Research report
What does the HAMD mean?

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Abstract

Little is known about the clinical relevance of the Hamilton Rating Scale for Depression (HAMD-17) total scores. It is unclear how total scores translate into clinical severity, or what commonly used measures for response (reduction from baseline of ≥50% in the total score) and remission (total HAMD-17 score ≤7) mean from a clinical perspective. We therefore compared: (a) the percentage and absolute change in the HAMD-17 total scores with Clinical Global Impression-Improvement (CGI-I); (b) the absolute and percentage change in the HAMD-17 total scores with Clinical Global Impression-Severity (CGI-S) absolute change; and (c) the percentage and absolute change in the HAMD-17 total scores with CGI-I in the subgroups of patients with≤median and>median HAMD-17 total scores at baseline. The method used was equipercentile linking of HAMD-17 and CGI ratings from 43 drug trials in patients with Major Depressive Disorder (MDD) (n=7131). Our results confirm the validity of the commonly used measures for remission and response in MDD trials: a CGI-I score of 2 (‘much improved’) corresponded to a reduction from baseline of >50% and <60%, and a CGI-I score of 1 (‘very much improved’) to a reduction of >75% and <85%. The CGI-S score of 1 (‘normal., not at all ill’) corresponded to the HAMD-17 total score of <5 and the CGI-S score of 2 (‘borderline mentally ill’) to the score between 6 and 8. An effect of baseline illness severity was observed.

Introduction

The Hamilton Rating Scale for Depression (HAMD; Hamilton, 1967) is a 17-item clinician rated instrument developed to quantify the severity of depression in subjects already diagnosed with this disorder. Despite some criticism (Bagby et al., 2004), it became one of the most widely used outcome measure in depression, utilized in many trials of new antidepressants submitted to the Food and Drug Administration (FDA) (Kobak, 2004). Another frequently used clinician rated instrument in depression research, the Clinical Global Impressions Scale (CGI; Guy, 1976, Busner and Targum, 2007), describes a patient's overall clinical state as a global impression. It separates between the patient's illness severity (CGI-S) on a scale from 1 to 7, and change from baseline on an improvement scale (CGI-I, formerly CGI-Change; details see below). It thus provides information about the clinical relevance of changes observed during treatment. It has been shown that CGI appears to be intuitively understood by clinicians, achieving good inter-rater reliability (Nierenberg and DeCecco (2001)). HAMD is therefore a long measure with strong psychometric properties, whereas the CGI is short and has clinical meaning. It has been demonstrated that a substantial correlation exists between the HAMD and other frequently used clinician rated scales used in depression (for review see Kobak, 2004), such as the Montgomery Åsberg Depression rating Scale (MADRS, Montgomery and Åsberg, 1979), the Global Assessment Scale (GAS, Endicott et al., 1976) or the Beck Depression Inventory (Beck et al., 1961). Overall, there is consensus that a total score of 7 or 8 on the HAMD-17 is the cut-off between asymptomatic and symptomatic status (Frank et al., 1991). Response is usually defined as at least 50% reduction from baseline total score (Furukawa et al., 2002); remission as a HAMD score of 6 or less (Riedel et al., 2010). However, few studies have examined the validity of such, mostly expert opinion-based definitions (Furukawa et al., 2007). Henkel et al found response and remission rates to vary depending on the instrument used to assess severity in a multi-center study (Henkel et al., 2011). Yet, little is known about the clinical relevance of HAMD-17 total scores, in terms of their correspondence with clinically judged severity. In other words, how globally ill does a clinician judge someone to be who has a HAMD score of, for example, 18 or 25. How much does a clinician really notice a HAMD reduction of, say 50% of the patient's baseline total score (Furukawa et al., 2007, Spielmans and McFall, 2006). The CGI was designed to give answers to these questions, but has not yet been linked to HAMD scores. There is a lot of clinical utility in the ability to link such scales (Rabinowitz et al., 2010, Goodman et al., 2010, Velthorst et al., in press), as it allows the nominal translation of vast amounts of data into other scales, adding significantly to the available clinical data for various treatments without the need for new trials. Lepping et al have used previous linkage studies analyzing the nominal translation of Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) into CGI scores to examine the clinical relevance of antipsychotic medication (Lepping et al., 2011).

The purpose of this study was to find corresponding points for simultaneous HAMD-17 and CGI ratings within a large sample of patients with Major Depressive Disorder (MDD) who were participating in drug trials.

Section snippets

Materials and methods

The clinical trial data used for this study come from studies conducted with full sponsorship from Organon (now: Merck, Sharpe and Dohme, MSD). Mirtazapine was used as a treatment in placebo controlled, comparator controlled or open-label trials in patients with Major Depressive Disorder (MDD). We examined absolute as well as percentage reductions from baseline in HAMD-17 total scores and correlated them with CGI-Severity of Illness (CGI-S) and CGI-Improvement (CGI-I) scores, using the

Results

We identified 43 studies (1 dose finding study, 4 placebo controlled studies, 6 placebo and active compound controlled studies, 20 direct comparisons between mirtazapine and another antidepressant and 12 open-label studies). The study data was received courtesy of Organon for the independent use in our group. Our database includes all available studies from Organon (now: Merck, Sharpe and Dohme, MSD) on mirtazapine. Included patients had a diagnosis of a MDD according to Diagnostic and

Discussion

Our analysis was based on over 7000 individual patients. We found that a CGI-S score of 1 (‘normal, not at all ill’) corresponded to a HAMD-17 total score of <5 and a CGI-S score of 2 (‘borderline mentally ill’) to a HAMD-17 total score between 6 and 8, thus confirming currently used measures for remission in MDD studies (total HAMD-17 score of ≤7). Furthermore, our analysis supports the HAMD criterion for response (reduction of ≥50% from baseline on the total HAMD-17), as a CGI-I score of 2

Role of funding source

There was no external funding for this project.

Conflict of interest

HF, MK and AS work full-time for Merck & Co, parent company of Organon, which provided the data for this study. AS is also a share holder with Merck & Co. SL has received honoraria for consulting/advisory boards from Alkermes, BristolMyersSquibb, EliLilly, Janssen, Johnson&Johnson, Lundbeck, Medavante, Roche, lecture honoraria from AstraZeneca, BristolMyersSquibb, EliLilly, EssexPharma, Janssen, Johnson&Johnson, Lundbeck Institute, Pfizer, SanofiAventis, and EliLilly has provided medication for

Acknowledgments

We thank Milana Zivkov, MD, for her help in writing the manuscript.

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