- Email: [email protected]
Normalization of the dexamethasone suppression test at discharge from hospital
Journal of Affective Elsevier
Disorders, 5 ( 1983) I9 I- 197
191
Normalization of the Dexamethasone Suppression Test at Discharge from Hospital Its Prognostic Boghos The Affective
1. Yerevanian, Halldora Russotto, Patricia Mallon,
Value
Olafsdottir, Evelyne Milanese, John Gloria Baciewicz and Eli Sagi
Disorders Program, Department of Psychiatry, The University of Rochester, Medical Center, Rochester, NY (U.S.A.) (Received 7 October, 1982) (Accepted 6 December, 1982)
Fourteen patients with RDC diagnosis of primary, endogenous, major depressive disorder were studied in an inpatient setting. All were non-suppressors on the Dexamethasone Suppression Test on admission to hospital and were retested at discharge. Over 70% of patients continued to be non-suppressors at discharge, when in clinical remission. Four out of 14 patients converted to normal suppression. All 10 of the non-normalizers did poorly on follow-up: 3 patients committed suicide. All normalizers did well. Non-normalization of the DST at discharge from hospitalization may be more common than previously suspected and predicts poor clinical outcome.
Introduction The Dexamethasone Suppression Test has become a useful tool in the hands of clinicians and researchers in the area of depression. Studies (Stokes et al. 1975; Carroll et al. 1976b; Brown et al. 1979; Schlesser et al. 1979) have shown that an abnormal DST identifies about 40% of patients with endogenous depression with
This study was supported in part by research grant RR-0004 from NIH DHHS. Reprint requests to: B.I. Yerevanian, M.D., Department of Psychiatry, The University Medical Center 300 Crittenden Boulevard, Rochester, NY 14642, U.S.A.
0165-0327/83/$03.00
0 1983 Elsevier Science Publishers
B.V.
of Rochester,
192
close to 95% confidence (Carroll et al. 1981). The diagnostic potential of the test has been discussed in detail by Carroll (Carroll et al. 1980a, b; 1981). The abnormality is presumed to be of central origin, reflecting disinhibition of the hypothalamic-pituitary-adrenal axis (Carroll 1972; Carroll et al. 1976a, b). It has been suggested (Sachar et al. 1975; Carroll et al. 1976b) that the HPA axis abnormality is state-related: with the resolution of the endogenous depressive episode it eventually normalizes. A closer look at the temporal relationship between depressive symptoms and the endocrine abnormality shows that the HPA abnormality (1) may closely parallel the clinical course of the patient (Carroll and Mendels 1976; Dysken et al. 1979; Papakostas et al. (1980), (2) may normalize before clinical recovery (Holsboer et al. 1982) and (3) may persist after remission of clinical symptoms with apparent recovery (Albala et al. 1980; Greden et al. 1980). Greden et al. (1980) in a retrospective study of 14 cases of endogenous depression, reported that persistence of the DST abnormality at discharge from hospital predicted poor outcome, despite apparent clinical recovery. Goldberg (1980) reported on 8 cases of major depression and found that 5 normalizers did not relapse at 2 months follow-up, while 3 non-normalizers relapsed. Holsboer et al. (1982) found in a series of 20 patients. 4 who did not normalize on the DST despite clinical recovery. All 4 eventually relapsed. The present study was conducted to evaluate whether the DST at discharge from hospital predicts relapse and clinical outcome. We prospectively followed up a group of patients who on admission had positive DST and who were retested at discharge. We compared the clinical outcome in patients who normalized on the DST with those who did not normalize.
Patients and Methods All 14 patients in the study were admitted to the Affective Disorders Unit of the University of Rochester Department of Psychiatry. Admitted patients are routinely tested by the DST on admission and discharge if they do not meet the technical and medical exclusion criteria as set by Carroll et al. (1981). Subjects therefore were all consecutive non-suppressors admitted over a period of 6 months, and who were also retested at discharge. The standard evaluation of depressed patients on our Unit consists of the following: (1) a structured interview with the SADS by a member of the research team, (2) unstructured clinical interviews by two interviewers, a senior psychiatrist and the primary therapist (usually a psychiatric resident), (3) a diagnostic interview with family by the clinical social worker trained in the phenomenology of affective disorders, (4) extensive record review by members of the research team, (5) a complete physical examination and a battery of laboratory tests to rule out medical illness, and (6) weekly psychometric evaluation by the use of the 17-item Hamilton Depression Scale (Hamilton 1960), The Beck Depression Inventory (Beck et al. (1976), and the Global Assessment Scale (Spitzer et al. 1977). Members of the Research Team then meet in a diagnostic conference and assign RDC (Spitzer et al.
1
72
41
53
52 64
58 25
37
42 64
75 25 26 63
1
2
3
4 5
6
8
9 10
11 I2 13 14
7
Age (Yr)
FEATURES
Patient
CLINICAL
TABLE PRIMARY,
Bipolar Unipolar Unipolar
+ +
F
M F
_ _ -
Unipolar Bipolar Unipolar Unipolar
Unipolar Unipolar
+
F M
F M M M
Unipolar
+
F
+
Bipolar Unipolar
+ +
M F
+
Unipolar
+
M
Diagnosis
ENDOGENOUS
Unipolar
Discharge DST
WITH
+
M
Sex
OF PATIENTS
ECT Desipramine Nortriptyline ECT
Desipramine ECT
Nortriptyline
Nortriptyline
Lithium and desipramine Desipramine Desipramine
Desipramine
ECT
Treatment
DEPRESSION
DST ON ADMISSION
Readmitted within 2 weeks. RDC - Major depression Readmitted within 3 weeks. RDC - Major depression Continued mildly depressed RDC - Minor depression Suicided Readmitted within 2 weeks. RDC - Major depression Switched into hypomania, then suicided. RDC minor depression. 3-Tricyclic antidepressant changes RDC minor depression. Not back to baseline Suicided RDC major depression - anhedonic, unable to work No RDC diagnosis - Doing very well No RDC diagnosis - Doing very well Back to baseline - Schizoid personality No RDC diagnosis - Doing very well
Outcome
WITH ABNORMAL
194
1977) and clinical diagnosis by consensus. Patients were included in the study if: (1) they met RDC criteria for major depressive disorder, primary and endogenous, and (2) if they were non-suppressors of DST on admission, Secondary depressions as well as schizoaffective depressed patients were excluded from this study. All members of the research team involved in the diagnostic and follow-up process were bfind to the results of both admission and discharge DST. The psychiatrist involved in the follow-up evaluation was blind to the discharge DST. Follow-up evaluation was done by a psychiatrist of the team. Evaluation included patient interviews, family interview where possible, and review of all records available. Patients were then given an RDC diagnosis on follow-up. The length of the follow-up was up to 18 months, The age range of the patients was 25 to 75 years - 8 patients were male and 6 were female. The demographic variables of these patients are summarized in Table 1. The DST
After a drug-free period of 3-10 days, and after informed consent was obtained, patients were given 1 mg dexamethasone p.o. at 11:30 p.m. Plasma cortisol levels were drawn the next day at 4:00 p.m. and 11:OO p.m. Blood was collected in heparinized tubes, the plasma separated immediately and samples stored at - 20°C until assayed. Plasma cortisol was determined by radioimmunoassay. The test was considered abnormal (non-suppressors) if any of the post-dexamethasone cortisol levels were 5 pg/dl or above. Patient treatment was uncontrolled and was decided upon by attending psychiatrists. Treatment included ECT, tricyclic antidepressants, and lithium as summarized in Table 1.
Results The patients were divided into 2 groups based on their DST results at discharge from hospital: (1) normalizers and (2) non-normalizers. Ten out of 14 patients were non-normalizers despite apparent clinical recovery and suitability for discharge which was strictly a clinical decision taken by the attending psychiatrist. Four of 14 patients converted to normal suppression at discharge. The mean age of non-normalizers was 50.8 while the mean age of the normalizers was 47. Two of four of the normalizers were female, while 6 of 10 of the non-normalizers were female. The 2 groups were thus neither different with respect to age or sex, nor as to the admission Hamilton Rating Scale for depression. On discharge the mean Hamilton score for normalizers was 8.5 _+6.13 (SD) while the mean Hamilton for the non-normalizers was 11.1 + 4.6 (SD). The Global Assessment Scale (GAS) at discharge for the normalizers was 70 + 8.16 (SD), while for the non-normalizers the mean GAS was 57.8 + 9.7 (SD). While there was a tendency of the non-normalizers to have higher Hamilton scores and lower GAS at discharge, the
195
difference (two-tailed
was not test)
statistically
significant:
0.1 < P < 0.5 for
HDRS
and
GAS
Outcome measures Of the 10 non-normalizers 2 patients committed suicide within 5 days of discharge DST. One patient developed hypomania, remitted for a brief period on lithium. but after a stormy course of 8 months finally committed suicide. Three patients were readmitted with a diagnosis of major depressive disorder within 3 weeks of discharge. Two had a positive DST on readmission, one had a negative DST. Patients number 8 and 10 continued to meet RDC criteria for minor depression at 2 and 4 months follow-up, respectively, and are working only part-time in their respective jobs. Both have required 2 antidepressant changes despite adequate levels and doses. Patient number 3 denies feeling depressed, however, has returned to part-time work and, on follow-up psychological evaluation, evidenced clear-cut depression and according to the patient’s husband, she is not back to baseline functioning. Of the normalizers, 3 out of 4 patients are doing extremely well, do not meet RDC diagnosis, and are back to their baseline functioning. Patient number 14 recovered from his major depression, and returned to his baseline characterological depression of 10 years duration. Thus, all 10 patients who did not normalize have not completely recovered and have not returned to baseline functioning at 2-8 months follow-up; whereas all 4 normalizers were doing well with no recurrence of their symptoms of major depression.
Discussion The results reported in this study confirm earlier reports (Greden et al. 1980; Holsboer at al. 1982) indicating that a persistently abnormal DST at discharge from hospital predicts poor clinical outcome. This study also agrees with the Greden study in that the non-normalizer groups tends to be sicker as evidenced by the higher Hamilton Depression Scores as well as the Global Assessment Scales compared to the normalizers. It should be pointed out, however, that 4 of the non-normalizers had discharge Hamilton scores of 8 and below and 9 were below 14. Since normalizers and non-normalizers did not differ with respect to age, sex, and severity of depression on admission, and were diagnostically homogenous, one of the critical factors that predicted outcome seems to have been the persistence of the HPA abnormality. It was striking to us that 10 out of 14 patients discharged from the hospital (71%) continued to have abnormal DST. The mean length of stay of our population was 23.7 + 6.8 (standard deviation) days. The findings of this study reflecting a large proportion of patients still biochemically nonrecovered and at risk for relapse suggest that although of primary importance, the clinical features alone may not be sufficient to define complete recovery from a depressive episode. The Dexametha-
196
sane Suppression Test may thus be an important factor to be considered in the clinical decision-making for discharge hospitalization. Of interest was the fact that early discharge not only predicts continued morbidity but also mortality by suicide. Three of our patients suicided: 1 at 8 month follow-up, and 2 within 3 days of discharge. The last 2 patients were clinically remitted on discharge and were considered to have characterological disturbances, one with passive-dependent traits and the other with mixed and explosive features. The concept of characterologically-based depressions is quite unclear in the literature and needs further characterization in its relationship to Major Depressive Disorder (Yerevanian and Akiskal 1979). In both of these patients, the possibility of the patient’s lifelong “characterological disturbances” being a manifestation of underlying affective disorder was specifically raised during the clinical management of these patients. We believe that had we not been blind to the DST results, we would have been alerted to the potential for catastrophe in these 2 patients. The Dexamethasone Suppression Test thus may be a probe into the biological substrate of this group of characterological depressions, a subgroup which we have termed “true dysthymia” (Yerevanian and Akiskal 1979). An association between suicidal behavior and HPA-axis hyperactivity has been described by several authors (Levy and Hansen 1969; Krieger 1970; Traskman et al. 1980). Bunney et al. (1969) noted an association between serious suicidal behavior and increased urinary 17-hydroxycorticosteroids. Coryell and Schlesser (1981) studied 243 inpatients with unipolar depression. Four patients who later committed suicide were among those who had abnormal DST results. One of four non-normalizers in the Greden study committed suicide at 2-months follow-up. More recently the question has been raised whether the Dexamethasone Suppression Test itself can activate suicidal potential (Asberg et al. 198 1; Beck-Friis et al. (198 1). Coryell (1982) and Kronfol et al. (1982) looked carefully into the issue and found no reason to suspect a causal relationship between administration of dexamethasone and suicidal behavior. Even though 2 of the suicides occured within 5 days of the DST, we have no reason to suspect that 1 mg of dexamethasone was contributory to the suicides. Conclusion
DST at discharge from hospitalization is useful predictor of post-discharge clinical course. Continued non-suppression predicts poor outcome. In addition, persistent abnormalities following clinical remission might be more common than previously suspected as evidenced by the fact that over 70% of patients who were positive on admission continue to be positive at discharge in our series. References Albala, A.A. and @eden, J.F., Serial dexamethasone suppression tests in affective disorders, Amer. J. Psychiat., 137 (1980) 383. &berg, M.. Varpila-Hannsson, R., Tomba, P., Aminoff, A.-K., M&rtensson, B., Thor&n, P., TraskmanBendz, L., Eneroth, P. and Astram, G., (Letter to the Editor), Amer. J. Psychiat., 138 (1981) 994-995.
197
Beck. A.T., Ward, C.H. et al., An inventory for measuring depression, Arch. Gen. Psychiat., 4 (1976) 561. Beck-Friis, J., Aperia, B., Kjellman, B., Ljunggren, J.-G., Petterson, U., Sara, V., Sjolin, A., Unden, F. and Wetterberg, L., Suicidal behavior and the Dexamethasone Suppression Test (Letter to the Editor), Amer. J. Psychiat., 138 (1981) 993-994. Brown, W.A. and Shuey, I., Response to dexamethasone and subtype of depression, Arch. Gen. Psychiat.. 37 (I 980) 747-75 1. Brown, W.A. and Johnston, R. and Mayfield, D., The 24-hour dexamethasone suppression test in a clinical setting - Relationship to diagnosis, symptoms and response to treatment. Amer. J. Psychiat., 136 (1979) 543-547. Bunney, W.E., Fawcett, J.A., Davis, J.M. et al., Further evaluation of urinary 17-hydrocorticosteroids in suicidal patients, Arch. Gen. Psychiat., 21 (1969) 415-418. Carroll, B.J., The hypothalamic-pituitary-adrenal axis in depression. In: B. Davies, B.J. Carroll and R.M. Mowbray (Eds.), Depressive Illness - Some Research Studies, Thomas, Springfield, IL. 1972, pp. 23-201. Carroll, B.J. and Mendels, J.. Neuroendocrine regulation in affective disorders. In: E.J. Sachar (Ed.), Hormones, Behavior, and Psychopathology, Raven Press, New York, NY, 1976. pp. 193-224. Carroll, B.J., Martin, F.J.R. and Davies, B.M., Resistance to suppression by dexamethasone of plasma 1 I-OHCS levels in severe depressive illness, Brit. Med. J., III (1968) 285-287. Carroll, B.J., Curtis, G.C. and Mendels, J., Neuroendocrine regulation in depression, Part 1 (Limbic-systern adrenocortical dysfunction), Arch. Gen. Psychiat., 33 (1976a) 1039- 1044. Carroll, B.J., Curtis, G.C. and Mendels, J., Neuroendocrine regulation in depression. Part 2 (Discrimination of depressed from nondepressed patients), Arch. Gen. Psychiat., 33 (1976b) 105 1- 1057. Carroll, B.J., Feinberg, M., Greden, J.F. et al., Diagnosis of endogenous depression - Comparison of clinical, research and neuroendocrine criteria, J. Affect. Dis., 2 (1980a)177- 194. Carroll, B.J., Greden, J.F. and Feinberg, M., Neuroendocrine disturbances and the diagnosis and aetiology of endogenous depression, Lancet, i (1980b) 32 l-322. Carroll, B.J., Feinberg, M., Greden, J.F., Tarika, J., Albala, A.A., Haskett, R.F., Norman, McL. J., Kronfol, Z., Lohr, N., Steiner, M., DeVigne, J.P. and Young, E., A specific laboratory test for the diagnosis of melancholia - Standardization, validation and clinical utility, Arch Gen. Psychiat., 38 (1981) 15-22. Coryell, W., Suicidal behavior and the Dexamethasone Suppression Test - Lack of association, Amer. J. Psychiat., 139 (1982) 9. Coryell, W. and Schlesser, M.A., Suicide and the dexamethasone suppression test in unipolar depression, Amer. J. Psychiat., 138 (1981) 1120-1121. Dysken, M.W., Pandey, G.H., Chang, S.S., Hicks, R. and Davis, J.M., Serial post-dexamethasone cortisol levels in a patient undergoing ECT, Amer. J. Psychiat., 136 (1979) 1328- 1329. Goldberg, I.K., Dexamethasone suppression test as indicator of safe withdrawal of antidepressant therapy, Lancet, i (1980) 376. Greden, J.J., Albala, A.A., Haskett, R.F., Norman, McL. J., Goodman, L., Steiner, M. and Carroll, B.J., Normalization of dexamethasone suppression test - A laboratory index of recovery from endogenous depression, Biol. Psychiat., 15 (1980) 4499458. Hamilton, M., A rating scale for depression, J. Neural. Neurosurg. Psychiat., 23 (1960) 56-62. Holsboer, F., Liebl, R. and Hofschuster, E., Repeated dexamethasone suppression test during depressive illness, J. Affect. Dis., 4 (1982) 93- 10 1. Krieger, G., Biochemical predictors of suicide, Dis. Nerv. Syst., 3 1 (1970) 478482. Kronfol, Z., Greden, J.F.. Gardner, R. and Carroll, B.J., (Letter to the Editor), Amer. J. Psychiat., 139 (1982) 9. Levy, B. and Hansen, E., Failure of the urinary test for suicide potential, Arch. Gen. Psychiat., 20 (1969) 415-41s. Papakostas, Y., Lee, J., Johnson, L. and Fink, M., Neuroendocrine effects of ECT. In: Scientific Proceedings of Society of Biological Psychiatry, Abstract No. 3 (1980) p. 35. Sachar, E.J., Hellman, L., Roffward, H.P. et al., Disrupted 24-hour patterns of cortisol secretion in psychotic depression, Arch. Gen. Psychiat., 28 (1975) 19-24. Schlesser, M.A., Winokur, G. and Sherman, B.M., Hypothalmic-pituitary-adrenal axis activity in depressive illness - Its relationship to classification, Arch. Gen. Psychiat., 37 (1980) 737-743.
Disorders, 5 ( 1983) I9 I- 197
191
Normalization of the Dexamethasone Suppression Test at Discharge from Hospital Its Prognostic Boghos The Affective
1. Yerevanian, Halldora Russotto, Patricia Mallon,
Value
Olafsdottir, Evelyne Milanese, John Gloria Baciewicz and Eli Sagi
Disorders Program, Department of Psychiatry, The University of Rochester, Medical Center, Rochester, NY (U.S.A.) (Received 7 October, 1982) (Accepted 6 December, 1982)
Fourteen patients with RDC diagnosis of primary, endogenous, major depressive disorder were studied in an inpatient setting. All were non-suppressors on the Dexamethasone Suppression Test on admission to hospital and were retested at discharge. Over 70% of patients continued to be non-suppressors at discharge, when in clinical remission. Four out of 14 patients converted to normal suppression. All 10 of the non-normalizers did poorly on follow-up: 3 patients committed suicide. All normalizers did well. Non-normalization of the DST at discharge from hospitalization may be more common than previously suspected and predicts poor clinical outcome.
Introduction The Dexamethasone Suppression Test has become a useful tool in the hands of clinicians and researchers in the area of depression. Studies (Stokes et al. 1975; Carroll et al. 1976b; Brown et al. 1979; Schlesser et al. 1979) have shown that an abnormal DST identifies about 40% of patients with endogenous depression with
This study was supported in part by research grant RR-0004 from NIH DHHS. Reprint requests to: B.I. Yerevanian, M.D., Department of Psychiatry, The University Medical Center 300 Crittenden Boulevard, Rochester, NY 14642, U.S.A.
0165-0327/83/$03.00
0 1983 Elsevier Science Publishers
B.V.
of Rochester,
192
close to 95% confidence (Carroll et al. 1981). The diagnostic potential of the test has been discussed in detail by Carroll (Carroll et al. 1980a, b; 1981). The abnormality is presumed to be of central origin, reflecting disinhibition of the hypothalamic-pituitary-adrenal axis (Carroll 1972; Carroll et al. 1976a, b). It has been suggested (Sachar et al. 1975; Carroll et al. 1976b) that the HPA axis abnormality is state-related: with the resolution of the endogenous depressive episode it eventually normalizes. A closer look at the temporal relationship between depressive symptoms and the endocrine abnormality shows that the HPA abnormality (1) may closely parallel the clinical course of the patient (Carroll and Mendels 1976; Dysken et al. 1979; Papakostas et al. (1980), (2) may normalize before clinical recovery (Holsboer et al. 1982) and (3) may persist after remission of clinical symptoms with apparent recovery (Albala et al. 1980; Greden et al. 1980). Greden et al. (1980) in a retrospective study of 14 cases of endogenous depression, reported that persistence of the DST abnormality at discharge from hospital predicted poor outcome, despite apparent clinical recovery. Goldberg (1980) reported on 8 cases of major depression and found that 5 normalizers did not relapse at 2 months follow-up, while 3 non-normalizers relapsed. Holsboer et al. (1982) found in a series of 20 patients. 4 who did not normalize on the DST despite clinical recovery. All 4 eventually relapsed. The present study was conducted to evaluate whether the DST at discharge from hospital predicts relapse and clinical outcome. We prospectively followed up a group of patients who on admission had positive DST and who were retested at discharge. We compared the clinical outcome in patients who normalized on the DST with those who did not normalize.
Patients and Methods All 14 patients in the study were admitted to the Affective Disorders Unit of the University of Rochester Department of Psychiatry. Admitted patients are routinely tested by the DST on admission and discharge if they do not meet the technical and medical exclusion criteria as set by Carroll et al. (1981). Subjects therefore were all consecutive non-suppressors admitted over a period of 6 months, and who were also retested at discharge. The standard evaluation of depressed patients on our Unit consists of the following: (1) a structured interview with the SADS by a member of the research team, (2) unstructured clinical interviews by two interviewers, a senior psychiatrist and the primary therapist (usually a psychiatric resident), (3) a diagnostic interview with family by the clinical social worker trained in the phenomenology of affective disorders, (4) extensive record review by members of the research team, (5) a complete physical examination and a battery of laboratory tests to rule out medical illness, and (6) weekly psychometric evaluation by the use of the 17-item Hamilton Depression Scale (Hamilton 1960), The Beck Depression Inventory (Beck et al. (1976), and the Global Assessment Scale (Spitzer et al. 1977). Members of the Research Team then meet in a diagnostic conference and assign RDC (Spitzer et al.
1
72
41
53
52 64
58 25
37
42 64
75 25 26 63
1
2
3
4 5
6
8
9 10
11 I2 13 14
7
Age (Yr)
FEATURES
Patient
CLINICAL
TABLE PRIMARY,
Bipolar Unipolar Unipolar
+ +
F
M F
_ _ -
Unipolar Bipolar Unipolar Unipolar
Unipolar Unipolar
+
F M
F M M M
Unipolar
+
F
+
Bipolar Unipolar
+ +
M F
+
Unipolar
+
M
Diagnosis
ENDOGENOUS
Unipolar
Discharge DST
WITH
+
M
Sex
OF PATIENTS
ECT Desipramine Nortriptyline ECT
Desipramine ECT
Nortriptyline
Nortriptyline
Lithium and desipramine Desipramine Desipramine
Desipramine
ECT
Treatment
DEPRESSION
DST ON ADMISSION
Readmitted within 2 weeks. RDC - Major depression Readmitted within 3 weeks. RDC - Major depression Continued mildly depressed RDC - Minor depression Suicided Readmitted within 2 weeks. RDC - Major depression Switched into hypomania, then suicided. RDC minor depression. 3-Tricyclic antidepressant changes RDC minor depression. Not back to baseline Suicided RDC major depression - anhedonic, unable to work No RDC diagnosis - Doing very well No RDC diagnosis - Doing very well Back to baseline - Schizoid personality No RDC diagnosis - Doing very well
Outcome
WITH ABNORMAL
194
1977) and clinical diagnosis by consensus. Patients were included in the study if: (1) they met RDC criteria for major depressive disorder, primary and endogenous, and (2) if they were non-suppressors of DST on admission, Secondary depressions as well as schizoaffective depressed patients were excluded from this study. All members of the research team involved in the diagnostic and follow-up process were bfind to the results of both admission and discharge DST. The psychiatrist involved in the follow-up evaluation was blind to the discharge DST. Follow-up evaluation was done by a psychiatrist of the team. Evaluation included patient interviews, family interview where possible, and review of all records available. Patients were then given an RDC diagnosis on follow-up. The length of the follow-up was up to 18 months, The age range of the patients was 25 to 75 years - 8 patients were male and 6 were female. The demographic variables of these patients are summarized in Table 1. The DST
After a drug-free period of 3-10 days, and after informed consent was obtained, patients were given 1 mg dexamethasone p.o. at 11:30 p.m. Plasma cortisol levels were drawn the next day at 4:00 p.m. and 11:OO p.m. Blood was collected in heparinized tubes, the plasma separated immediately and samples stored at - 20°C until assayed. Plasma cortisol was determined by radioimmunoassay. The test was considered abnormal (non-suppressors) if any of the post-dexamethasone cortisol levels were 5 pg/dl or above. Patient treatment was uncontrolled and was decided upon by attending psychiatrists. Treatment included ECT, tricyclic antidepressants, and lithium as summarized in Table 1.
Results The patients were divided into 2 groups based on their DST results at discharge from hospital: (1) normalizers and (2) non-normalizers. Ten out of 14 patients were non-normalizers despite apparent clinical recovery and suitability for discharge which was strictly a clinical decision taken by the attending psychiatrist. Four of 14 patients converted to normal suppression at discharge. The mean age of non-normalizers was 50.8 while the mean age of the normalizers was 47. Two of four of the normalizers were female, while 6 of 10 of the non-normalizers were female. The 2 groups were thus neither different with respect to age or sex, nor as to the admission Hamilton Rating Scale for depression. On discharge the mean Hamilton score for normalizers was 8.5 _+6.13 (SD) while the mean Hamilton for the non-normalizers was 11.1 + 4.6 (SD). The Global Assessment Scale (GAS) at discharge for the normalizers was 70 + 8.16 (SD), while for the non-normalizers the mean GAS was 57.8 + 9.7 (SD). While there was a tendency of the non-normalizers to have higher Hamilton scores and lower GAS at discharge, the
195
difference (two-tailed
was not test)
statistically
significant:
0.1 < P < 0.5 for
HDRS
and
GAS
Outcome measures Of the 10 non-normalizers 2 patients committed suicide within 5 days of discharge DST. One patient developed hypomania, remitted for a brief period on lithium. but after a stormy course of 8 months finally committed suicide. Three patients were readmitted with a diagnosis of major depressive disorder within 3 weeks of discharge. Two had a positive DST on readmission, one had a negative DST. Patients number 8 and 10 continued to meet RDC criteria for minor depression at 2 and 4 months follow-up, respectively, and are working only part-time in their respective jobs. Both have required 2 antidepressant changes despite adequate levels and doses. Patient number 3 denies feeling depressed, however, has returned to part-time work and, on follow-up psychological evaluation, evidenced clear-cut depression and according to the patient’s husband, she is not back to baseline functioning. Of the normalizers, 3 out of 4 patients are doing extremely well, do not meet RDC diagnosis, and are back to their baseline functioning. Patient number 14 recovered from his major depression, and returned to his baseline characterological depression of 10 years duration. Thus, all 10 patients who did not normalize have not completely recovered and have not returned to baseline functioning at 2-8 months follow-up; whereas all 4 normalizers were doing well with no recurrence of their symptoms of major depression.
Discussion The results reported in this study confirm earlier reports (Greden et al. 1980; Holsboer at al. 1982) indicating that a persistently abnormal DST at discharge from hospital predicts poor clinical outcome. This study also agrees with the Greden study in that the non-normalizer groups tends to be sicker as evidenced by the higher Hamilton Depression Scores as well as the Global Assessment Scales compared to the normalizers. It should be pointed out, however, that 4 of the non-normalizers had discharge Hamilton scores of 8 and below and 9 were below 14. Since normalizers and non-normalizers did not differ with respect to age, sex, and severity of depression on admission, and were diagnostically homogenous, one of the critical factors that predicted outcome seems to have been the persistence of the HPA abnormality. It was striking to us that 10 out of 14 patients discharged from the hospital (71%) continued to have abnormal DST. The mean length of stay of our population was 23.7 + 6.8 (standard deviation) days. The findings of this study reflecting a large proportion of patients still biochemically nonrecovered and at risk for relapse suggest that although of primary importance, the clinical features alone may not be sufficient to define complete recovery from a depressive episode. The Dexametha-
196
sane Suppression Test may thus be an important factor to be considered in the clinical decision-making for discharge hospitalization. Of interest was the fact that early discharge not only predicts continued morbidity but also mortality by suicide. Three of our patients suicided: 1 at 8 month follow-up, and 2 within 3 days of discharge. The last 2 patients were clinically remitted on discharge and were considered to have characterological disturbances, one with passive-dependent traits and the other with mixed and explosive features. The concept of characterologically-based depressions is quite unclear in the literature and needs further characterization in its relationship to Major Depressive Disorder (Yerevanian and Akiskal 1979). In both of these patients, the possibility of the patient’s lifelong “characterological disturbances” being a manifestation of underlying affective disorder was specifically raised during the clinical management of these patients. We believe that had we not been blind to the DST results, we would have been alerted to the potential for catastrophe in these 2 patients. The Dexamethasone Suppression Test thus may be a probe into the biological substrate of this group of characterological depressions, a subgroup which we have termed “true dysthymia” (Yerevanian and Akiskal 1979). An association between suicidal behavior and HPA-axis hyperactivity has been described by several authors (Levy and Hansen 1969; Krieger 1970; Traskman et al. 1980). Bunney et al. (1969) noted an association between serious suicidal behavior and increased urinary 17-hydroxycorticosteroids. Coryell and Schlesser (1981) studied 243 inpatients with unipolar depression. Four patients who later committed suicide were among those who had abnormal DST results. One of four non-normalizers in the Greden study committed suicide at 2-months follow-up. More recently the question has been raised whether the Dexamethasone Suppression Test itself can activate suicidal potential (Asberg et al. 198 1; Beck-Friis et al. (198 1). Coryell (1982) and Kronfol et al. (1982) looked carefully into the issue and found no reason to suspect a causal relationship between administration of dexamethasone and suicidal behavior. Even though 2 of the suicides occured within 5 days of the DST, we have no reason to suspect that 1 mg of dexamethasone was contributory to the suicides. Conclusion
DST at discharge from hospitalization is useful predictor of post-discharge clinical course. Continued non-suppression predicts poor outcome. In addition, persistent abnormalities following clinical remission might be more common than previously suspected as evidenced by the fact that over 70% of patients who were positive on admission continue to be positive at discharge in our series. References Albala, A.A. and @eden, J.F., Serial dexamethasone suppression tests in affective disorders, Amer. J. Psychiat., 137 (1980) 383. &berg, M.. Varpila-Hannsson, R., Tomba, P., Aminoff, A.-K., M&rtensson, B., Thor&n, P., TraskmanBendz, L., Eneroth, P. and Astram, G., (Letter to the Editor), Amer. J. Psychiat., 138 (1981) 994-995.
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