Journal of Affective Disorders 150 (2013) 384–388

Contents lists available at ScienceDirect

Journal of Affective Disorders

journal homepage: www.elsevier.com/locate/jad

Research report

Severity classification on the Hamilton depression rating scale

Mark Zimmerman n, Jennifer H. Martinez, Diane Young, Iwona Chelminski,
Kristy Dalrymple
Department of Psychiatry and Human Behavior, Brown Medical School, Rhode Island Hospital, 146 West River Street, Providence, RI, United States

art ic l e i nf o a b s t r a c t

Article history: Background Symptom severity as a moderator of treatment response has been the subject of debate over
Received 31 January 2013 the past 20 years. Each of the meta- and mega-analyses examining the treatment significance of
Accepted 19 April 2013 depression severity used the Hamilton Depression Rating Scale (HAMD), wholly, or in part, to define
Available online 4 June 2013
severity, though the cutoff used to define severe depression varied. There is limited empirical research
Keywords: establishing cutoff scores for bands of severity on the HAMD. The goal of the study is to empirically
Depression establish cutoff scores on the HAMD in their allocation of patients to severity groups.
Severity Methods Six hundred twenty-seven outpatients with current major depressive disorder were evaluated
Hamilton depression rating scale with a semi-structured diagnostic interview. Scores on the 17-item HAMD were derived from ratings
according to the conversion method described by Endicott et al. (1981). The patients were also rated on
the Clinical Global Index of Severity (CGI). Receiver operating curves were computed to identify the cutoff
that optimally discriminated between patients with mild vs. moderate and moderate vs. severe
depression.
Results HAMD scores were significantly lower in patients with mild depression than patients with
moderate depression, and patients with moderate depression scored significantly lower than patients
with severe depression. The cutoff score on the HAMD that maximized the sum of sensitivity and
specificity was 17 for the comparison of mild vs. moderate depression and 24 for the comparison of
moderate vs. severe depression.
Limitations The present study was conducted in a single outpatient practice in which the majority of
patients were white, female, and had health insurance. Although the study was limited to a single site, a
strength of the recruitment procedure was that the sample was not selected for participation in a
treatment study, and exclusion and inclusion criteria did not reduce the representativeness of the patient
groups. The analyses were based on HAMD scores extracted from ratings on the SADS. However, we used
Endicott et al.'s (1981) empirically established formula for deriving a HAMD score from SADS ratings, and
our results concurred with other small studies of the mean and median HAMD scores in severity groups.
Conclusions Based on this large study of psychiatric outpatients with major depressive disorder we
recommend the following severity ranges for the HAMD: no depression (0–7); mild depression (8–16);
moderate depression (17–23); and severe depression (≥24).
& 2013 Elsevier B.V. All rights reserved.

1. Introduction Health and Clinical Excellence (NICE) updated guidelines for the
treatment and management of depression discouraged the use of
The importance of severity in selecting and evaluating the efficacy antidepressant medication as the initial treatment option for mild
of treatment for depressed patients has received increased attention depression, and recommended medication together with empirically
recently. The Third Edition of the American Psychiatric Association's supported psychotherapy for moderate and severe depression
(APA's) guidelines for the treatment of major depressive disorder (National Collaborating Center for Mental Health, 2009). As reported
recommended both psychotherapy and pharmacotherapy as mono- by van der Lem et al. (2011), treatment guidelines in the Netherlands
therapies for depression of mild and moderate severity, and pharma- also recommended pharmacotherapy as the first treatment option for
cotherapy (with or without psychotherapy) for severe depression severely depressed patients, and either pharmacotherapy or psy-
(American Psychiatric Association, 2010). The National Institute for chotherapy for mildly and moderately depressed patients. While the
recommendations in these guidelines are not entirely consistent, they
n are unanimous in recommending medication as the treatment of
Corresponding author. Tel.: 1 401 444 7098.
E-mail address: mzimmerman@lifespan.org (M. Zimmerman). choice for severe depression.

0165-0327/$ - see front matter & 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jad.2013.04.028
 M. Zimmerman et al. / Journal of Affective Disorders 150 (2013) 384–388 385

Symptom severity as a moderator of treatment response has define the severity categories. In none of the discussion sections of
been the subject of ongoing debate since the publication of the these reports were questions raised about the cutoffs used to
results from the National Institute of Mental Health Treatment of define the grades of severity. The APA's Handbook of Psychiatric
Depression Collaborative Research Program (TDCRP) suggesting Rating Scales (Rush et al., 2008) cited two studies in support of the
that psychotherapy was not as effective as medication in the acute cutoff scores to identify severity subtypes. One was a study
treatment of severe depression (Elkin et al., 1995, 1989). In 1999, examining the validity of deriving a HAMD equivalent score on
DeRubeis et al. (1999) noted that treatment guidelines from the the Schedule for Affective Disorders and Schizophrenia (Endicott
American Psychiatric Association (1993) and Agency for Health et al., 1981). In fact, this study did not attempt to determine the
Care Policy and Research (1993) recommended antidepressant cutoff scores on the HAMD indicating grades of severity. Rather,
medication, and not psychotherapy, for severe depression, and when examining the agreement between the extracted and
these recommendations were largely based on the findings of the original HAMD in classifying patients into severity categories, the
TDCRP. The importance of severity was recently renewed in authors used a cutoff of 25 to indicate severe depression (and a
another context—the range of effectiveness of antidepressant cutoff of 18 to distinguish mild and moderate depression). The
medication. Kirsch et al. (2008) conducted a meta-analysis of second study cited as evidence for using a cutoff of 23 to indicate
antidepressant treatment trials in the FDA data base and found severe depression examined the association between HAMD
that drug-placebo differences increased as baseline severity scores and global ratings of severity in 59 depressed inpatients
increased, and concluded that antidepressants were only mini- (Kearns et al., 1982). The authors did not derive (or recommend)
mally more effective than placebo for mildly and moderately cutoff scores corresponding to severity levels. In Figure 2 of their
depressed patients. This conclusion was reinforced by the results paper, the authors graphed the mean HAMD for patients rated at
of a mega-analysis of 6 studies by Fournier et al. (2010), though a different levels of severity. Visual inspection of this figure suggests
recent, larger, mega-analysis found that the efficacy of two anti- that very severe depression corresponded to a mean HAMD score
depressants, fluoxetine and venlafaxine, over placebo was inde- of approximately 29 and severe depression corresponded to a
pendent of severity (Gibbons et al., 2012). The severity of mean HAMD score of 21. If these groups were combined, the mean
depression has also continued to retain importance in moderating HAMD for the severe category would be approximately 25. Thus, it
the effect of psychotherapy, though a recent meta-analysis of is unclear why a cutoff of 19 was recommended in the APA
psychotherapy studies found that greater symptom severity did Handbook to identify severe depression. We are aware of only
not predict poorer response in controlled studies examining the 2 other small studies comparing HAMD scores to clinical global
moderating effect of severity (Driessen et al., 2010). severity ratings. Knesevich et al. (1977) evaluated a sample of 26
Each of these meta- and mega-analyses used the Hamilton outpatients, 9 of whom were rated in the severe range. Visual
Depression Rating Scale (HAMD) (1960), wholly, or in part, to define inspection of the figure plotting the distribution of scores suggests
severity, though the cutoff used to define severe depression varied. that the median score for these patients was 24. Muller et al.
DeRubeis et al. (1999) conducted a mega-analysis of 4 studies (2003) evaluated 85 depressed inpatients, 26 of whom were rated
comparing cognitive-behavioral therapy and medication. Following severe. The results of a receiver operating curve analysis to
the precedent of the TDRCP, DeRubeis et al. defined severe depres- determine the optimal cutoff score on the HAMD to indicate
sion as a cutoff of 20 or more on the 17-item HAMD. Likewise, the severe depression found that a cutoff of 25 provided the best
recent mega-analysis of placebo-controlled trials of fluoxetine and balance of sensitivity and specificity.
venlafaxine cited the TDRCP in using a cutoff 420 to define severe There is thus a limited amount empirical research establishing
depression. Of note, no empirical justification was given in the cutoff scores for bands of severity on the HAMD. Because of the
TDRCP for using this threshold to define severe depression (Elkin significance accorded severity by treatment guidelines it is impor-
et al., 1989). In fact, Elkin et al.'s (1989) did not refer to the patients tant to empirically establish cutoff scores on the HAMD in the
scoring above 20 on the HAMD in absolute terms (i.e., having severe allocation of patients to severity groups. Accordingly, in the
depression), but instead referred to them in relative terms (i.e., present report from the Rhode Island Methods to Improve Diag-
having more severe depression than the patients scoring 20 and nostic Assessment and Services (MIDAS) project we compared
below). In Kirsch et al. (2008) meta-analysis the authors noted that HAMD scores to clinician global ratings of severity in a large
the mean baseline HAMD scores of the antidepressant efficacy trials sample of depressed outpatients.
were in the very severe range (i.e., ≥23 based on the APA's Hand-
book of Psychiatric Measures (Rush et al., 2008) for all but 2 of the
35 studies included in the analysis. Prior to the report by Kirsch and 2. Methods
colleagues, Khan et al. (2002) examined the FDA data base, and also
found that drug-placebo differences increased with increasing The Rhode Island MIDAS project represents an integration of
mean baseline HAMD scores. Khan et al. (2002) divided the studies research methodology into a community-based outpatient prac-
into 3 groups based on pretreatment HAMD scores (≤24, 25–27, tice affiliated with an academic medical center (Zimmerman,
≥28) without indicating the basis for using these cutoff scores to 2003). A comprehensive diagnostic evaluation is conducted upon
define the groups. Fournier et al. (2010) used the thresholds presentation for treatment. This private practice group predomi-
recommended in the APA's Handbook of Psychiatric Measures nantly treats individuals with medical insurance (including Med-
(Rush et al., 2008) to define grades of severity on the HAMD (mild icare but not Medicaid) on a fee-for-service basis, and it is distinct
to moderate≤18; severe 19 to 22; very severe ≥23). from the hospital's outpatient residency training clinic that pre-
In contrast to all of these studies, and the APA guidelines, most dominantly serves lower income, uninsured, and medical assis-
pharmacotherapy studies have used a cutoff of 25 on the 17-item tance patients. Data on referral source was recorded for the last
HAMD to define severe depression (Dunner et al., 2005; Kasper, 1600 patients enrolled in the study. Patients were most frequently
1997; Montgomery et al., 2003; Schmitt et al., 2009; Shelton et al., referred from primary care physicians (30.0%), psychotherapists
2007; Versiani et al., 2005), and this cutoff has been recommended (16.1%), and family members or friends (18.8%). The Rhode Island
by several experts to define severe depression (Hirschfeld, 1999; Hospital institutional review committee approved the research
Montgomery and Lecrubier, 1999; Schatzberg, 1999). protocol, and all patients provided informed, written consent.
Fundamental to all of these studies on the treatment implica- The patients were interviewed by a diagnostic rater who
tions of severity is the validity of the cutoffs on the HAMD to administered a modified version of the Structured Clinical
386 M. Zimmerman et al. / Journal of Affective Disorders 150 (2013) 384–388

Interview for DSM-IV (SCID) (First et al., 1995). Integrated into the Table 1
interview were the symptom severity items from the Schedule for Sensitivity and Specificity of the 17-item Hamilton Depression, Rating Scale in
Distinguishing Mild vs. Moderate and Moderate, vs. Severe Depression.
Affective Disorders and Schizophrenia (SADS) (Endicott and
Spitzer, 1978). During the course of the study we modified our HAMD Score Mild vs. Moderate Moderate vs. Severe
assessment procedure at various times, and not all of the SADS
items were rated throughout the study. The present report is Sensitivity Specificity Sensitivity Specificity
based on the 627 patients with current major depressive disorder
o 10 97.0 6.4 99.1 3.0
for whom we could derive scores on the 17-item HAMD from the 11 93.7 17.0 98.3 6.3
SADS items according to the conversion method described by 12 91.3 25.5 98.3 8.7
Endicott et al. (1981). The patients were also rated on the Clinical 13 87.4 29.8 95.7 12.6
Global Index of Severity (CGI) (Guy, 1976). The CGI and SADS 14 82.2 36.2 94.0 17.8
15 74.4 51.1 92.2 25.6
ratings were based on symptom severity during the week prior to
16 67.5 55.3 88.8 32.5
the evaluation. The 627 patients included 220 (35.1%) men and 17 60.5 66.0 84.5 39.5
407 (64.9%) women who ranged in age from 18 to 78 years 18 53.1 70.2 82.8 46.9
(mean¼ 41.2, SD ¼12.3). Approximately two-fifths of the subjects 19 45.1 76.6 79.3 54.9
were married (42.4%, n ¼266); the remainder were single (27.0%, 20 38.0 83.0 73.3 62.0
21 31.7 83.0 68.1 68.3
n ¼169), divorced (17.5%, n ¼110), separated (5.3%, n ¼33), 22 25.2 87.2 62.1 74.8
widowed (2.1%, n ¼ 13), or living with someone as if in a marital 23 19.1 91.5 55.2 80.9
relationship (5.7%, n ¼36). Approximately two-thirds of the 24 13.7 95.7 50.9 86.3
patients attended school beyond high school (62.8%, n ¼394), 25 10.0 95.7 41.4 90.0
26 6.9 95.7 36.2 93.1
though only one-quarter graduated a 4-year college (31.6%,
27 5.4 97.9 31.9 94.6
n ¼198). The racial composition of the sample was 88.2% 28 4.3 97.9 25.0 95.7
(n ¼553) white, 5.6% (n ¼35) black, 3.8% (n ¼24) Hispanic, 3.8% 29 3.0 97.9 17.2 97.0
(n ¼24) Asian, and 1.4% (n ¼ 9) from another or a combination of 30 2.2 100.0 12.1 97.8
the above racial backgrounds. 31 1.5 100.0 7.8 98.5
32 1.3 100.0 5.2 98.7
Endicott et al. (1981) computed an extracted HAMD score from
SADS ratings for the 21-item version of the HAMD. They developed
a table converting item scores on the SADS into HAMD equivalent
scores. We used their conversion table to compute an extracted sensitivity and specificity was 17 for the comparison of mild vs.
17-item HAMD score. moderate depression (sensitivity ¼60.5%, specificity ¼66.0%) and
24 for the comparison of moderate vs. severe depression
2.1. Statistical analysis (sensitivity ¼50.9%, specificity ¼86.3%).

We determined cutoff scores on the HAMD corresponding to

CGI severity ratings by conducting a receiver operating curve 4. Discussion
(ROC) analysis (Hsiao et al., 1989). An ROC curve is a plot of a
measure's sensitivity versus one minus specificity at each cut-off Treatment guidelines for depression suggest that it is impor-
score. We conducted 2 sets of analyses, first comparing patients tant to consider severity when selecting a patient's initial treat-
with mild and moderate depression, and then comparing patients ment modality (American Psychiatric Association, 2010; National
with moderate and severe depression. Collaborating Center for Mental Health, 2009; van der Lem et al.,
2011). That is, for severely depressed patients the guidelines
indicate that pharmacotherapy is the treatment of choice, whereas
3. Results for mildly and moderately depressed patients both pharmacother-
apy and psychotherapy are recommended options. While the
The mean score on the CGI was 3.1 (SD ¼.5) corresponding to a moderating effect of severity on the differential efficacy of med-
moderate level of severity. A small number of patients were rated ication and therapy has received relatively little empirical atten-
extremely depressed (.8%, n ¼5), and these patients were included tion (Driessen et al., 2010; Elkin et al., 1995), the fact that official
in the severe group. The majority of the patients were rated as treatment guidelines have based treatment recommendations on
having moderate depression (73.5%, n ¼461). More patients were severity distinctions highlights the clinical importance of valid
rated as having severe depression (18.5%, n ¼116) than mild assessment of this variable.
depression (7.5%, n ¼47). Two patients were rated as having For all scales measuring the severity of depressive symptoms
minimal depression during the week prior to the evaluation and the thresholds distinguishing patients with mild, moderate, and
were excluded from subsequent analyses. The mean 17-item severe depression do not represent well-demarcated lines separ-
HAMD was 18.8 (SD ¼5.6). A one-way analysis of variance compar- ating the severity subtypes. As with other areas of psychopathol-
ing HAMD scores in patients rated mild, moderate, and severe on ogy, the severity of depression better corresponds to a
the CGI was significant (F ¼28.3, 2622 df, p o.001). HAMD scores dimensional than a categorical model of classification (Ruscio
were significantly lower in patients with mild depression than et al., 2007). Consistent with this, the results of the present study
patients with moderate depression (15.3 74.9 vs. 18.1 75.1, t¼ found that while the severity groups significantly differed on the
−3.7, p o.001), and patients with moderate depression scored HAMD, the distribution of scores in each severity group over-
significantly lower than patients with severe depression lapped. Nonetheless, treatment selection recommendations based
(18.1 75.1 vs. 23.0 75.7, t ¼−9.0, p o.001). on severity distinctions rely on a categorical approach whereby
In the ROC analysis, the areas under the curve (AUCs) compar- certain treatments are suggested for patients falling into particular
ing mild vs. moderate depression and moderate vs. severe depres- severity groupings.
sion were significant (mild vs. moderate, AUC¼.66, p o.001; The HAMD has been the most frequently used scale to
moderate vs. severe, AUC¼.74, p o.001). The data in Table 1 shows subdivide patients into severity groups and examine the treatment
that the cutoff score on the HAMD that maximized the sum of implications of symptom severity. It is therefore surprising that so
 M. Zimmerman et al. / Journal of Affective Disorders 150 (2013) 384–388 387

Table 2 Our analyses were based on HAMD scores extracted from ratings
Recommended Ranges of Scores on the 17-Item Hamilton Depression, Rating Scale on the SADS. However, we used Endicott et al. (1981) empirically
(HAMD) Corresponding to Levels of Severity.
established formula for deriving a HAMD score from SADS ratings,
Depression Severity HAMD Range of Scores and our results concurred with other small studies of the mean
and median HAMD scores in severity groups. A strength of the
None 0–7 study is that the patients were recruited from routine clinical
Mild 8–16 practice, and did not pass through the inclusion/exclusion criteria
Moderate 17–23
Severe ≥24
filters that are used in most treatment studies. This avoids the
inflation bias that might operate in such studies in order to qualify
patients for inclusion. Also, in contrast to treatment studies, a
minimum HAMD severity score was not required for inclusion.
little research has examined the validity of the cutoffs used to Other strengths of the study are the use of highly trained
demarcate the bands of severity. Perhaps for this reason there has interviewers to reliably administer the clinician rated assessments
been heterogeneity in the cutoffs used to define severity levels. and the large sample size.
In the present study of patients meeting criteria for major
depressive disorder we focused on the distinction between mild
and moderate and moderate and severe depression. We did not Role of funding source
None.
examine the distinction between mild and no depression, or
between mild and minimal depression, because there has been a
relative consensus to define remission from depression as a HAMD
Conflict of interest
score of 7 and below (Frank et al., 1991). To be sure, there has been None.
increasing research suggesting that minimal levels of symptoms
are associated with increased risk of relapse, impaired psychoso-
cial functioning, and reduced quality of life, thereby suggesting Acknowledgments
that the threshold to define remission (i.e., the absence of depres- None.
sion) should be lower than 7 on the HAMD (Judd et al., 2000;
Riedel et al., 2010; Zimmerman et al., 2005, 2007). However, in the References
absence of research more clearly defining the upper and lower
bounds of minimal depression, we limit our recommendations for
Agency for Health Care Policy and Research, 1993. Clinical practice guideline:
ranges of severity to no depression, mild, moderate and severe depression in primary care, treatment of major depression. In: Research,
depression (Table 2). Agency for HealthCare Policy (Ed.), US Government Printing Office.
The cutoff of 24 for severe depression is close to the cutoff of 25 American Psychiatric Association, 1993. Practice Guideline for Major Depressive
Disorder in Adults. American Psychiatric Association, Washington, DC.
that has been recommended by experts (Hirschfeld, 1999; American Psychiatric Association, 2010. Practice Guideline for the Treatment of
Montgomery and Lecrubier, 1999; Schatzberg, 1999) and the cutoff Patients With Major Depressive Disorder. American Psychiatric Association,
most frequently used in pharmacotherapy studies (Dunner et al., Washington, DC.
DeRubeis, R.J., Gelfand, L.A., Tang, T.Z., Simons, A.D., 1999. Medications versus
2005; Kasper, 1997; Montgomery et al., 2003; Schmitt et al., 2009; cognitive behavior therapy for severely depressed outpatients: mega-analysis
Shelton et al., 2007; Versiani et al., 2005). Of note, this cutoff is of four randomized comparisons. American Journal of Psychiatry 156,
higher than the cutoff of 19 recommended in the APA Handbook of 1007–1013.
Driessen, E., Cuijpers, P., Hollon, S.D., Dekker, J.J., 2010. Does pretreatment severity
Rating Scales (Rush et al., 2008). As we summarized in the moderate the efficacy of psychological treatment of adult outpatient depres-
introduction, only two studies were cited in support of a cutoff sion? A meta-analysis. Journal of Consulting and Clinical Psychology 78,
of 19 to define severe depression, and a review of these two 668–680.
Dunner, D., Lipschitz, A., Pitts, C., Davies, J., 2005. Efficacy and tolerability of
studies suggested that the cutoff to define severe depression controlled-release paroxetine in the treatment of severe depression: post hoc
should be either 24 or 25 (Kearns et al., 1982; Knesevich et al., analysis of pooled data from a subset of subjects in four double-blind clinical
1977). Thus, our findings regarding the cutoff to define severe trials. Clinical Therapeutics 27, 1901–1911.
Elkin, I., Gibbons, R., Shea, M., Sotsky, S., Watkins, J., Pilkonis, P., 1995. Initial
depression are consistent with the previous small studies compar-
severity and differential treatment outcome in the National Institute of Mental
ing HAMD scores to CGI ratings. Health Treatment of Depression Collaborative Research Program. Journal of
The cutoffs used to define severity categories have implications Consulting and Clinical Psychology 63, 841–847.
for interpreting studies of the efficacy of antidepressants and the Elkin, I., Shea, M., Watkins, J., Imber, S., Sotsky, S., Colllins, J., Glass, D., Pilkonis, P.,
Leber, W., Docherty, J., Fiester, S., Parloff, M., 1989. NIMH treatment of
moderating effect of severity on treatment selection and outcome. depression collaborataive research program: general effectiveness of treat-
Studies using a cutoff of 20 to define severe depression have ments. Archives of General Psychiatry 46, 971–982.
included a large number of moderately depressed patients within Endicott, J., Cohen, J., Nee, J., Fleiss, J., Sarantakos, S., 1981. Hamilton depression
rating scale. Archives of General Psychiatry 38, 98–103.
the severe group. Looking at our own sample, the majority (64.3%) Endicott, J., Spitzer, R.L., 1978. A diagnostic interview: the schedule for affective
of patients scoring 20 or more on the HAMD would fall into the disorders and schizophrenia. Archives of General Psychiatry 35, 837–844.
moderate depression group. Thus, suggestions that psychotherapy First, M.B., Spitzer, R.L., Gibbon, M., Williams, J.B.W., 1995. Structured Clinical
Interview for DSM-IV Axis I Disorders—Patient edition (SCID-I/P, version 2.0)..
may be as effective as pharmacotherapy in treating severe depres- Biometrics Research Department, New York State Psychiatric Institute, New
sion, or that antidepressants are only effective for severe depres- York.
sion, may be erroneous because the majority of patients Fournier, J.C., DeRubeis, R.J., Hollon, S.D., Dimidjian, S., Amsterdam, J.D., Shelton, R.
C., Fawcett, J., 2010. Antidepressant drug effects and depression severity: a
considered to have severe depression may, in fact, have been patient-level meta-analysis. Journal of the American Medical Association 303,
moderately depressed. 47–53.
The strengths and limitations of the study should be acknowl- Frank, E., Prien, R., Jarrett, R., Keller, M., Kupfer, D., Lavori, P., Rush, A., Weissman, M.,
1991. Conceptualization and rationale for consensus definitions of terms in
edged. The study was conducted in a single clinical practice in
major depressive disorder. Archives of General Psychiatry 48, 851–855.
which the majority of the patients were white, female, and had Gibbons, R.D., Hur, K., Brown, C.H., Davis, J.M., Mann, J.J., 2012. Benefits From
health insurance. Replication in samples with different demo- antidepressants: synthesis of 6-week patient-level outcomes from double-
graphic characteristics is warranted. The study was limited to blind placebo-controlled randomized trials of fluoxetine and venlafaxine.
Archives of General Psychiatry 69, 572–579.
examining grades of severity on the 17-item HAMD. Different Guy, W., 1976. ECDEU Assessment Manual for Psychopharmacology. National
cutoffs would be appropriate for longer versions of the scale. Institute of Mental Health, Rockville, MD.
388 M. Zimmerman et al. / Journal of Affective Disorders 150 (2013) 384–388

Hamilton, M., 1960. A rating scale for depression. Journal of Neurology Neurosur- Riedel, M., Moller, H.J., Obermeier, M., Schennach-Wolff, R., Bauer, M., Adli, M.,
gery and Psychiatry 23, 56–62. Kronmuller, K., Nickel, T., Brieger, P., Laux, G., Bender, W., Heuser, I., Zeiler, J.,
Hirschfeld, R., 1999. Efficacy of SSRIs and newer antidepressants in severe depres- Gaebel, W., Seemuller, F., 2010. Response and remission criteria in major
sion: Comparison with TCAs. Journal of Clinical Psychiatry 60, 326–335. depression—a validation of current practice. Journal of Psychiatric Research
Hsiao, J.K., Bartko, J.J., Potter, W.Z., 1989. Diagnosing diagnoses: receiver operating 44, 1063–1068.
characteristic methods and psychiatry. Archives of General Psychiatry 46, Ruscio, J., Zimmerman, M., McGlinchey, J.B., Chelminski, I., Young, D., 2007.
664–667. Diagnosing major depressive disorder XI: a taxometric investigation of the
Judd, L., Paulus, M., Schettler, P., Akiskal, H., Endicott, J., Leon, A., Maser, J., Mueller, structure underlying DSM-IV symptoms. Journal of Nervous and Mental Disease
T., Solomon, D., Keller, M., 2000. Does incomplete recovery from first lifetime 195, 10–19.
major depressive episode herald a chronic course of illness? American Journal Rush, A.J., First, M.B., Blacker, D., 2008. Handbook of Psychiatric Measures.
of Psychiatry 157, 1501–1504. American Psychiatric Publishing, Inc., Washington.
Kasper, S., 1997. Efficacy of antidepressants in the treatment of severe depression: Schatzberg, A.F., 1999. Antidepressant effectiveness in severe depression and
the place of mirtazapine. Journal of Clinical Psychopharmacology 17 (Suppl. 1), melancholia. Journal of Clinical Psychiatry 60 (Suppl. 4), 14–21, discussion 22.
19S–28S. Schmitt, A.B., Bauer, M., Volz, H.P., Moeller, H.J., Jiang, Q., Ninan, P.T., Loeschmann, P.
Kearns, N.P., Cruickshank, C.A., McGuigan, K.J., Riley, S.A., Shaw, S.P., Snaith, R.P., A., 2009. Differential effects of venlafaxine in the treatment of major depressive
disorder according to baseline severity. European Archives of Psychiatry and
1982. A comparison of depression rating scales. British Journal of Psychiatry
Clinical Neuroscience 259, 329–339.
141, 45–49.
Shelton, R.C., Prakash, A., Mallinckrodt, C.H., Wohlreich, M.M., Raskin, J., Robinson,
Khan, A., Leventhal, R.M., Khan, S.R., Brown, W.A., 2002. Severity of depression and
M.J., Detke, M.J., 2007. Patterns of depressive symptom response in duloxetine-
response to antidepressants and placebo: an analysis of the Food and Drug
treated outpatients with mild, moderate or more severe depression. Interna-
Administration database. Journal of Clinical Psychopharmacology 22, 40–45.
tional Journal of Clinical Practice 61, 1337–1348.
Kirsch, I., Deacon, B.J., Huedo-Medina, T.B., Scoboria, A., Moore, T.J., Johnson, B.T.,
van der Lem, R., van der Wee, N.J., van Veen, T., Zitman, F.G., 2011. The general-
2008. Initial severity and antidepressant benefits: a meta-analysis of data
izability of antidepressant efficacy trials to routine psychiatric out-patient
submitted to the Food and Drug Administration. PLoS Medicine 5, 0260–0268. practice. Psychological Medicine 41, 1353–1363.
Knesevich, J.W., Biggs, J.T., Clayton, P.J., Ziegler, V.E., 1977. Validity of the Hamilton Versiani, M., Moreno, R., Ramakers-van Moorsel, C.J., Schutte, A.J., 2005. Compar-
rating scale for depression. British Journal of Psychiatry 131, 49–52. ison of the effects of mirtazapine and fluoxetine in severely depressed patients.
Montgomery, S., Ferguson, J.M., Schwartz, G.E., 2003. The antidepressant efficacy of CNS Drugs 19, 137–146.
reboxetine in patients with severe depression. Journal of Clinical Psychophar- Zimmerman, M., 2003. Integrating the assessment methods of researchers in
macology 23, 45–50. routine clinical practice: The Rhode Island Methods to Improve Diagnostic
Montgomery, S.A., Lecrubier, Y., 1999. Is severe depression a separate indication? Assessment and Services (MIDAS) project. In: First, M. (Ed.), Standardized
European Neuropsychopharmacology 9, 259–264. Evaluation in Clinical Practice. American Psychiatric Publishing, Inc, Washing-
Muller, M.J., Himmerich, H., Kienzle, B., Szegedi, A., 2003. Differentiating moderate ton, DC, pp. 29–74.
and severe depression using the Montgomery-Asberg depression rating scale Zimmerman, M., Posternak, M., Chelminski, I., 2005. Is the cutoff to define
(MADRS). Journal of Affective Disorders 77, 255–260. remission on the Hamilton Rating Scale too high? Journal of Nervous and
National Collaborating Center for Mental Health, 2009. Depression: the treatment Mental Disease 193, 170–175.
and management of depression in adults. In: National Institute for Health and Zimmerman, M., Posternak, M.A., Chelminski, I., 2007. Heterogeneity among
Clinical Excellence (Ed.), National Institute for Health and Clinical Excellence, depressed outpatients considered to be in remission. Comprehensive Psychia-
London, England, p. 64. try 48, 113–117.