Chronic pain and depression. IV. DST as a discriminator between chronic pain and depression

Pain, 28 (1987) 39-44 Elsevier

39

PA1 00986

Chronic pain and depression. IV. DST as a discriminator between chronic pain and depression Randal D. France, K. Ranga Rama Krishnan, Mary Trainor * and Susan Pelton Department

of Psychiatry and * Department of Nursing, Duke University Medical Center, Durham, NC 27710 (U.S.A.) (Received

30 April 1986, accepted

16 June 1986)

Summary

In an attempt to clarify the relationship between chronic pain and depression, the authors studied the plasma cortisol response to dexamethasone in a group of 73 consecutive chronic low back pain patients admitted to a pain unit and 34 consecutive patients admitted to an affective disorders unit with the principal diagnosis of primary major depression. Patients with chronic pain were evaluated as to the presence or absence of major depression and patients with primary major depression were evaluated as to the presence or absence of pain complaints as part of their presenting symptomatology. Chronic pain patients with major depression differed significantly from chronic pain patients without major depression (3.45 3.33 pg/dl versus 1.6 kO.9 pg/dl, P < 0.05). Chronic pain patients with major depression also differed from patients with primary major depression with pain complaints (3.4* 3.3 pg/dl versus 10.7* 8 rg/dl, P < 0.0005). The values given are post-dexamethasone plasma cortisol levels. Patients having primary major depression with pain complaints do not significantly differ from patients having primary major depression without pain complaints. The dexamethasone suppression test may be a useful method in discriminating those patients with chronic pain versus those with primary major depression, chronic pain patients with major depression versus those with primary major depression and chronic pain patients with major depression versus those with chronic pain and no depression. Key words:

chronic

pain;

depression;

dexamethasone

suppression

test; chronic

low back pain

Introduction The relationship between chronic pain and depression has become enmeshed in the literature. Depression is often found in chronic pain syndromes [7,12-151.

Correspondence to: Randal D. France, M.D., Assistant Medical Center, Box 3903, Durham, NC 27710, U.S.A.

0304-3959/87/$03.50

0 1987 Elsevier Science Publishers

Professor

of Psychiatry,

B.V. (Biomedical

Division)

Duke

University

However. the exact relationship remains unclear. In this series of articles [9.10]. uc have shown that different types of depression can occur in chronic low back pain patients. We previously studied the clinical characteristics of depression in these patients and have shown that the different subtypes can be clearly discriminated on the basis of these clinical characteristics from each other and from chronic pain patients without depression [4). Chronic low back pain patients who develop major depression have a higher familial incidence of major depression (8). This suggests a genetic vulnerability to the development of depression. We have also shown in earlier reports that chronic pain patients without depression could be differentiated from chronic pain patients with major depression using the dexamethasone suppression test (DST) [5.6]. Atkinson et al. [l] and Syvalakti et al. [16] recently reported similar findings. The question still remains whether the major depression seen in chronic pain patients differs from the major depression unrelated to chronic pain. Patients with the principal diagnosis of major depression often have pain complaints [17]. It is interesting to speculate whether these patients are similar to chronic pain patients with major depression and, additionally, whether patients with primary major depression and pain complaints differ from patients with primary major depression and without pain complaints. In this study we examined 2 questions: (1) Do chronic pain patients with major depression differ from patients with the principal diagnosis of primary major depression on the DST? (2) Do patients with primary major depression having pain complaints differ from patients with primary major depression without pain complaints on the DST?

Method Seventy-three consecutive patients admitted to an inpatient pain unit with chronic low back pain were studied. Of these, 34 patients satisfied DSM-III criteria [3] for major depression, 5 for dysthymic disorder, and 34 did not satisfy criteria for any affective disorder. Thirty-eight consecutive patients admitted to the Affective Disorders Unit with the principal diagnosis of primary major depression (DSM-III) were studied. Of these patients, 14 had associated pain complaints such as headaches, myalgias, low back pain, abdominal pain, and chest pain. All patients were thoroughly examined for somatic pathology. The examination included orthopedic and neurosurgical evaluation, electromyography, computerized tomography and myelography. Inclusion criterion was the presence of daily occurring low back pain for more than 6 months in duration. In addition, the presence or absence of organic pathology was determined. Organic pathology was defined as having one of the following findings: (1) physical examination positive for radiculopathy, (2) abnormal radiographic findings, or (3) positive electromyography. Patients admitted to the Affective Disorders Unit had a psychiatric history and examination at time of admission by the attending psychiatrist and resident physician. A diagnosis using DSM-III was made by the attending psychiatrist. The charts were reviewed by one of the co-authors (R.F.) who was blind to the results of the

DST and final diagnosis was made to insure that diagnostic criteria were met. The presence or absence of pain complaints were systematically obtained by the admitting physician as part of the standard physical examination and interview. The following exclusion criteria were used for chronic pain patients: (1) schizophrenia, (2) alcoholism, (3) personality disorder, and (4) recurrent unipolar depression or bipolar illness. The following exclusion criteria were used for patients with primary major depression: (1) pain problem prior to the onset of depression such as migraine headaches, low back pain, abdominal pain, etc., (2) physical illness or trauma preceding or precipitating the depression, (3) schizophrenia, (4) bipolar disorder, (5) alcohol or substance abuse, and (6) personality disorder. The exclusion criteria for the DST include the following: (1) schizophrenia or bipolar illness, (2) alcoholism, (3) recent use of reserpine, steroids, phenobarbital, meprobamate, diphenylhydantoin, carbamazepine and high dose benzodiazepines or opioid analgesics, (4) acute incapacitating illness or recent fever, (5) a weight loss of more than 20 pounds, (6) pregnancy, (7) obesity, (8) a significant hepatic, renal or cardiac disease, (9) uncontrolled diabetes mellitus, (10) past history of encephalitis, (11) organic brain syndrome, (12) renal vascular hypertension, (13) temporal lobe epilepsy, (14) high dose steroids, and (15) other endocrine diseases. The reasons for excluding patients with any of the above mentioned conditions have been described by Carroll et al. [2]. The DST was done l-5 days after admission for all patients. The only medication received by any of the patients was tricyclic antidepresants and non-opioid analgesics. The dexamethasone suppression test was administered as follows: 1 mg of dexamethasone was given at 23.00 h and plasma cortisol was obtained the following day at 16.00 h and 22.00 h. Plasma cortisol was measured by competitive protein binding method [2]. The samples were assayed without knowledge of the clinical diagnosis. The DST results were studied in respect to major depression and presence or absence of pain complaints.

Results

The 5 chronic pain patients with dysthymic disorder were excluded from further data analysis. The mean age for chronic pain patients was 52 + 8.7 years and it was not significantly different from patients with the principal diagnosis of primary major depression (mean age 53.i f 15.2 years). The mean age for chronic pain patients with major depression was 57.6 f 7.9 years and was significantly different from chronic pain patients without major depression (46.8 f 9.3 years) (x2 = 10.1, df= 66, P < 0.05). The mean age for patients with primary major depression with pain complaints was 55.9 f 12.5 years and was not significantly different from patients with primary major depression without pain complaints (50.2 of 16.9 years). The male/female ratio for chronic pain patients was 27 : 39; major depression was 9:27. Twenty-nine percent of chronic pain patients with major depression showed non-suppression with cortisol following dexamethasone. None of the chronic pain

42 TABLE

I

DST IN RELATION PAIN

TO THE PRESENCE

Diagnosis

OR ABSENCE

OF MAJOR

DST

- DST

Major depression No depression

DEPRESSION

Total

24 34

10 0

IN C‘HRONI(’

---._

?4 34

x’ = 11.72. P < 0.001.

TABLE

I1

DST IN RELATION TO THE PRESENCE MAJOR DEPRESSION

OR ABSENCE

OF PAIN COMPLAINTS

Diagnosis

+ DST

- DST

Total

Pain No pain

10 17

4 I

14 24

IN PRIMARY

Not significant.

patients without major depression showed non-suppression (Table I). In addition, the 5 patients with dysthymic disorder showed suppression. 70.8% of patients with primary major depression without pain complaints and 71.4% with primary major depression with pain complaints showed non-suppression (Table II). Fig. 1 shows a scattergram for the highest post-dexamethasone plasma cortisol levels among the 4 diagnostic groups. Fig. 2 shows the highest mean post-dexamethasone plasma cortisol level among the 4 diagnostic groups. There was a highly significant

Chronic 3Or

Pain

Primary Major Depression .

I

.

.. :

’ 0 Major

No

Depression

Depression

;

:.

I

1

j

Pain

Fig. 1. Scattergram for the highest post-dexamethasone

8 .

No PJIII

plasma cortisol levels among 4 diagnostic

groups.

43 Chronic

Pain (CP)

Primary

Major

Depression

CP

VS PMD

ANOVA,

CPMD

VS CPNoD

Newman-Keuls

CPMP

VS PMDP

ANOVA df=l, F=20.81,

PMDP

VS PMDNoP

not significant

Fig. 2. Highest mean post-dexamethasone

df=l,

(PMD)

F=62.35,

-CO.00001

pCO.05 pCO.00001

plasma cortisol levels.

difference in the highest post-dexamethasone plasma cortisol level between chronic pain patients and those with primary major depression (2.4 f. 2.4 pg/dl versus 10.23 f 7.8 pg/dl, P < 0.00001) (see Fig. 2). Chronic pain patients with major depression differed significantly from chronic pain patients without major depression (3.4 + 3.33 pg/dl versus 1.6 f 0.9 pg/dl, P -c 0.05). Chronic pain patients with major depression also differed from patients with primary major depression with pain complaints (3.4 f 3.3 pg/dl versus 10.7 k 8 pg/dl, P -c 0.0001). Patients having primary major depression with pain complaints do not differ significantly from patients having primary major depression without pain complaints (10.7 f 8.0 pg/dl versus 9.9 + 7.9 pg/dl).

In this study we have shown that chronic pain patients with major depression differ from primary major depression in post-dexamethasone cortisol levels. Further, patients having primary major depression with pain complaints do not differ from those without pain complaints in post-dexamethasone cortisol levels. The lower rate of non-suppression in chronic pain patients with major depression compared to patients with primary major depression may be related to clinical characteristics. We have recently shown some of the clinical characteristics which can identify non-suppression from suppression [ll]. The symptoms that constitute the profile of non-suppression are similar to those described for endogenous depression. The symptom profile includes: depressed mood, reduced appetite, suicidal ideation, loss of libido, hypochondriasis, paranoid symptoms, reduced

44

interest, loss of insight, concentration difficulties. and anxiety. Although WC dni nor assess the symptom profile in these groups of patients using rating scales, it is highI\ likely that the higher incidence of non-suppression in major depression was related to the higher incidence of these symptoms. Further studies should use clinical characteristics in attempting to discriminate between chronic pain patients with major depression from primary major depression alone. The dexamethasone suppression test may be a useful method in discriminating between (1) chronic pain versus primary major depression, (2) chronic pain with major depression versus primary major depression, and (3) chronic pain with major depression versus chronic pain and no depression. Further studies are needed to verify these findings.

References 1 Atkinson, E., Kremer. E.F., Risch, SC. et al., Neuroendocrine function and endogenous opioid peptide systems in chronic pain, Psychosomatics, 24 (1983) 899-913. 2 Carroll, B.J.. Feinberg, M., Greden, J.F. et al., A specific laboratory test for the diagnosis of melancholia, Arch. gen. Psychiat., 38 (1981) 15-22. 3 Diagnostic and Statistical Manual of Mental Disorders. 3rd Edition, Amer. Psychiatric Ass.. New York, 1980. 4 France, R.D., Houpt, J.L., Skott, A. et al., Depression as a psychopathological disorder in chronic low back pain, J. psychosom. Res., 30 (1986) 127-133. 5 France, R.D. and Krishnan, K.R.R., The dexamethasone suppression test as a biological marker of depression in chronic pain, Pain. 21 (1985) 49-55 6 France. R.D., Krishnan, K.R.R., Houpt, J.L. et al., Differentiation of depression from chronic pain using a comparison of DST and diagnostic criteria, Amer. J. Psychiat.. 141 (1984) 1577-1579. 7 Kramlinger, K.G., Swanson, D.W. and Manna, T.. Are patients with chronic pain depressed?, Amer. J. Psychiat., 140 (1983) 747-749. 8 Krishnan, K.R.R.. France, R.D. and Houpt. J.L.. Chronic low back pain and depression, Psychosom. Med., 26 (1985) 299-302. 9 Krishnan, K.R.R.. France, R.D., Pelton, S., McCann, U.D.. Davidson, J. and Urban, B.J., Chronic pain and depression. 1. Classification of depression in chronic low back pain patients. Pain 22 (1985) 279-287. 10 Krishnan, K.R.R., France, R.D.. Pelton, S.. McCann, U.D., Davidson, J. and Urban. B.J., Chrome pain and depression. II. Symptoms of anxiety in chronic low back pain patients and their relationship to subtypes of depression, Pam, 22 (1985) 289-294. 11 Krishnan, K.R.R., France, R.D., Pelton, S. et al.. What does the dexamethasone suppression test identify?, Biol. Psychiat., 20 (1985) 957-964. 12 Large, R.. The psychiatrist and the chronic pain patients: 172 anecdotes, Pain, 9 (1980) 253-263. 13 Merskey, H. and Spear, F.G.. Pam, Psychological and Psychiatric Aspects, Balliere, TindaB and Cassell. London, 1967. C.R. and Bomca, J.J.. Pam. depression and illness behavior in a pain clinic 14 Pilowsky, 1.. Chapman, population, Pain, 4 (1977) 183-192. 15 Romano, J.M. and Turner, J.A., Chronic pain and depression: does the evidence support a relationship?, Psychol. Bull., 19 (1985) 18-34. 16 SyvaJakti, E, Hyyppa, M.T. and Salminen, J.K., Depression and the dexamethasone test (DST) in patients with non-specific somatic complaints, Ann. clin. Res., 17 (1985) 148-151. 17 Von Knorring, L., Penis, C.. E&man, M., Eriksson, V. and Penis, H., Pam as a symptom in depressive disorders. I. Relationship to diagnostic subgroup and depressive symptomatology. Pam, 15 (1980) 19-26.