Mohammed T. Abou-Saleh

462 PRINCIPLES AND PRACTICE OF GERIATRIC PSYCHIATRYbetter discrimination than studies using the Research DiagnosticCriteria and DSM-III criteria 12 .The Research Diagnostic Criteria for distinction betweenendogenous and non-endogenous depression have been validatedby the DST 13 . Mitchell 14 studied the DST in relation to the Coresystem (objective signs of psychomotor disturbance), Newcastlescale and DSM-III-R melancholia: all three definitions wereassociated with DST results. The Core index, but not theNewcastle scale, was associated with cortisol levels and dexamethasonelevels after partialling out the effects of age andbaseline cortisol levels. A meta-analysis of studies of the DST inrelation to psychotic/non-psychotic depression (14 studies) andmelancholic/non-melancholic depression (19 studies) reported astrong association of DST non-suppression and psychoticdepression (64.1%) vs. non-psychotic depression (41%) 15 . TheDST has good discriminating power between patients with severepsychiatric disorders, including major affective disorders, acutepsychoses and dementia and patients with chronic conditions,such as dysthymic disorders (neurotic depression), chronicschizophrenia, anxiety, panic disorders and acute grief. Thespecificity of the test is higher in normal controls (93%) andlowest in manic patients (51%). It has satisfactory sensitivity andspecificity for diagnosing secondary depression in patients withstroke. DST non-suppression after 3 months from acute strokepredicts the occurrence of depression 3 years later 16 . A review ofnine studies reported a median sensitivity of 47% and specificityof 87%, suggesting the DST’s utility for the evaluation of poststrokedepression 17 . However, an interesting feature is the higherrate of non-suppression in demented patients with depressivesymptoms than in those without.PROGNOSTIC VALUEThe prognostic value of the DST has been evaluated by examiningthe clinical outcome following antidepressive treatments insuppressors and non-suppressors, by examining changes insuppression status in relation to clinical change, and by evaluatingdifferences in long-term outcome between non-suppressors wholater converted to normal suppression and those who remainednon-suppressors. Initial studies of the predictive value of the testindicated a more favourable response to antidepressant treatmentin non-suppressors than in suppressors. Coppen et al. 18 , however,failed to find a difference in therapeutic outcome betweensuppressors and non-suppressors, classified on the basis of thetraditional cut-off point (50 ng/ml) for cortisol level, but foundthat non-suppressors had more favourable responses to bothantidepressants and electroconvulsive therapy (ECT) when thecriterion for non-suppression was taken as a plasma controlconcentration of 100 ng/ml and above. Non-suppression confers asmall advantage (1%) over suppression in predicting a morefavourable response to antidepressant therapy. DST statuspredicted improvement on nortriptyline, but not moclobemideor placebo 19 .Changes in DST status have also been examined in relation tolong-term outcome: persistent non-suppression has been associatedwith a greater risk of relapse within several months oftreatment. Depressive patients who continued to be nonsuppressorshad a relapse or a fatal outcome in 77% of cases,while only 19% of those who had a conversion to normalsuppression had such outcome 20 . In depressive disorders, Coryelland Schlesser 21 recently reported DST non-suppression to bemore powerful than clinical factors in predicting completedsuicides: survival analyses over 15 years showed that the estimatedrisk for eventual suicide was 27% in those with DST nonsuppressioncompared to 3% in those with normal DST. Inelderly depressive patients, post-dexamethasone cortisol levelswere associated with clinical improvement and high cortisolism(150 mg/ml), and predicted improvement in delusional depression22 . In six out of nine studies, patients with DST nonsuppressionfollowing ECT had a higher rate of relapse thansuppressors 23 . The value of the DST in predicting outcomefollowing discharge has also been investigated in patients withschizophrenia and mania: non-suppressors had a more favourableclinical outcome after 6 months, and those manic patients whobecame suppressors before discharge had better outcomes afterdischarge than those who continued to be non-suppressors. Inpatients with senile dementia of the Alzheimer type who haddepressive symptoms and who were non-suppressors, a trial ofcitalopram, a highly specific 5-hydroxytryptamine (5-HT)-uptakeinhibitor was associated with improvement in these depressivesymptoms and normalization of the DST 24 .COMMENT AND CONCLUSIONSThe introduction of the DST for the investigation of thepsychobiology of depression has been a landmark developmentin biological psychiatry: it has had unprecedented evaluation andhas been shown to be one of the most reproducible findings in thesearch for biological markers for depression. The balance ofevidence indicates that the overnight 1 mg DST, with one plasmacortisol estimation in the afternoon of the next day and a cut-offpoint of 50 ng/ml has satisfactory sensitivity for depressive illnessand high specificity when its results are compared with thoseobtained in normal controls and patients with minor psychiatricconditions and chronic schizophrenia. The specificity of the testfor depression is unsatisfactory in comparison with otherpsychoses, including mania, schizophrenia and dementia. Thesensitivity of the test is highest for severe depression withendogenous/psychotic features, mixed affective states and depressionin old age. The test has little value in predicting response toantidepressants and ECT but provides a useful monitor of clinicalprogress and is a good predictor of long-term outcome: continuednon-suppression or reversion from suppression to non-suppressionduring treatment or follow-up is an ominous sign thatindicates a greater risk of relapse in the months followingtreatment. The influence of non-specific factors on the DST isconsiderable. Factors such as age, stress, weight loss, alcoholmisuse, administration of anticonvulsants, withdrawal of psychotropicmedication, presence of diabetes mellitus and the bioavailabilityof dexamethasone are important contributing factorsto the test results. These factors, however, do not account for thevariation in test results that appear to be essentially related to thebiological process underlying depression. The 2 mg test hasgreater specificity, but lower sensitivity, than the 1 mg test andits diagnostic and prognostic value requires further investigation.The DST is only an aid to diagnosis and prognosis, aspects thatshould be essentially based on careful clinical assessment. Theabnormal result provides a ‘‘physical sign’’ indicating biologicaldepression. The DST test, like any other laboratory investigation,may increase the diagnostic confidence of the clinical diagnosis,but could never replace careful clinical assessment. The test isparticularly useful in the assessment of biological depressionassociated with neurotic disorders, personality disorders, griefreaction and physical illness. Moreover, the presence of this‘‘physical sign’’ indicates the necessity for vigorous physicaltreatment, or at least the use of a combined physical–psychologicalapproach to such conditions as agoraphobia, obsessionalillness and grief reaction, and the test may be particularly useful inmonitoring the course of the illness and predicting its long-termoutcome. Patients who continue to be non-suppressors are likelyto relapse following recovery, and to require more intensivefollow-up and continuation or maintenance of prophylactic