression Scale (HAM-D) and the Montgomery-Asberg Depression Scale (MADRS). A psychometric re-analysis of the European genome-based therapeutic drugs for depression study using Rasch analysis. Psychiatry Res 2014;217:226-232.
55.
Andrich D, Sheridan BE, Luo G: RUMM2030, version 5.1. Perth, RUMM Laboratory Pty Ltd, 2010.
56.
van Moffaert M, de Wilde J, Vereecken A, Dierick M, Evrard JL, Wilmotte J, Mendlewicz J: Mirtazapine is more effective than trazodone: a double-blind controlled study in hospitalized patients with major depression. Int Clin Psychopharmacol 1995;10:3-9.
57.
Hooper CL, Bakish D: An examination of the sensitivity of the six-item Hamilton Rating Scale for Depression in a sample of patients suffering from major depressive disorder. J Psychiatry Neurosci 2000;25:178-184.
58.
Adler M, Hetta J, Isacsson G, Brodin U: An item response theory evaluation of three depression assessment instruments in a clinical sample. BMC Med Res Methodol 2012;12:84.
59.
Hays RD, Hadorn D: Responsiveness to change: an aspect of validity, not a separate dimension. Qual Life Res 1992;1:73-75.
60.
Bech P, Allerup P, Larsen ER, Csillag C, Licht RW: The Hamilton Depression Scale (HAM-D) and the Montgomery-Asberg Depression Scale (MADRS). A psychometric re-analysis of the European Genome-Based Therapeutic Drugs for Depression Study using Rasch analysis. Psychiatry Res 2014;217:226-232.
61.
Feighner JP, Robins E, Guze SB, Woodruff RA Jr, Winokur G, Munoz R: Diagnostic criteria for use in psychiatric research. Arch Gen Psychiatry 1972;26:57-63.
62.
Bech P: Measurement-Based Care in Mental Disorders. New York, Springer, 2016.
63.
Fried EI, van Borkulo CD, Epskamp S, Schoevers RA, Tuerlinckx F, Borsboom D: Measuring depression over time... Or not? Lack of unidimensionality and longitudinal measurement invariance in four common rating scales of depression. Psychol Assess 2016;28:1354-1367.
64.
Kramer PD: Ordinarily Well. The Case for Antidepressants. New York, Farrar, Straus and Giroux, 2016.
65.
Carvalho AF, Sharma MS, Brunoni AR, Vieta E, Fava GA: The safety, tolerability and risks associated with the use of newer generation antidepressant drugs: a critical review of the literature. Psychother Psychosom 2016;85:270-288.
66.
Embretson SE: Implications of a multidimensional latent trait model for measuring change; in Collins LM, Horn J (eds): Best Methods for the Analysis of Change. Washington, American Psychological Association, 1991, pp 184-203.
67.
Lipman RS: Depression scales derived from the Hopkins Symptom Checklist; in Sartorius N, Ban T (eds): Assessment of Depression. Berlin, Springer, 1986, pp 232-248.
68.
Papakostas GI, Ostergaard SD, Iovieno N: The nature of placebo response in clinical studies of major depressive disorder. J Clin Psychiatry 2015;76:456-466.
69.
Bech P: Is the antidepressive effect of second-generation antidepressants a myth? Psychol Med 2010;40:181-186.
70.
Licht RW, Qvitzau S, Allerup P, Bech P: Validation of the Bech-Rafaelsen Melancholia Scale and the Hamilton Depression Scale in patients with major depression; is the total score a valid measure of illness severity? Acta Psychiatr Scand 2005;111:144-149.
71.
Bech P, Ban TA: A short historical review of SCNP with special reference to the UKU. Acta Neuropsychiatr 2014;26:4-7.
72.
Bagby RM, Ryder AG, Schuller DR, Marshall MB: The Hamilton Depression Rating Scale: has the gold standard become a lead weight? Am J Psychiatry 2004;161:2163-2177.
73.
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.
74.
Ostergaard SD, Meyers BS, Flint AJ, Mulsant BH, Whyte EM, Ulbricht CM, Bech P, Rothschild AJ; STOP-PD Study Group: Measuring psychotic depression. Acta Psychiatr Scand 2014;129:211-220.
75.
Ostergaard SD, Pedersen CH, Uggerby P, Munk-Jorgensen P, Rothschild AJ, Larsen JI, Gotzsche C, Sondergaard MG, Bille AG, Bolwig TG, Larsen JK, Bech P: Clinical and psychometric validation of the Psychotic Depression Assessment Scale. J Affect Disord 2015;173:261-268.
76.
Ostergaard SD, Rothschild AJ, Flint AJ, Mulsant BH, Whyte EM, Leadholm AK, Bech P, Meyers BS: Rating scales measuring the severity of psychotic depression. Acta Psychiatr Scand 2015;132:335-344.
77.
Overall JE, Gorham DR: The brief psychiatric rating scale. Psychol Rep 1962;10:799-812.
78.
Ostergaard SD, Rothschild AJ, Flint AJ, Mulsant BH, Whyte EM, Vermeulen T, Bech P, Meyers BS: Establishing the cut-off score for remission and severity-ranges on the Psychotic Depression Assessment Scale (PDAS). J Affect Disord 2016;190:111-114.
79.
Ostergaard SD, Meyers BS, Flint AJ, Mulsant BH, Whyte EM, Ulbricht CM, Bech P, Rothschild AJ; STOP-PD Study Group: Measuring treatment response in psychotic depression: the Psychotic Depression Assessment Scale (PDAS) takes both depressive and psychotic symptoms into account. J Affect Disord 2014;160:68-73.
80.
Ostergaard SD, Lemming OM, Mors O, Correll CU, Bech P: PANSS-6: a brief rating scale for the measurement of severity in schizophrenia. Acta Psychiatr Scand 2016;133:436-444.
81.
Bech P, Wilson P, Wessel T, Lunde M, Fava M: A validation analysis of two self-reported HAM-D6 versions. Acta Psychiatr Scand 2009;119:298-303.
82.
Bech P, Allerup P, Gram LF, Reisby N, Rosenberg R, Jacobsen O, Nagy A: The Hamilton depression scale. Evaluation of objectivity using logistic models. Acta Psychiatr Scand 1981;63:290-299.
83.
Bech P, Allerup P, Reisby N, Gram LF: Assessment of symptom change from improvement curves on the Hamilton depression scale in trials with antidepressants. Psychopharmacology (Berl) 1984;84:276-281.
84.
Bech P, Fava M, Trivedi MH, Wisniewski SR, Rush AJ: Factor structure and dimensionality of the two depression scales in STAR*D using level 1 datasets. J Affect Disord 2011;132:396-400.
85.
Korner A, Lauritzen L, Abelskov K, Gulmann NC, Brodersen AM, Wedervang-Jensen T, Marie Kjeldgaard K: Rating scales for depression in the elderly: external and internal validity. J Clin Psychiatry 2007;68:384-389.
86.
Bech P, Kajdasz DK, Porsdal V: Dose-response relationship of duloxetine in placebo-controlled clinical trials in patients with major depressive disorder. Psychopharmacology (Berl) 2006;188:273-280.
87.
Bech P, Boyer P, Germain JM, Padmanabhan K, Haudiquet V, Pitrosky B, Tourian KA: HAM-D17 and HAM-D6 sensitivity to change in relation to desvenlafaxine dose and baseline depression severity in major depressive disorder. Pharmacopsychiatry 2010;43:271-276.
© 2017 S. Karger AG, Basel
2017
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.