Dexamethasone Suppression Test as a Predictor of Response to Electroconvulsive Therapy. I. Inpatient Treatment

Thirty-eight psychiatric inpatients who fulfilled DSM-III criteria for major depressive disorder with melancholia received weekly dexamethasone suppression tests (DSTs) while undergoing a clinical course of ECT. Blind ratings of clinical improvement were obtained weekly from patients on the Beck Depression Inventory and from physicians and nurses on the Hamilton Depression Scale. The 26 patients with abnormal DSTs and the 12 patients with normal DSTs demonstrated an equivalent rate of clinical remission (75 vs. 77%) as defined by a composite rating of the nurse, physician, and patient. Other individual rater analyses also confirmed the finding that initial DST status is not predictive of response to a course of ECT.     

Melatonin, cortisol and ACTH in patients with major depressive disorder and healthy humans with special reference to the outcome of the dexamethasone suppression test

The 24 hr profiles of melatonin and cortisol in serum, morning levels of ACTH in plasma, and the dexamethasone suppression test (DST) were investigated in 32 acutely ill patients with a RDC diagnosis of major depressive disorder, 24 patients with a history of longlasting unipolar or bipolar major depressive disorder studied in remission, and 33 healthy subjects. A significant decrease in maximum nocturnal melatonin level (MTmax) was found in the acutely ill depressed patients with abnormal DST compared to both those with normal DSTs and the healthy subjects. The MTmax levels were unaltered when these patients were reinvestigated in remission. A decrease of MTmax was also seen in the group of unipolar and bipolar patients studied in remission. Low nocturnal melatonin is proposed to be a trait marker for major depressive disorder and depressive states with abnormalities in the hypothalamic--pituitary--adrenal (HPA) axis. A significant decrease of ACTH levels at 0800 hr after dexamethasone administration the preceding evening was found in the healthy subjects, the unipolar--bipolar patients in remission, and the acutely ill depressed patients with normal DSTs, but was not found in the acutely ill depressed patients with abnormal DSTs. These findings support the hypothesis that pituitary ACTH regulation is altered in depressed patients with abnormal DST. Morning plasma ACTH before the administration of dexamethasone did not significantly differ between the acutely ill depressed patients with abnormal DSTs, normal DSTs, the patients with unipolar--bipolar disease in remission, or the healthy subjects. Thus, the abnormalities in the HPA axis in depresséd patients are proposed to be due to a hypersecretion of corticotrophin releasing factor (CRF) with a subsequent stimulus-induced pituitary desensitization. A significant decrease of melatonin after dexamethasone was seen at 0800 hr in the unipolar--bipolar patients in remission as well as in the healthy subjects, at 1600 hr and 2200 hr in the acutely ill depressed patients in remission, but not at 0800 hr in the acutely ill depressed patients in relapse. A significant regression was found between MTmax levels and the degree of non-suppression of cortisol at 0800 hr in the DST in the acutely ill depressed patients both in relapse and in remission. Melatonin thus is proposed to be an inhibiting factor for CRF during depression. A trend to a phase-advance of cortisol nadir and melatonin peak was seen in the acutely ill depressed patients with abnormal DST, possibly indicating an involvement of the suprachiasmatic nuclei in the hypothalamus.     

Dexamethasone suppression tests in antidepressant treatment of melancholia. The process of normalization and test-retest reproducibility

Pilot studies suggest that changes in response to the dexamethasone suppression test (DST) in melancholic patients receiving antidepressants might represent a laboratory marker of clinical progress. We performed weekly DSTs in 31 hospitalized patients with major depressive disorder, primary and endogenous subtypes, during drug-free and subsequent treatment periods. Most nonsuppressors had progressive normalization of DST responses in conjunction with clinical improvement, DST normalization usually preceded or coincided with good clinical response, and failure to normalize was often associated with poorer clinical outcome. Occasional patients with baseline dexamethasone suppression become nonsuppressive after withdrawal from medication, but the DST has no apparent value as a serial marker in patients with well-documented normal DST findings. Our results extend the construct validity of the DST as a state-related marker in nonsuppressors and suggest future clinical applications.     

Serial dexamethasone suppression tests in psychiatric illness: Part II. A study in major depressive disorder

Weekly dexamethasone suppression tests (DSTs) were performed in 35 patients with major depressive disorder until clinical response. At initial evaluation, 65% of the patients showed nonsuppression, and 85.7% showed nonsuppression at least once during the treatment period. Normalization of the DST results usually coincided with or occurred before clinical recovery, although isolated "peaks" of DST nonsuppression occurred in 45.7% of the patients, irrespective of the clinical course. The test was not useful as a predictor of clinical recovery or relapse. Moderately ill depressed patients had significantly higher nonsuppression rates than schizophrenic or manic patients with corresponding severity scores, indicating that different factors might be associated with nonsuppression in different diagnoses. However, many abnormal DST results could neither be related to the course of the depression nor to the severity of illness; thus other factors must also be responsible for DST nonsuppression.     

Dexamethasone suppression test in hospitalized depressed patients with borderline personality disorder

There is considerable disagreement about the relationship between borderline personality disorder and the affective disorders. The authors report the results of a study of the relationship between dexamethasone suppression and depressive subtype in hospitalized depressed borderline patients. Twenty-three patients met research criteria for unipolar major depressive episode without psychosis of at least moderate severity. Thirteen patients also met criteria for borderline personality disorder. Dexamethasone suppression test (DST) results showed no significant correlation with either melancholia or borderline personality disorder alone. However, of the 13 borderlines, eight failed to suppress and six of those eight were not melancholic. The authors conclude that abnormal response to dexamethasone in nonmelancholic borderlines casts some doubt on the specificity of the DST for melancholia.     

Abnormal escape from dexamethasone suppression in agoraphobia with panic attacks

Patients who met DSM-III criteria for agoraphobia with panic attacks underwent dexamethasone suppression tests (DSTs) before, during, and after treatment with alprazolam or placebo. Similarly, outpatients with major depression were given multiple DSTs as they participated in a study of desmethylimipramine efficacy. The likelihood of an abnormal escape from dexamethasone was similar in the two diagnostic groups; nonsuppression was somewhat more likely among patients with primary depression, but comparisons with agoraphobic groups remained statistically insignificant. These results apparently did not reflect misclassification of primary depression patients as agoraphobics since a history of major depression was not related to the likelihood of nonsuppression within that group. Moreover, change in DST results during treatment reflected clinical change among agoraphobics. After a review of relevant followup and family studies, we conclude that panic disorder and primary depression are separate illnesses and that hypothalamic-pituitary-adrenal axis hyperactivity is an epiphenomenon of both.     

The dexamethasone suppression test in demented outpatients with and without depression

The dexamethasone suppression test (DST) was given to 33 elderly, male outpatients, previously diagnosed by DSM-III criteria as having dementia. Fifteen of these patients also had signs and symptoms of depression and, except for the presence of organic mental syndrome, would have met DSM-III criteria for major depressive episode. Of these 15 depressed, demented patients, 40% had abnormal DST results. None of the 18 patients who had dementia alone had abnormal DSTs. Our data suggest that in elderly, demented outpatients, an abnormal DST may be associated with concomitant depression.     

Dexamethasone suppression in depressed elderly outpatients

The dexamethasone suppression test (DST) was performed as part of the preliminary workup in 85 previously untreated outpatients with major affective disorder, unipolar depressive type, who were over age 60. All patients were given a systematic structured interview (NIMH-DIS), and all had scores over 20 on the 21-item Hamilton Depression Rating Scale (HAM-D). Only 12 patients (14%) had positive DSTs; more of the non-melancholic (6 of 25; 24%) than melancholic (6 of 60; 10%) patients failed to suppress serum cortisol following standard dexamethasone challenge (p less than .10). DST results did not correlate with patients' HAM-D or Zung depression scores, gender, response to treatment, or any other variable studied. These findings suggest that, in comparison to previous reports, a positive DST may be 1) less common in major depressive disorders, 2) no more common in more severely depressed patients, and 3) less relevant to indications for specific treatment.     

The dexamethasone suppression test in depressed and non-depressed geriatric medical inpatients

The frequency of an abnormal response to the dexamethasone suppression test (DST) was examined in 38 geriatric patients hospitalized for medical illnesses and affected by depressive disorders diagnosed according to the DSM III, and in 18 medical patients (used as controls) hospitalized in the same ward. Only 11% of the controls and 11% of those affected by dysthymic disorder had an abnormal DST vs 73% of the patients with major depressive disorder (MDD). The sensitivity of the DST for MDD, in this particular setting, was found to be about 73% and the specificity 89%. The importance of this clinical adjunct in diagnosing the severe depressive disorders is discussed.     

Adrenocortical function and suicidal behavior in depressive disorders

In order to examine the hypothesis that abnormal adrenocortical function is associated with suicidal behavior, morning and afternoon plasma cortisols and 1-mg dexamethasone suppression tests (DSTs) were performed in 65 patients with primary major depressive disorder. Patients with recent suicide attempts (within 28 days before DST) were compared to patients who had made past attempts and those who had never made suicide attempts with respect to age, gender, severity of depression, and plasma cortisol levels. Plasma cortisol levels did not differ significantly among the three groups. Nonsuppression on the DST was associated with presence of delusions, increasing age, and global severity of depression, but not with suicide attempts.     

The hypothalamic-pituitary-adrenal system in panic disorder

The authors evaluated 24 outpatients with panic disorder by means of the afternoon continuous test for cortisol and the 1-mg dexamethasone suppression test (DST) and compared the results with those of 38 outpatients with major depressive disorder and 61 healthy control subjects. The mean basal cortisol level of the patients with panic disorder was significantly higher than that of the normal control subjects but almost identical to that of the depressed patients. Only three of the patients with panic disorder had abnormal DST results. These results indicate that patients with panic disorder have an abnormality of at least one function of the hypothalamic-pituitary-adrenal system which overlaps the abnormality in major depressive disorder.     

The dexamethasone suppression test in elderly, non-depressed patients with dementia

Attempts have been made to use the dexamethasone suppression test (DST) to distinguish patients who have a primary depressive disorder from those suffering a degenerative cerebral disorder. It has been suggested however, that organic brain damage reduces neuroendocrine sensitivity and can be associated with failure to suppress on the DST. This study investigates the DST in 21 patients, over 65 years, with dementia but no evidence of depression on a variety of clinical criteria. Seven patients had abnormal DSTs.     

Neuroendocrine interrelationships in major depressive disorder

The authors administered the thyrotropin-releasing hormone (TRH) stimulation test and the dexamethasone suppression test (DST) to 54 patients who met DSM-III criteria for major depressive disorder and to 19 nondepressed patients. A blunted thyrotropin (TSH) response to TRH injection was noted in 18 depressed patients (33%) but in no nondepressed patients. An escape from dexamethasone suppression was noted in 23 depressed patients (43%) but in only 2 nondepressed patients (11%). The combined sensitivity of the DST and the TRH test in identifying major depressive disorder was 67% with 92% specificity. Only 6 depressed patients (11%) had abnormal responses to both the DST and the TRH test, suggesting that the hypothalamic-pituitary-adrenal axis dysregulation and hypothalamic-pituitary-thyroid axis dysregulation are independent phenomena. These findings support the combined use of these neuroendocrine tests in clinical practice.     

Serial dexamethasone suppression test results during antidepressant therapy: Relationship to diagnosis and clinical change

Thirty-two outpatients with major depression of mild to moderate severity were given a 1 mg dexamethasone test (DST) after 1 week of placebo. Those who failed to show a response to placebo began a 6-week course of desipramine treatment. Severity ratings and the DST were repeated during biweekly visits. DST results robustly validated Winokur's familial subtyping and the primary/secondary distinction only when multiple results were considered. The use of multiple DSTs doubled the sensitivity of this test to primary depression and to familal pure depressive disorder without affecting specificity. Based on these data, a single abnormal DST result is considerably more meaningful than a single normal one. This finding may have particular importance to outpatients.     

Hyperactivity of the hypothalamic-pituitary-adrenal axis and mortality in major depressive disorder

Convergent evidence indicates that HPA-axis hyperactivity is a risk factor for suicide in major depressive disorder, and seven independent reports have shown that patients with abnormal dexamethasone suppression test (DST) results have significantly higher rates of eventual suicide. The identification of interactions between DST results and other clinical predictors would enhance risk assessment, but modest sample sizes have limited such analyses in earlier cohorts. Subjects with major depressive disorder who participated in research protocols at the University of Michigan between 1980 and 1991, who had fully structured diagnostic interviews, and who underwent a 1-mg DST while actively depressed were screened with the National Death Index for a mean (S.D.) follow-up period of 18.0 (5.5) years. Of 334 subjects, 69 (20.7%) were identified as having died. Of these, 13 (18.8%) had died by suicide and 32 (46.4%) from cardiovascular causes. Baseline DST results did not significantly predict death from suicide or from cardiovascular disease for the sample as a whole. Significant relationships between DST results and later suicide did exist for inpatients, for patients with manifest suicidality and, in particular, for inpatients with manifest suicidality. Because nearly all previous reports of DST results and suicide described depressed inpatients, it is possible that the DST is a useful predictor only within this population.     

Choice of antidepressant based on the dexamethasone suppression test

This retrospective analysis of patients with major depressive disorder correlated response to the dexamethasone suppression test (DST) with clinical response to antidepressants. Nonsuppression on the DST predicted good response to noradrenergic drugs; suppression predicted good response to serotonergic drugs.     

Brain purinergic activity linked with depressive symptomatology: hypoxanthine and xanthine in CSF of patients with major depressive disorders

In the course of several studies of hypothalamic-pituitary-adrenal axis activity in depression, 43 patients presented on separate admissions with definite depression and, on both admissions, received dexamethasone suppression tests (DSTs). DST results were discordant across admissions in 21% of cases; among patients who were nonsuppressors on either admission, results were discordant in 40.9%. The correlation between postdexamethasone values obtained on two admissions was highly significant, however. Distinctions between bipolar and unipolar depression and between primary and secondary depression by rates of nonsuppression were inconsistently significant across admissions but were clearer when results from both admissions were pooled and patients with an abnormal DST on either admission were considered nonsuppressors. While abnormal escape from dexamethasone suppression occurs in a significant proportion of depressed patients, this phenomenon may only partially overlap the depressive syndrome in time. Negative DST results in patients with primary depression must be interpreted in this light.     

Plasma ACTH levels in depression before and after recovery: relationship to the dexamethasone suppression test

Sixteen patients with major depressive disorder who were nonsuppressors on the dexamethasone suppression test (DST) on hospital admission were studied for plasma levels of adrenocorticotropic hormone (ACTH). Eight patients reverted to normal suppression with clinical recovery, while eight remained nonsuppressors. There was a significant reduction of ACTH levels in those who normalized on their DST, while ACTH levels remained high in the group that continued to be nonsuppressors. The results favored the hypothesis that dexamethasone nonsuppression in depression is mediated by high ACTH levels.     

TRH test, DST, and response to desipramine in primary degenerative dementia

The relationship of primary degenerative dementia (PDD) to major depressive disorder (MDD) is important clinically and theoretically. Neuroendocrine challenge strategies in PDD have focused primarily on the hypothalamic-pituitary-adrenal axis, have had varied results, and have not been coupled with assessment of response to antidepressant therapy. We studied the Thyrotropin-Releasing Hormone (TRH) test, the Dexamethasone Suppression Test (DST), and response to desipramine in 12 patients with PDD and 10 patients with MDD. The PDD patients had a high percentage of abnormal TRH tests and DSTs. This was not associated with improvement on desipramine.     

Affective disturbance in eating disorders

Thirty-three bulimic and 14 restrictive anorexics were compared on DSM-III diagnoses of affective and anxiety disorders, observer-rated and self-rated measures of depression and anxiety, and family history. A subgroup of 18 eating disorder subjects was administered the dexamethasone suppression test. The same 18 subjects were compared to 13 subjects with affective disorder on the Schedule for Affective Disorders and Schizophrenia. It was found that a large group with bulimia and restrictive anorexia nervosa was subject to a depressive disorder. Thirty-eight percent of the sample fulfilled criteria for a major depressive episode. The dysphoric experience seemed as intense in the bulimic and restricter group. There was a high incidence of dexamethasone nonsuppression (55%), which was found to be related to various measures of depression. Bulimics and restricters differed in their family history of affective disorder. While 61% of bulimics had a positive history of depression, this was found in only 23% of restricters (p less than .03).