Perspectives Diagnosing Depression in Patients With Medical Illness ROGER
G.
KATHOL. M.D., RUSSELL NOYES. JR .. M.D.
JOHN WtLLlAMS. M.D., ANAND MUTGI. M.D. BRENDAN CARROLL. M.D., PAUL PERRY. PH.D.
Received OclOber4. 19119: revised July 17. 1990: accepted July 17. 1990. From the Departments of Psychiatry.lntemal Medicine. and Pharmacy.Ihe University of Iowa. Iowa City: the Department of tntemal Medicine. Duke Universily. Durham. Norlh Carolina: and .he Department of Internal Medicine. Medical College of Ohio. Toledo. Address reprinl re4uests 10 Dr. Kathol. University of Iowa Hospi(;lls and Clinics. 500 Newton Road. Iowa City. IA 52242. Copyrighl © 1990 The Academy of Psychosomatic Medicine.
4~4
There are many problems associated with the diagnosis of depression in patients with medical illness. First. depressive symptoms are often appropriate to the stress of having a serious medical illness. Even when major depressive criteria are met. psychiatric intervention may not be indicated since the depressive symptoms improve with treatment. Second. many symptoms of depression are similar to those of the medical illness itself (e.g., fatigue. weakness, weight loss. etc.). Discerning whether a symptom should be attributed to the medical illness alone or whether depression is superimposed becomes difficult. Finally. numerous diagnostic systems. I I> which identify overlapping populations. have been proposed to diagnose depression. and some of them are specifically for medically ill patients. Until recently. however.? these criteria had not been tested. Because these problems have not been resolved. the diagnosis of depression in patients with medical illness continues to be made in a variety of ways. Some investigators use depression symptom scales. such as the Beck Depression Inventory (BDI)," the Hamilton Depression Rating Scale (HDRS).'1 or the Center for Epidemiologic Studies-Depression Scale (CES-D)."J Others use DSM-II1-R (DSM-II1) criteria for organic mood (affective) syndrome or adjustment disorder with depressed mood. Many clinicians ignore the fact that organic factors must be excluded in order to make the DSM-II1-R (DSM-III) diagnosis of a major depression. and they use the criteria for this "primary" Disorder as an indication that treatment may be needed. This largely stems from the fact that criteria for organic affective disorder (both DSM-II1 and DSM-II1-R) are so general that they do not define a discrete population. DSM-II1-R refines the DSM-II1 criteria for major depression by stating that a symptom cannot be "due to a physical condition" in order to be counted. Replacement criteria, such as those suggested by Endicott~ (Appendix I). however, are not included. This results in more stringent inclusion criteria for the diagnosis of depression and. therefore. fewer diagnoses of depression.? PSYCHOSOMATICS
Kathol et al.
The variety of approaches to diagnosis suggests that this is a particularly uncertain area in psychiatric classification, despite the fact that depression is presumed to be one of the most common psychiatric conditions seen in primary care patients. I I Some basic questions can be asked which might help clarify this diagnostic dilemma. First, how much do somatic symptoms influence the diagnosis of depression in patients with medical illness? Second, if the symptoms of depression were accepted without regard to whether they were caused by an underlying medical condition, as was suggested in DSM-III, how often would patients be diagnosed differently by the two sets of criteria? And third. can symptom cut-points from the common scales for depression (e.g., a Beck score greater than 13)12 be used to distinguish depressed (those likely to need treatment) from nondepressed patients? If so. what are those cut-points, and how accurately can they identify a depressed patient according to the diagnostic systems currently used in clinical practice? Let us address each of these questions in tum. INFLUENCE OF PSYCHOLOGICAL AND SOMATIC SYMPTOMS Schwab et al. U demonstrated that the psychological symptoms of depression (depressed mood, loneliness, irritability, etc.) frequently are experienced by patients with medical illness, even in the absence of a clinical syndrome of depression. Furthermore, they showed that a cursory psychiatric examination is insufficient to distinguish patients with a depressive symptom complex from other medical patients. In their study, it was only after several depressive symptom report scales were tabulated for each patient that 15% of the medical population could be statistically separated from other medical patients on the basis of a variety of psychological depressive symptoms. These authors also found that somatic symptoms of depression (fatigue, insomnia, anorexia, etc.) frequently were found in the patients that they studied who had medical illness. 14 Fatigue/lethargy, gastrointestinal symptoms, headache. anorexia, recent weight loss. tachycardia. loss of libido, and urinary symptoms all were seen more often in patients thought to have depression (19% of this series). Cavanaugh et al.l~ confirmed that both psychological and somatic symptoms are frequently experienced by patients with medical illness. They, however, went on to compare depressive symptoms in 309 medical patients with the frequency and severity of the same symptoms in 101 patients with major depression diagnosed according to DSM-III criteria. Their analysis revealed that the frequency of psychological symptoms discriminated between the two groups more robustly than did somatic symptoms. When the sel'eriry of somatic symptoms increased. however, a VOLUME 31· NUMBER 4· FALL J990
435
Diagnosing Depression
more depressed population was identified (BOI score greater than 31 ). even in the medically ill. We were able to confirm this finding 7 by showing that. although somatic symptoms are less successful discriminators of criteria-based depression (DSM-III. Research Diagnostic Criteria IRDC!. and Endicott) in the medically ill. patients with depression still have higher somatic symptom scores. The argument put forth above for the impact of somatic symptoms on the diagnosis of depression is somewhat circular. Current criteria include somatic symptoms; therefore. one would expect that the number (or severity) of somatic symptoms in the depressed group would be higher in those identified as depressed. ForexampIe. patients are identified as depressed according to DSM-II1-R criteria only after excluding symptoms related to a physical condition. Using these criteria. we found that although somatic symptoms are seen with slightly greater frequency in patients with major depression. unlike other criteria-based diagnoses there was no significant difference in the somatic symptom scores from the BDI between depressed and nondepressed. 7 Somatic symptoms. therefore. may be of less value in diagnosing depression in the medically ill. but may not be confounders. provided that a sufficient number of psychological symptoms are present. As shall be seen below. somatic symptoms become important when they are excluded from a criteria-based system and not replaced by alternative depressive symptoms. FREQUENCY OF DEPRESSION IN THE MEOICALLY ILLCRITERIA-BASED SYSTEMS This takes us to the next question: How do the different diagnostic systems in current use compare when applied to the same population of patients? Table I shows that different diagnostic systems identify different patients as having major depression. The data in Table I were collected as part of a study of depression in cancer patients. 7 As mentioned previously. a fundamental change in criteria was made between the DSM-II1 and 431>
DSM-II1-R so that the latter excludes depressive symptoms related to a physical condition. In a cohort of 151 cancer patients. this change decreased the number identified as depressed from 57 to 44. The decrease was largely related to the fact that many patients no longer had the required number of depressive symptoms (less than five out of nine). By excluding the physiologic symptoms. DSM-II1-R decreased the numberofsymptoms patients could exhibit and still be considered depressed. but it did not decrease the number of symptoms necessary to meet criteria for a depressive diagnosis. Endicott~ has suggested that when physiologic symptoms of depression are caused by a physical condition. they be replaced by psychological symptoms. The means by which this is done is explained in Appendix I. Such an approach allows the number of criteria necessary for diagnosis to remain the same because the number of symptoms assessed remains consistent. On the other hand. the criteria themselves may vary from one patient to the next. Also it is important that replacement symptoms be of equal validity and reliability to those which are being replaced. However. to date. such an assessment has not been performed. In our studi we were unable to diagnose depression exactly as suggested by Endicott~ because we did not assess emotional reactivity (Appendix I) among our patients. Yet. when three of the four symptoms were replaced by those suggested by Endicott in cases where the physical condition was considered to be an interfering variable. the number identified as depressed was about the same as the number diagnosed by the older DSM-II1 criteria. Only two patients were not concordant (Table I). These findings suggest that. although somatic symptoms are less satisfactory as predictors of the syndrome of major depression. in fact. when coupled with the psychological complaints found in DSM-II1. most of the same patients will meet criteria for depression whether somatic symptoms are replaced by psychological symptoms or not. RDC criteria were the least likely to identify major depression in our cohort. The difference between these and other criteria is in the requirePSYCHOSOMATICS
Kathol et al.
APPJo:N 1>1 X l. Endicott criteria for depression in patients with cancer A.
Dysphoric mood or loss of interest
B.
At least four of the following present at least two weeks (If medical condition is likely to affect a specific symptom. substitute according to items below.) I.
Poor appetite or weight loss'
~
Insomnia or hypersomnia'
.l
Psychomotor agitation or retardation
.t. Loss of interest or pleasure 5.
Loss of energy or fatigue'
o. Feelings of wonhlessness. self-reproach. or guilt 7.
Difficulty thinking or concentrating'
!\.
Thought of death or suicide
C.
Mood-incongruent delusions or hallucinations and hizarre behavior not dominant when affective syndrome absent
D.
NO! superimposed on schizophrenia. schizophrenifoml or paranoid disorder
E.
Not due to organic mental disorder or uncomplicated bereavement 'SuhstilUtion items I. Fearful or depressed appearance ~ Social withdrawal or decreased talkativeness 5. Brooding. self-pity. or pessimism 7. Mood not reactive (i.e .. cannot be cheered up: doesn't smile: no n:action to good news)
ment of five of eight symptoms (rather than four of eight in DSM-III and Endicott criteria and five of nine in DSM-III-R). impairment by the symptoms. and/or the attempt to get help for them. More stringent criteria such as these are essential to use in research designed to determine what role severity plays in response to treatment. natural history. family history. and the like. DEPRESSION SCALE CUT-POINTS Nielsen and Williamsl~ made diagnostic assessments from unstructured clinical interviews according to Feighner criteria '6 in a subset of 41 of 526 outpatients with medical illness. They found that 24 patients had either primary or secondary depression while an additional II had other psychiatric diagnoses. From these 41 patients they VOLUME31.NUMBER4·FALL J990
estimated the sensitivity and specificity of BOI scores of 10 (.92 and .35. respectively), 13 (.79 and .77. respectively), and 17 (.66 and .84. respectively) for clinical depression. They then calculated the best cut-off (BOI score less than 10) for the negative predictive value (i.e.. the probability that a person with a score less than 10 does not have depression). To do this. they used the derived sensitivity and specificity noted above and inserted a 12.2£k prevalence since this is the percentage of patients in their entire sample that had BDI scores of greater than 13 (considered to be mildly depressed). They calculated a negative predictive value of 97% (our calculations indicate 98%), suggesting that the BDI may be an effective tool for excluding those without depression. Many investigators, however, have utilized this and other symptom scales as diagnostic instruments in patients with possible depression associated with medical illness.'~·'5 Perhaps a more important assessment of these instruments. if they are to be used in this way, would be to determine the positive predictive value (i.e.• the probability that a patient with a BDI score greater than a certain value will have depression). Using Bayes's rule '7 at a prevalance level of 20%, as suggested by Schwab et aI., IK the positive predictive values of a BOI score of greater than 10 (for major depression according to Feighner criteria) in the Nielsen and Williams sample is 26%. Thus, 74% of the patients with BDI scores of 10 or greater would not have criteria-based depression according to clinical evaluation. However. the BOI cut-points of 13 and 17 would not be much better at predicting who is depressed (positive predictive value 38% and 50%. respectively). Our sludy of patients with cancer very closely replicates the findings of Nielsen and Williams: I~ however, we employed DSM-III. DSM-III-R. and RDC, instead of the Feighner criteria (Table 2). Also. we found that using psychological items only on the BOI (items I to 14) did not alter the positive predictive value in a meaningful way and that the use of an interviewer-rated scale (HDRS) only altered the positive predictive value when scores of 20 or greater were achieved. Up to this time. figures for prevalence of 437
Diagnosing Depression
depression in the medically ill (10% to 20lf'll) suggested by the use of symptom scales or combinations of scales and clinical assessments. have TARLE t.
I>iallnostic correspondence of major depression accordinll to four diagnostic systems in 151 patients with cancer I>SM-III-R +
DSM-IIJ
+
44 ()
U 94
DSM-IIJ-R + ROC
RI>C +
Endicott +
34 3
23 'II
55 ()
2 94
2X 'I
16 'IX
44 II
0 96
.~2
5 'II
+
23
No',': Values=numbo:r of palients diagnosed as positive (+) or negative (-) for depression; ROC=Research Diagnostic Criteria.
TARLE 2.
been forwarded as reasonable estimates. It can be seen. however. that a substantial percentage of those who fall above symptom scale cutoff scores (e.g.. BDI of 13. HDRS of 15, etc.) are not, in fact. clinically depressed. Could it be that our estimates of the prevalence of depression in the medically ill are intlated? During our study of depression in cancer patients. we screened 768 consecutive outpatients. Five hundred eightynine of these completed the BDI. Of these. 117 had a score of 10 or greater on the BDI. Only 12 of these 117 patients. however. met criteria for major depression according to DSM-III and had scores greater than 18 on the HDRS. The prevalence rate in this outpatient cancer population was 2%. Even if five patients were added to account for the depressed patients who scored below lOon the BDI. as predicted by the negative predictive value. the prevalence rate still would
Questionnaire cut-points for the diagnosis of depression in patients with medical illness Number of Patients True Positive
False Positive
True Nellative
False Negatin
44
U 19 25 IX 24
I 6
2X 44 36 51 40
19 U 7 14 X X 2 26 21 X 22 U 17 10
14 20 29 IX 27
HDRS TOlal~15 HDRS TOlal~20
36 30 23 35 31 41 31
ROC Criteria BDI TOlal~1O BDI Total~U BDI TOlal~19 BDI 1-14~4 BDI 1-14~7 HDRS Total~ 15 HDRS Total~20
2X 25 20 29 24 32 26
35 27 15 29 20 27 16
U 21 33 19 2X
RDl/HI>RS Cut-Points OSM-III Criteria BDI TOlal~IO BDI TOlal~ 13 BDI Total~19 BDI 1-14~4 BDI 1-14~7 HDRS Total~15 HDRS TOlal~20 OSM-III-R Criteria BDI Total~IO BDI Total~U BDI Total~19 BDII-14~4 BDlI-14~7
.W
22 2X
22 29
22 33
17 1 9 2 U
PPV(%1
29 33 40 37 43 47 71
0 5 12 I 5 2 12
2X 29 42 30 40
I
25 27 36 29 33 30 37
4 9 0 5 2 8
.~6
40
Note: BDI=Beck Depression Inventory; HDRS=Hamihon Depression Rating Scale: RDC=Research Diagnostic Criteria: PPV=Positive predictive value assuming a prevalence rate of 20.
PSYCHOSOMATICS
Kathol et al.
be only 2.9%. Such a rate is no different from that seen in the general population when adjusted for the prevalence of dysthymic disorder. I'! The implications of a different prevalence rate for depression in patients with medical illness are at least twofold. First. the positive predictive value of symptom scale scores may be diminished substantially. For instance. using 3%. rather than 20% (used in Table 2). for the prevalence rate decreases the positive predictive value of a BOI score of 19 or greater for DSM-III-R depression from 42% to 8.4%. Second. the story about overlooking depression in medical patients that we have been telling primary physicians for years may be incorrect. It is possible that in our zeal to provide excellent psychiatric care for medical patients. we. the psychiatrists. have intlated the number of patients estimated to have depression. WHERE WE ARE NOW This perspective is intended to provide a nidus from which to pursue further research into depression associated with medical illness. Recent information should help us achieve a better understanding of this type of psychiatric morbidity. First. using the somatic symptoms of depression does not appear to radically intluence the diagnosis of depression in the medically ill. In fact. some of the symptoms probably can be used as discriminators for the presence of depression. albeit less effectively than psychological symptoms. but only when used in conjunction with psychological symptoms of depression. Second. as with primary affective disorders, the diagnostic criteria that are used intluence who is considered depressed and who is not. At the current time. perhaps the best criteria for diagnosing depression in the medically ill are those proposed by Endicott. These adjust for the relationship of somatic symptoms to underlying physical conditions yet do not unduly restrict the identification of depression by simply excluding certain somatic symptoms. For just this reason. DSM-III-R criteria should be viewed as more restrictive when used in patients with medical disease than in patients with primary affective VOLUME." • NUMBER 4· FALL 1990
disorder. The possibility of a type II error (i.e., not diagnosing depression when it is really there) becomes greater with DSM-III-R. The principal problem with the Endicott criteria is that they have not been validated. When one thinks about it. however. the same can be said of all of the available criteria. Patients with medical illness constitute a population with special interfering variables and thus require validation studies of their own. A good example of this can be seen with the Minnesota Multiphasic Personality Inventory. Interpretations based on this validated. structured questionnaire appropriate to the general population cannot be generalized to medically ill populations. ~o Third. the initial task of psychiatrists in assessing medical patients for depression is to consistently identify those who are likely to benefit by a psychiatric intervention. As mentioned previously. many approaches are being used. yet none has been investigated in a systematic fashion. Assessment of the relationship of symptom scale scores to clinical depression as it is understood in primary psychiatric patients suggests that they are poorly correlated. Although symptom scale scores can be used to identify patients who are unlikely to have depression, a clinical psychiatric evaluation is necessary to determine whether criteria-based depression is present. The underlying assumption in this perspective article is that using criteria-based diagnoses ofdepression is inherently better than other methods in the medically ill. Our experience in patients with primary psychiatric disease suggests that this is the case. We have learned that with reproducible diagnoses it is possible to predict such things as who is likely to experience depression. at what point in the course of symptom development treatment is necessary. what is the likelihood of recurrence. and whether family members may be at risk for the development of similar symptoms. When patients with medical illness are assessed for depression using consistent diagnostic parameters. then a similar improvement in our understanding of depression in patients with medical illness will occur. Until an adequate diagnostic system is adopted. however. further progress cannot be made. 4W
Diagnosing Depression
The authors thank Peter Dehelius-Enemark and Dehorah Pfah for assistance in data collection and data management of the work referred
to in this manuscript. The cancer study was supported in part hya grant.from The Upjohll CompallY.
References I. American Psychiatric Association: Diagno.wic and Statistiml Malllwi. 3rd Edition. Washington DC. American Psychiatric Association. 19l17 2. American Psychiatric Association: Diagnostic and Statistical Manual. 3rd Edition. Rt'\·ist'tl. Washinglon DC. American Psychialric Association. 1980 3. Spilzer RL. Endicott J. Robins E: Research Diagnostic Crileria: ralionale and reliability. Arch Gt'n Psychiatn' 35:773-782.197ll 4. Endicott J: Measurement of depression in patients with cancer. Canc('/' 53:2243-224ll. 19l14 5. Cavenaugh S: The diagnosis and trealment of depression in the medically ill. in Manual o/PsychiatricConsultation alltl Enlt'rgencvCart'. Edited by Guggenheim FG. Weiner MF. Dunmore. PA. Jason Aronson. 1984 6. Kathol RG and Petty F: Relationship of depression to medical illness.) Ajft'ctil't' Di.wrd 3: 111-121. 198 I 7. Kathol RG. MUlgi A. Williams J. et al: Major depression diagnosed by DSM-III. DSM-III-R. RDC. and Endicott criteria in pat ients with cancer. Alii ) Psychiatn' 147:1021-1024.1990 ll. Beck AT. Steer RA. Garbin MG: Psychomelric propenies of the Beck depression inventory: twenty-five years of evaluation. Clinical Psychology Rt',·it,... ll:77-IOO. 19l1ll 9. Hamilton M: A rating scale for depression. ) Neurol Nt'urosurg Psychiatry 23:56-62. 1960 10. RadloffL: The CES-D scale: a self repon depression scale for research in lhe general population. Applied PsvcllOlogical Mt'asUI't'lIIt'III I:3ll5--40 I. 1977
440
II. Orleans CT. George LK. HOUpl JL. et al: How primary physicians Ireat psychiatric disorders: a national survey of family practilioners. Alii) Psvchiatry 142:52-57. 19l15 12. Nielsen AC. Williams TA: Depression in ambulatory medical palients: prevalence by self-repon 4uestionnaire and recognilion by nonpsychiatric physicians. Arch Gen P.Hchiall'." 37:999-1004.1980 13. Schwab 11. Bialow MR. Clemmons RS. el al: The affective symptomalology of depression in medical inpatients. P.'ycho.wmatin7:214-217.1966 14. Schwab 11. Clemmons RS. Bialow M. et al: A study of the somatic symplomatology of depression in medical inpalients. PsvcllO.wmatics 6:273-277. 1965 15. Cavanaugh S. Clark DC. Gibbons RD: Diagnosing depression in the hospitalized medically ill. Psycho.wmatics 24:ll09-llI5.19ll3 16. Feighner JP. Robins E. Guze SB. et al: Diagnostic crileria for use in psychiatric research. Arch Gt'n Psvchiatry 26:57--t>3.1972 17. Rosner B: Fundamt'IIIah 01' BioS/ari.win. Boston. Duxbury Press. 19l12 Ill. S,hwab 11. Bialow M. Brown JM. el al: Diagnosing depression in medical inpalienls. Ann 11111'1'11 Med67:695707.1967 )9. Myers JK. Weissman MM. Tischler GL. et al: Six-month prevalence of psychiatric disorders in three communilies. Arch Gen Psychiarrv 41 :959-967. 19l14 20. Osborne D: The MMPI in medical practice. P.Hchiatric Annals 15:534-541. 19l15
PSYCHOSOMATICS
G.
KATHOL. M.D., RUSSELL NOYES. JR .. M.D.
JOHN WtLLlAMS. M.D., ANAND MUTGI. M.D. BRENDAN CARROLL. M.D., PAUL PERRY. PH.D.
Received OclOber4. 19119: revised July 17. 1990: accepted July 17. 1990. From the Departments of Psychiatry.lntemal Medicine. and Pharmacy.Ihe University of Iowa. Iowa City: the Department of tntemal Medicine. Duke Universily. Durham. Norlh Carolina: and .he Department of Internal Medicine. Medical College of Ohio. Toledo. Address reprinl re4uests 10 Dr. Kathol. University of Iowa Hospi(;lls and Clinics. 500 Newton Road. Iowa City. IA 52242. Copyrighl © 1990 The Academy of Psychosomatic Medicine.
4~4
There are many problems associated with the diagnosis of depression in patients with medical illness. First. depressive symptoms are often appropriate to the stress of having a serious medical illness. Even when major depressive criteria are met. psychiatric intervention may not be indicated since the depressive symptoms improve with treatment. Second. many symptoms of depression are similar to those of the medical illness itself (e.g., fatigue. weakness, weight loss. etc.). Discerning whether a symptom should be attributed to the medical illness alone or whether depression is superimposed becomes difficult. Finally. numerous diagnostic systems. I I> which identify overlapping populations. have been proposed to diagnose depression. and some of them are specifically for medically ill patients. Until recently. however.? these criteria had not been tested. Because these problems have not been resolved. the diagnosis of depression in patients with medical illness continues to be made in a variety of ways. Some investigators use depression symptom scales. such as the Beck Depression Inventory (BDI)," the Hamilton Depression Rating Scale (HDRS).'1 or the Center for Epidemiologic Studies-Depression Scale (CES-D)."J Others use DSM-II1-R (DSM-II1) criteria for organic mood (affective) syndrome or adjustment disorder with depressed mood. Many clinicians ignore the fact that organic factors must be excluded in order to make the DSM-II1-R (DSM-III) diagnosis of a major depression. and they use the criteria for this "primary" Disorder as an indication that treatment may be needed. This largely stems from the fact that criteria for organic affective disorder (both DSM-II1 and DSM-II1-R) are so general that they do not define a discrete population. DSM-II1-R refines the DSM-II1 criteria for major depression by stating that a symptom cannot be "due to a physical condition" in order to be counted. Replacement criteria, such as those suggested by Endicott~ (Appendix I). however, are not included. This results in more stringent inclusion criteria for the diagnosis of depression and. therefore. fewer diagnoses of depression.? PSYCHOSOMATICS
Kathol et al.
The variety of approaches to diagnosis suggests that this is a particularly uncertain area in psychiatric classification, despite the fact that depression is presumed to be one of the most common psychiatric conditions seen in primary care patients. I I Some basic questions can be asked which might help clarify this diagnostic dilemma. First, how much do somatic symptoms influence the diagnosis of depression in patients with medical illness? Second, if the symptoms of depression were accepted without regard to whether they were caused by an underlying medical condition, as was suggested in DSM-III, how often would patients be diagnosed differently by the two sets of criteria? And third. can symptom cut-points from the common scales for depression (e.g., a Beck score greater than 13)12 be used to distinguish depressed (those likely to need treatment) from nondepressed patients? If so. what are those cut-points, and how accurately can they identify a depressed patient according to the diagnostic systems currently used in clinical practice? Let us address each of these questions in tum. INFLUENCE OF PSYCHOLOGICAL AND SOMATIC SYMPTOMS Schwab et al. U demonstrated that the psychological symptoms of depression (depressed mood, loneliness, irritability, etc.) frequently are experienced by patients with medical illness, even in the absence of a clinical syndrome of depression. Furthermore, they showed that a cursory psychiatric examination is insufficient to distinguish patients with a depressive symptom complex from other medical patients. In their study, it was only after several depressive symptom report scales were tabulated for each patient that 15% of the medical population could be statistically separated from other medical patients on the basis of a variety of psychological depressive symptoms. These authors also found that somatic symptoms of depression (fatigue, insomnia, anorexia, etc.) frequently were found in the patients that they studied who had medical illness. 14 Fatigue/lethargy, gastrointestinal symptoms, headache. anorexia, recent weight loss. tachycardia. loss of libido, and urinary symptoms all were seen more often in patients thought to have depression (19% of this series). Cavanaugh et al.l~ confirmed that both psychological and somatic symptoms are frequently experienced by patients with medical illness. They, however, went on to compare depressive symptoms in 309 medical patients with the frequency and severity of the same symptoms in 101 patients with major depression diagnosed according to DSM-III criteria. Their analysis revealed that the frequency of psychological symptoms discriminated between the two groups more robustly than did somatic symptoms. When the sel'eriry of somatic symptoms increased. however, a VOLUME 31· NUMBER 4· FALL J990
435
Diagnosing Depression
more depressed population was identified (BOI score greater than 31 ). even in the medically ill. We were able to confirm this finding 7 by showing that. although somatic symptoms are less successful discriminators of criteria-based depression (DSM-III. Research Diagnostic Criteria IRDC!. and Endicott) in the medically ill. patients with depression still have higher somatic symptom scores. The argument put forth above for the impact of somatic symptoms on the diagnosis of depression is somewhat circular. Current criteria include somatic symptoms; therefore. one would expect that the number (or severity) of somatic symptoms in the depressed group would be higher in those identified as depressed. ForexampIe. patients are identified as depressed according to DSM-II1-R criteria only after excluding symptoms related to a physical condition. Using these criteria. we found that although somatic symptoms are seen with slightly greater frequency in patients with major depression. unlike other criteria-based diagnoses there was no significant difference in the somatic symptom scores from the BDI between depressed and nondepressed. 7 Somatic symptoms. therefore. may be of less value in diagnosing depression in the medically ill. but may not be confounders. provided that a sufficient number of psychological symptoms are present. As shall be seen below. somatic symptoms become important when they are excluded from a criteria-based system and not replaced by alternative depressive symptoms. FREQUENCY OF DEPRESSION IN THE MEOICALLY ILLCRITERIA-BASED SYSTEMS This takes us to the next question: How do the different diagnostic systems in current use compare when applied to the same population of patients? Table I shows that different diagnostic systems identify different patients as having major depression. The data in Table I were collected as part of a study of depression in cancer patients. 7 As mentioned previously. a fundamental change in criteria was made between the DSM-II1 and 431>
DSM-II1-R so that the latter excludes depressive symptoms related to a physical condition. In a cohort of 151 cancer patients. this change decreased the number identified as depressed from 57 to 44. The decrease was largely related to the fact that many patients no longer had the required number of depressive symptoms (less than five out of nine). By excluding the physiologic symptoms. DSM-II1-R decreased the numberofsymptoms patients could exhibit and still be considered depressed. but it did not decrease the number of symptoms necessary to meet criteria for a depressive diagnosis. Endicott~ has suggested that when physiologic symptoms of depression are caused by a physical condition. they be replaced by psychological symptoms. The means by which this is done is explained in Appendix I. Such an approach allows the number of criteria necessary for diagnosis to remain the same because the number of symptoms assessed remains consistent. On the other hand. the criteria themselves may vary from one patient to the next. Also it is important that replacement symptoms be of equal validity and reliability to those which are being replaced. However. to date. such an assessment has not been performed. In our studi we were unable to diagnose depression exactly as suggested by Endicott~ because we did not assess emotional reactivity (Appendix I) among our patients. Yet. when three of the four symptoms were replaced by those suggested by Endicott in cases where the physical condition was considered to be an interfering variable. the number identified as depressed was about the same as the number diagnosed by the older DSM-II1 criteria. Only two patients were not concordant (Table I). These findings suggest that. although somatic symptoms are less satisfactory as predictors of the syndrome of major depression. in fact. when coupled with the psychological complaints found in DSM-II1. most of the same patients will meet criteria for depression whether somatic symptoms are replaced by psychological symptoms or not. RDC criteria were the least likely to identify major depression in our cohort. The difference between these and other criteria is in the requirePSYCHOSOMATICS
Kathol et al.
APPJo:N 1>1 X l. Endicott criteria for depression in patients with cancer A.
Dysphoric mood or loss of interest
B.
At least four of the following present at least two weeks (If medical condition is likely to affect a specific symptom. substitute according to items below.) I.
Poor appetite or weight loss'
~
Insomnia or hypersomnia'
.l
Psychomotor agitation or retardation
.t. Loss of interest or pleasure 5.
Loss of energy or fatigue'
o. Feelings of wonhlessness. self-reproach. or guilt 7.
Difficulty thinking or concentrating'
!\.
Thought of death or suicide
C.
Mood-incongruent delusions or hallucinations and hizarre behavior not dominant when affective syndrome absent
D.
NO! superimposed on schizophrenia. schizophrenifoml or paranoid disorder
E.
Not due to organic mental disorder or uncomplicated bereavement 'SuhstilUtion items I. Fearful or depressed appearance ~ Social withdrawal or decreased talkativeness 5. Brooding. self-pity. or pessimism 7. Mood not reactive (i.e .. cannot be cheered up: doesn't smile: no n:action to good news)
ment of five of eight symptoms (rather than four of eight in DSM-III and Endicott criteria and five of nine in DSM-III-R). impairment by the symptoms. and/or the attempt to get help for them. More stringent criteria such as these are essential to use in research designed to determine what role severity plays in response to treatment. natural history. family history. and the like. DEPRESSION SCALE CUT-POINTS Nielsen and Williamsl~ made diagnostic assessments from unstructured clinical interviews according to Feighner criteria '6 in a subset of 41 of 526 outpatients with medical illness. They found that 24 patients had either primary or secondary depression while an additional II had other psychiatric diagnoses. From these 41 patients they VOLUME31.NUMBER4·FALL J990
estimated the sensitivity and specificity of BOI scores of 10 (.92 and .35. respectively), 13 (.79 and .77. respectively), and 17 (.66 and .84. respectively) for clinical depression. They then calculated the best cut-off (BOI score less than 10) for the negative predictive value (i.e.. the probability that a person with a score less than 10 does not have depression). To do this. they used the derived sensitivity and specificity noted above and inserted a 12.2£k prevalence since this is the percentage of patients in their entire sample that had BDI scores of greater than 13 (considered to be mildly depressed). They calculated a negative predictive value of 97% (our calculations indicate 98%), suggesting that the BDI may be an effective tool for excluding those without depression. Many investigators, however, have utilized this and other symptom scales as diagnostic instruments in patients with possible depression associated with medical illness.'~·'5 Perhaps a more important assessment of these instruments. if they are to be used in this way, would be to determine the positive predictive value (i.e.• the probability that a patient with a BDI score greater than a certain value will have depression). Using Bayes's rule '7 at a prevalance level of 20%, as suggested by Schwab et aI., IK the positive predictive values of a BOI score of greater than 10 (for major depression according to Feighner criteria) in the Nielsen and Williams sample is 26%. Thus, 74% of the patients with BDI scores of 10 or greater would not have criteria-based depression according to clinical evaluation. However. the BOI cut-points of 13 and 17 would not be much better at predicting who is depressed (positive predictive value 38% and 50%. respectively). Our sludy of patients with cancer very closely replicates the findings of Nielsen and Williams: I~ however, we employed DSM-III. DSM-III-R. and RDC, instead of the Feighner criteria (Table 2). Also. we found that using psychological items only on the BOI (items I to 14) did not alter the positive predictive value in a meaningful way and that the use of an interviewer-rated scale (HDRS) only altered the positive predictive value when scores of 20 or greater were achieved. Up to this time. figures for prevalence of 437
Diagnosing Depression
depression in the medically ill (10% to 20lf'll) suggested by the use of symptom scales or combinations of scales and clinical assessments. have TARLE t.
I>iallnostic correspondence of major depression accordinll to four diagnostic systems in 151 patients with cancer I>SM-III-R +
DSM-IIJ
+
44 ()
U 94
DSM-IIJ-R + ROC
RI>C +
Endicott +
34 3
23 'II
55 ()
2 94
2X 'I
16 'IX
44 II
0 96
.~2
5 'II
+
23
No',': Values=numbo:r of palients diagnosed as positive (+) or negative (-) for depression; ROC=Research Diagnostic Criteria.
TARLE 2.
been forwarded as reasonable estimates. It can be seen. however. that a substantial percentage of those who fall above symptom scale cutoff scores (e.g.. BDI of 13. HDRS of 15, etc.) are not, in fact. clinically depressed. Could it be that our estimates of the prevalence of depression in the medically ill are intlated? During our study of depression in cancer patients. we screened 768 consecutive outpatients. Five hundred eightynine of these completed the BDI. Of these. 117 had a score of 10 or greater on the BDI. Only 12 of these 117 patients. however. met criteria for major depression according to DSM-III and had scores greater than 18 on the HDRS. The prevalence rate in this outpatient cancer population was 2%. Even if five patients were added to account for the depressed patients who scored below lOon the BDI. as predicted by the negative predictive value. the prevalence rate still would
Questionnaire cut-points for the diagnosis of depression in patients with medical illness Number of Patients True Positive
False Positive
True Nellative
False Negatin
44
U 19 25 IX 24
I 6
2X 44 36 51 40
19 U 7 14 X X 2 26 21 X 22 U 17 10
14 20 29 IX 27
HDRS TOlal~15 HDRS TOlal~20
36 30 23 35 31 41 31
ROC Criteria BDI TOlal~1O BDI Total~U BDI TOlal~19 BDI 1-14~4 BDI 1-14~7 HDRS Total~ 15 HDRS Total~20
2X 25 20 29 24 32 26
35 27 15 29 20 27 16
U 21 33 19 2X
RDl/HI>RS Cut-Points OSM-III Criteria BDI TOlal~IO BDI TOlal~ 13 BDI Total~19 BDI 1-14~4 BDI 1-14~7 HDRS Total~15 HDRS TOlal~20 OSM-III-R Criteria BDI Total~IO BDI Total~U BDI Total~19 BDII-14~4 BDlI-14~7
.W
22 2X
22 29
22 33
17 1 9 2 U
PPV(%1
29 33 40 37 43 47 71
0 5 12 I 5 2 12
2X 29 42 30 40
I
25 27 36 29 33 30 37
4 9 0 5 2 8
.~6
40
Note: BDI=Beck Depression Inventory; HDRS=Hamihon Depression Rating Scale: RDC=Research Diagnostic Criteria: PPV=Positive predictive value assuming a prevalence rate of 20.
PSYCHOSOMATICS
Kathol et al.
be only 2.9%. Such a rate is no different from that seen in the general population when adjusted for the prevalence of dysthymic disorder. I'! The implications of a different prevalence rate for depression in patients with medical illness are at least twofold. First. the positive predictive value of symptom scale scores may be diminished substantially. For instance. using 3%. rather than 20% (used in Table 2). for the prevalence rate decreases the positive predictive value of a BOI score of 19 or greater for DSM-III-R depression from 42% to 8.4%. Second. the story about overlooking depression in medical patients that we have been telling primary physicians for years may be incorrect. It is possible that in our zeal to provide excellent psychiatric care for medical patients. we. the psychiatrists. have intlated the number of patients estimated to have depression. WHERE WE ARE NOW This perspective is intended to provide a nidus from which to pursue further research into depression associated with medical illness. Recent information should help us achieve a better understanding of this type of psychiatric morbidity. First. using the somatic symptoms of depression does not appear to radically intluence the diagnosis of depression in the medically ill. In fact. some of the symptoms probably can be used as discriminators for the presence of depression. albeit less effectively than psychological symptoms. but only when used in conjunction with psychological symptoms of depression. Second. as with primary affective disorders, the diagnostic criteria that are used intluence who is considered depressed and who is not. At the current time. perhaps the best criteria for diagnosing depression in the medically ill are those proposed by Endicott. These adjust for the relationship of somatic symptoms to underlying physical conditions yet do not unduly restrict the identification of depression by simply excluding certain somatic symptoms. For just this reason. DSM-III-R criteria should be viewed as more restrictive when used in patients with medical disease than in patients with primary affective VOLUME." • NUMBER 4· FALL 1990
disorder. The possibility of a type II error (i.e., not diagnosing depression when it is really there) becomes greater with DSM-III-R. The principal problem with the Endicott criteria is that they have not been validated. When one thinks about it. however. the same can be said of all of the available criteria. Patients with medical illness constitute a population with special interfering variables and thus require validation studies of their own. A good example of this can be seen with the Minnesota Multiphasic Personality Inventory. Interpretations based on this validated. structured questionnaire appropriate to the general population cannot be generalized to medically ill populations. ~o Third. the initial task of psychiatrists in assessing medical patients for depression is to consistently identify those who are likely to benefit by a psychiatric intervention. As mentioned previously. many approaches are being used. yet none has been investigated in a systematic fashion. Assessment of the relationship of symptom scale scores to clinical depression as it is understood in primary psychiatric patients suggests that they are poorly correlated. Although symptom scale scores can be used to identify patients who are unlikely to have depression, a clinical psychiatric evaluation is necessary to determine whether criteria-based depression is present. The underlying assumption in this perspective article is that using criteria-based diagnoses ofdepression is inherently better than other methods in the medically ill. Our experience in patients with primary psychiatric disease suggests that this is the case. We have learned that with reproducible diagnoses it is possible to predict such things as who is likely to experience depression. at what point in the course of symptom development treatment is necessary. what is the likelihood of recurrence. and whether family members may be at risk for the development of similar symptoms. When patients with medical illness are assessed for depression using consistent diagnostic parameters. then a similar improvement in our understanding of depression in patients with medical illness will occur. Until an adequate diagnostic system is adopted. however. further progress cannot be made. 4W
Diagnosing Depression
The authors thank Peter Dehelius-Enemark and Dehorah Pfah for assistance in data collection and data management of the work referred
to in this manuscript. The cancer study was supported in part hya grant.from The Upjohll CompallY.
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