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Journal ofAffectiveDisorders, 14 1988) 161-170Elsevier 161

JAD 00524

The Diagnostic Melancholia Scale (DMS) :dimensions of endogenous and reactive depressionwith relationship to the Newcastle Scales

P. Beth, P. Allerup, L.F. Gram, P. Kragh-Serrensen, O.J. Rafaelsen, N. Reisby,P. Vestergaard and the Danish University Antidepressant Group (DUAG) *

Fr ederiksborg General Hospital, DK-3400 Hi llem Denmark(Received 5 August 1987)

(Accepted 13 October 1987)

Summary

The two diagnostic Newcastle Scales for depression have been evaluated in a drug trial with antide-pressants. By use of latent structure analysis (Rasch models) it was found that two dimensions arenecessary for describing the diagnosis of depression, one for endogenous features and one for reactivefeatures. Of the depressed patients 50% had a pure endogenous depression, 14% had a pure reactivedepression, 32% had mixed endogenous and reactive depression, and 4% had uncertain diagnosis. In thepure endogenous depression group 77% had a monotonically non-decreasing improvement curve duringtreatment whereas in the other diagnostic categories around 50% had such an improvement.

Key worak Newcastle Depression Scale; Depression dimensions

Introduction

Among the diagnostic scales for depression wehave previously analysed the two Newcastle Scales

* Members: J. Andersen, P. Beth, S. Benjaminsen, M. Bjerre,S. BBjholm, P. Christensen, A. Gjerris, L.F. Gram, L.Hansted, E. Jensen, P. Kragh-Sorensen , C.B. Kristensen, P.Kyneb, D. Loldrup, O.F. Madsen, O.L. Pedersen, O.J.Rafaelsen, S. Rasmussen, N. Reisby I, F. Sevaj, P. Simon-sen, H.Y. Thomsen, P. Vestergaard . Steering committee.Address for correspondence: Per Beth, Frederiksborg Gen-

era1 Hospital, DK-3400 Hillernd, Denmark.

(Carney et al., 1965; Gurney, 1971; Beth et al.,1983; Roth et al., 1983). In our first study (Beth etal., 1980) we found no significant correlation be-tween the Hamilton Depression Scale (Hamilton,1967) and the Newcastle Scales when assessingpatients prior to antidepressant therapy, therebystressing the fact that the Hamilton DepressionScale (HDS) and the Newcastle Scales rate twodifferent aspects of depression, severity and diag-nosis, respectively. Of the two Newcastle Scalesthe 1965 version containing 10 items (Carney etal., 1965) is the most frequently used scale inclinical research. The 1971 version (Gurney, 1971)

0165-0327/88/$03.50 0 1988 Elsevier Science Publishers B.V. (Biomedical Division)

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contains 10 items for the diagnosis of endogenousversus reactive depression, which were, however,originally applied secondary to a subdivision ofpatients into anxious and depressed (e.g., Kragh-Serensen et al., 1973; Roth et al., 1983; Mullaney,1985). We developed more explicit item specifica-tions for the Newcastle Scales than the originalinstructions (Beth et al., 1983), but we discardedthe initial subgrouping where patients with ananxiety score are excluded from a further diagno-sis of depression.

The Newcastle Scales have been criticised byEysenck (1970) for containing two subscales which,by differential weights (positive and negative) todifferent items, are transferred to only one bipolardimension of endogenous versus reactive depres-sion. This criticism has, in our opinion, not beenconclusively analysed. The background for thecriticism is outlined in Fig. 1, where the Newcastlecontinuum is indicated as a one-dimensional sub-space of the two-dimensional classification withthe one axis containing items indicative of endoge-nous depression and the other axis containingitems indicative of reactive depression. For thiscontinuum to properly reflect the different posi-tions of the two-dimensional system, the two axes

cd 123 5 6 7 a 910

Newcastle continuumof depresmnFig. 1. The diagnostic diagram showing the position of fourhypothetical patients on the two dimension endogenous andreactive depression, and on the Newcastle continuum. Patientsc and d have the same score on the Newcastle scale althoughthey are widely different on the two-dimensional representa-

tion. Modified after Eysenck (1970).

need to show simple mathematical relationships.In fact, it is not otherwise possible to distinguishpatients with high scores on both axes from pa-tients with low scores on the two axes - patientsd and c in Fig. 1 who received identical Newcastlescores. However, the results found by Carney etal. (1965) seem to indicate that patient d in Fig. 1does not exist, i.e., the distribution of scores alongthe Newcastle continuum is bimodal.

The Newcastle Scales, furthermore, containitems for measuring delusions, which narrow theirapplicability to inpatients, and most of the de-pressed patients are now treated in general prac-tice. In our opinion endogenous depression is notsynonymous with psychotic depression. With thisbackground we have reconsidered the two New-castle Scales. We selected ten items from the scalesof which five items are indicative of endogenousdepression, and the other five items are indicativeof reactive depression. In an earlier study (Beth etal., 1984a), we found that these items maintainedthe same level of interobserver reliability when weused equal weighting of items as when we used thedifferential weights originally found by Carney etal. (1965) or Gurney (1971).

In this study we have, prior to the analysis ofrelations between the two axes, undertaken twoseparate item analyses by means of Rasch modelsin order to examine whether endogenous and reac-tive scores are sufficient statistics for the twodimensions.

Methods

atientsThe sample consists of 95 patients who entered

a double-blind, 35-day between-group comparisonof clomipramine and citalopram. The methodol-ogy and results have been reported elsewhere(DUAG, 1986). In this multicentre study 102hospitalised patients suffering from a major de-pression (a HDS score of 18 or more, or a score of9 or more on our HDS subscale, Beth et al., 1975)participated. In the present study we includedthose patients in whom both Newcastle Scaleswere completed during the placebo wash-outperiod, prior to the 35-day active treatment, intotal 95 patients. Of the 95 patients 64 were

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female and 31 were male. Their ages ranged be-tween 24 and 67 years, median 51 years.Raters

In total 15 psychiatrists took part in the trial.These raters have been described elsewhere (Bethet al., 1986) with regard to such variables as yearsof experience in psychiatry, experience with andattitude to rating scales, sex, and place of work.The interobserver reliability expressed by intra-class coefficients of all 15 psychiatrists of theNewcastle Scales on the basis of joint interviewswith ten patients was 0.57 for the 1965 versionand 0.34 for the 1971 version P < 0.01, DUAG,1986). However, the number of raters per patientin this reliability study ranged from two to 13.Furthermore, three of the raters together assessed41 of the 95 patients in the trial. The interobserverreliability of these three raters was 0.69 for the1965 version of the Newcastle Scales, 0.50 for the1971 version, 0.62 for the five endogenous items ofthe Diagnostic Melancholia Scale (DMS), and 0.51for the five reactive items P < 0.01).The Diagnostic Melancholia Scale DMS)

The two axes consist of 10 items in total. Allitems are scored on a 3-point response scale (0 =not present; 1 = doubtful or very slight; and 2 =mild to severe). The endogenous part contains thefollowing items: quality of depression, feelingworse in the morning, early waking, weight loss,and persistence of clinical picture. The reactivepart contains the remaining five items: psycho-logical stressors, reactivity of symptoms, characterdeviations, somatic anxiety, and duration of cur-rent episode. Each axis ranges from 0 to 10, as thetotal score is measured as item (O-2) multiplied bythe number of items (5). It should be emphasisedthat none of the 10 DMS items are included in ourHDS subscale, which measures the severity ofdepressive states. For the specific instructions ofthe DMS, see Appendix.Statistical analysis

The Rasch model (Rasch, 1960, 1966; Fischer,1974) for multicategory item response calibrationis a general theory for the relation between mani-fest (clinical) item responses and latent (theoreti-cal) dimensions. The link between manifest item

responses and the latent dimension is definedthrough a requirement of statistical sufficiency,i.e., the requirement that the item responses canbe additively combined to a total score. If thesetotal scores are sufficient statistics, the next stepin the analysis is to see whether there exists asimple mathematical relationship between thescores in the two-dimensional diagnostic system,i.e., to examine whether the two dimensions areparallel in the sense that less endogenous meansmore reactive.

We have previously described the mathematicalaspects of the general Rasch model when analys-ing data from rating scales of depression (Beth etal., 1981; Allerup, 1986), and it has been shownhow to obtain simple one-dimensional compari-sons from the general multicategory Rasch model.Testing procedures are initiated as likelihood ratiotests for the general model (Andersen, 1973) inwhich case general homogeneity among scale itemsis investigated. Subsequent tests of the one-dimen-sional Rasch model are based on subdivisions ofitems (homogeneity) and patients (transferability)either by means of internal test criteria (scorelevel) or by external patient characteristics such assex and age. The likelihood ratio tests are allperformed at a level of significance of P = 0.05.

The DMS items are defined in the Appendix,and it should be noted that the item responses areordered, i.e., an item response of 2 means that apatient has also obtained a response of 1 on thisitem. The one-dimensional Rasch model assessesquantitative scorings of these qualitative responserankings, and it is part of the statistical analysis totest whether these scores differ significantly fromthe equidistant calibration: 0, 1, and 2.esults

Both the five items constituting the endogenousaxis of depression and the five items definingreactive depression passed the tests for the generalRasch model and the subsequent test of one-di-mensionality, as all x2 values were insignificant atthe 5% level of statistical significance. It wasestimated that the scoring system for the itemcategories not present, doubtful or very mild,and mild to severe was 0.0, 1.2, and 2.0 for theendogenous dimension, and 0.0, 1.5, and 2.0 for

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the reactive dimension. However, we could notreject the hypothesis P -c .05)f equidistantcalibration: 0.0, 1.0, and 2.0, and the furtheranalyses were based on this calibration system.

The relative significance of the five items withinthe endogenous dimension could be evaluated byRasch analysis in relation to the calibrated itemresponses: 0, 1, and 2. We found that most pa-tients scored on the item of early waking, nextcame quality of depression, weight loss, per-sistence of clinical picture, and the most exclusiveitem was feeling worse in the morning.

Likewise, the five items within the reactive di-mension could be ranked by Rasch analysis. Wefound that most patients scored on the item ofduration of current episode, next came psycho-logical stressors, reactivity of symptoms, char-acter deviations, and the most exclusive item wassomatic anxiety.

It is a powerful property of the Rasch analysisthat beyond these rankings, quantitative weightscan be obtained. In fact, we found that around85% of the expected contribution to the endoge-nous scores was due to the item feeling worse inthe morning. For the reactive dimension, around80% of the expected contribution was due to theitems character deviations and somatic anxiety.

The distribution of the Newcastle 1965 andNewcastle 1971 scores of the 95 patients wereboth clearly unimodal. For Newcastle 1965 wefound a mean score of 6.5 (standard deviation:2.2), the median was 7.0 (range 0.5-11). For New-castle 1971 we found a mean score of -25.3(standard deviation of 15.7), the median was -27.3(range 15.5- - 51.5).

In Fig. 2 we show the distribution of scores ofthe 95 patients in accordance with Fig. 1. Usingcut-off scores of 5 on each of the two dimensionsit appears that 31 patients were type d patients asdefined by Fig. 1. Only four patients were classi-fied as type c patients. It is clear (Fig. 2) that nosimple mathematical relationship between the twodimensions emerged. This proves that the twodimensions cannot without loss of information bereduced to a single underlying continuum, as pre-sumed by the Newcastle Scales.

In Fig. 3 we show the distribution (percentage)of patients within the four diagnostic categoriesderived from our two-dimensional diagram. As

1 .. . 1. . .

a

Fig. 2. The score distribution of the 95 patients according tothe diagnostic diagram shown in Fig. 1. Using cut-off scores of5 on each of the two dimensions, 47 patients scored 5 or moreon the endogenous dimension and less than 5 on the reactivedimension (pure endogenous depression), 31 patients scored 5or more on both dimensions (mixed endogenous and reactivedepression), 13 patients scored 5 or more on the reactivedimension and less than 5 on the endogenous dimension (purereactive depression), and four patients scored less than 5 on

both dimensions (uncertain diagnosis).

can be seen, type a patients (endogenous depres-sion) accounted for 49.5%, type b patients (reac-tive depression) for 13.7%, type c patients (uncer-tain diagnosis) for 4.2%, and type d patients (mixedendogenous and reactive depression) for 32.6%.This classification is based on pretreatment rat-ings (week 0). We have investigated this pretreat-ment classification in relation to the posttreatmentmeasurements of severity of depression (weeksl-6) by use of our HDS subscale transformed tothe three degrees of severity, no depression,minor depression, and major depression, con-sidered relevant in trials with antidepressants(Beth et al., 1984b). It can be seen from Fig. 3that the original distribution over the diagnosticcategories was found to be very stable over theweeks of treatment, namely around 50% endoge-nous depression, around 14% reactive depression,around 32% mixed endogenous and reactive de-pression, and around 4% uncertain depression.

In contrast, the pretreatment Newcastle 1971classification of 73% endogenous depression and27% reactive depression was found to vary consid-erably from week to week and within the threedegrees of depressive states (Fig. 4). The same

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42. 1 42. 1

t i i0.0 15. 8

NO Minor

week 5

50. 0 28.9

El 7.9 13.2week k

week 3

week 2

49. 5 33. 0

t - i - l4.4 13. 2week 1

Maj or

week 0

Fig. 3. The distribution (in percent) of the pretreatment scores (week 0) on the DMS (a = pure endogenous depression; b = purereactive depression; d = mixed endogenous and reactive depression; and c = uncertain diagnosis) in relationship to the severityclassification by the Hamilton Depression Subscale score (no depression = O-3; minor depression = 4-8; and major depression = 9

or more).

results were obtained with Newcastle 1965, indi-cating an association between diagnosis and sever-ity.

Finally, we analysed the predictive validity ofour two-dimensional scales (DMS) with regard toresponse to treatment. We have previously argued(Beth et al., 1984b) that improvement curves forpatients with endogenous depression during treat-ment with antidepressants should have a mono-tonic shape, indicating a steady time-dependentimprovement towards recovery. In contrast, pa-tients with reactive depression should have less

clearly time-dependent improvement curves. Wehave, therefore, analysed the percentage of pa-tients with steady time-dependent improvementcurves (i.e., patients who week after week duringthe trial have no worsening) in each of the threediagnostic categories of endogenous depression(type a), reactive depression (type b), and mixedendogenous and reactive depression (type d). Thenumber of patients in the uncertain group (type c)was too small for statistical analysis.

Using our HDS subscale transformed to threedegrees of severity (no depression = complete re-

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endogenous and reactive depression should beseparated from the construct of severity of depres-sion. In a review of the universe of diagnosticitems for depression (Beth and Allerup, 1986) it isshown that the works of Lewis (1934) and Kendell(1968) lack such items as quality of depression,feeling worse in the morning, early waking, andpersistence of clinical picture (i.e., around 80% ofthe items of endogenous depression in DMS).Neither Lewis nor Kendell at the time of theirinvestigations accepted the concept of endogenousdepression. In contrast, Paykel (1971) includedmost of the items of endogenous depression foundin DMS in his studies on the classification ofdepressed patients. In his subsequent studies(Paykel, 1972, 1977) he found that patients withendogenous depression had the best outcome onamitriptyline compared with other subgroups ofdepression. Both Lewis, Kendell, and Paykel in-cluded all five reactive items found in the DMS.

The validity of the Newcastle Scales was con-sidered promising in some studies (e.g., Beth, 1981)but rather negative in other studies (e.g., Katsch-nig et al., 1986). In this study we found that theconstruct validity of the DMS was superior to theNewcastle Scales, as no interaction between DMSand severity of depression emerged, in contrast tothe Newcastle Scales (Fig. 3). It is difficult toevaluate the predictive validity of diagnostic ratingscales in controlled clinical trials because patientswho are able to complete the fixed treatmentprocedure in the obsessive multicentre protocolsalready by their common feature of adhering tothe protocol neutralise their pretreatment dif-ferences in the clinical profile of depression (Bethet al. 1984b). However, in the present multicentrestudy we were able to demonstrate a superiority ofDMS compared to the Newcastle Scales concern-ing an aspect of predictive validity. Hence, amajority of patients with DMS endogenous de-pression had non-decreasing improvement curves,whereas this was only the case in half of thepatients with reactive depression. The mixed groupof endogenous and reactive depression seemedcloser in this respect to the reactive than to theendogenous group. However, an end-point analy-sis of outcome to treatment showed no statisticallysignificant differences between these three di-agnostic groups of patients. As stated by Wing

(1978) it is an attractive theory to regard mixedendogenous and reactive depression as a biologicaldisorder of lower vulnerability than pure endoge-nous depression, because the biological dis-turbance in the mixed group only shows clinicalmanifestations when provoked by psychosocialstressors. The DMS opens possibilities for studiesin this field, in contrast to the Newcastle Scaleswhere the concept of psychoprovoked endogenousdepression is lacking.

Further studies will clarify the predictive valid-ity of DMS. The conceptual or construct validityof DMS was found acceptable in this study. Itsapplicability in general practice where most de-pressed patients are now treated is under investi-gation.

ppendix

SCORING INSTRUCTIONS FOR THE DI-AGNOSTIC MELANCHOLIA SCALE (DMS)Item 1 Quality of depression O-2)

This item includes the patients experience ofthe current depressive episode as qualitatively dis-tinct from normal despondency when under ad-versity or distress, e.g., the death of a loved one.The patient should, therefore, be asked for quali-tative feelings different from the range of his orher ordinary affective responses to adversity. It isa difficult item to assess, especially, of course, ifthe patient denies ever having had severe adversi-ties. It is of importance to ensure whether prior tothe current depressive episode, i.e., in the habitualstate, the patient has experienced the same kind ofsymptoms as now or whether the current symp-toms are more of a foreign body, a distinctquality of depression.

If the patient cannot identify himself/herselfwith the current depressive syndrome, whichtherefore is conceived as qualitatively distinct fromfeelings of grief, the score is 2. If the intervieweror the patient are in doubt whether this item ispresent, the score is 1. If the current depressive-episode has been described as ordinary tristesseas experienced in adverse situations like deathwithin the family or circle of friends, the score is0.

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Item 2 Early awakening O-2)Early awakening implies that the patient wakes

up at least one hour earlier than usual. The assess-ment of this item should include the general(average) sleep pattern during the current depres-sive episode, and not only the last days. N.B. It isimmaterial whether the patient has been usingsedative/hypnotic medication or not

When the interviewer is convinced that duringthe actual episode as a persistent feature the pa-tient has woken up at least one hour too early, thescore is 2. When in doubt, or when the patient hasonly had this symptom during the last few days,the score is 1. If early awakening has not beenpresent, the score is 0.Item 3 Weight loss O-2)

When the patient indicates a weight loss of 3 kgor more related to the current depressive episode,or 0.5 kg or more per week during the last 3weeks, the score is 2. At less pronounced weightloss, the score is 1, and with no weight loss relatedto the current episode, the score is 0.Item 4 Diurnal variation, feeling worse in the morn-ing O-2)

Diurnal variation implies that during the cur-rent depressive episode the patient has generally(on average) been most depressed in the morninghours, and that the severity diminishes during theday. The criterion for diurnal variation is notfulfilled if the patient only indicates having ashort-lasting amelioration just before going to bed.

When the interviewer is convinced that duringthe current episode the patient has had diurnalrhythmicity in the severity of his or her symptoms,the score is 2 (cross-examine to take habitualdiurnal variation and possible reactivity intoaccount ). When it is doubtful whether a trulyautonomous diurnal variation is present, the scoreis 1. When there is no diurnal rhythmicity, thescore is 0.Item 5 Persistence of clinical picture O-2)

This item implies that the clinical picture, thedepressive syndrome, in general has been constantduring the current episode, apart from smallerday-to-day variations and/or diurnal variation.

If there has been no significant change (fluctua-

tions between good or bad days or weeks), thescore is 2. If it is more doubtful whether per-sistence has been present during the current epi-sode, the score is 1. If there have been clearfluctuations, the score is 0.Item 6 Psychological stressors O-2)

Psychological stressors imply any situation orevent which is considered by the interviewer tohave been a significant contributor to the develop-ment of the current depressive episode. The stres-sors must have appeared within the last 6 monthsprior to this episode, and may or may not still bepresent and maintaining the depressive syndrome.The stressors may be worries concerning oneshealth, worries concerning the health of near rela-tives or friends, a death of a loved one, interper-sonal conflicts in the family or at work, andfinancial problems. The same stressor will, ofcourse, be a very different experience for the dif-ferent patients, and the patients subjective experi-ences and feelings must be taken into considera-tion. However, the interviewers evaluation is deci-sive.

If psychological stressors have been or are stillpresent, the score is 2. If the interviewer is indoubt, the score is 1. If psychological stressorshave not been present, the score is 0.Item 7 Reactivity O-2)

Reactivity means that the severity of the de-pressive symptoms waxes and wanes in relation tocircumstances, e.g., the patient feels less depressedwhen something pleasent or positive appears ortakes place. The patient thus retains the capacityto react positively when something positive takesplace and/or to feel less depressed for a while ingood company.

When the interviewer is convinced that reactiv-ity is present, the score is 2. If reactivity is onlyvery transient, the score is 1. If there is lack ofreactivity to usually pleasurable stimuli, that is thepatient does not feel much better, even tempor-arily, when something good happens, the score is0.Item 8 Somatic anxiety O-2)

Somatic anxiety should be assessed indepen-dently of the coexistence of psychic anxiety.

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Somatic anxiety includes all physiological con-comitants of anxiety: motor tension and/or auto-nomic hyperactivity (especially palpitations,nausea or vomiting, sweating, and dizziness). It isoften difficult to distinguish between somaticanxiety and psychomotor agitation, but in thisconnection it is immaterial whether agitation isincluded in the score. It is also immaterial todistinguish between attacks of somatic anxietyand generalized anxiety. It is, however, decisive toassess whether during the current depressive epi-sode the patient has experienced somatic anxiety,and the last week should be stressed most.

If during the last week and/or during the inter-view the patient has been clearly anxious (expe-rienced motor tension, palpitations, nausea, sweat-ing etc.), the score is 2. If in doubt, the score is 1.If the patient has not experienced somatic anxiety,the score is 0.

Item 9 Duration of current episode O-2)Duration of current episode is noted from the

time when the patient first experienced a clearchange from normal life or mood to the time ofinvestigation. If the illness is phasic, the currentepisode must have been preceded by a clear ill-ness-free interval of at least 3 months.

If the current episode has lasted 1 year or more,the score is 2. If the episode has lasted between 6and 12 months, the score is 1. If the episode haslasted less than 6 months, the score is 0.

Item 10 Character neurosis O-2)Character neurotic features might have emerged

before the current episode from the patients choiceof spouse or life partner (a peaceful or consideratepartner rather than a dominating or self-assertivepartner) because character neurotics avoid personswho provoke them. During the current episode theneurotic features might have manifested them-selves in the way the patient is presenting his orher complaints, namely by striving for an emo-tional secondary gain. At the interview this striv-ing can be observed by the patients cooperationon an attention-demanding dimension.

If the patient has shown clear signs of characterneurosis, the score is 2. If it is more uncertain forthe interviewer that the patient has a character

neurosis, the score is 1. If the patient has no signof character neurosis, the score is 0.

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