Mohammed T. Abou-Saleh

Principles and Practice of Geriatric Psychiatry.Editors: Professor John R. M. Copeland, Dr Mohammed T. Abou-Saleh and Professor Dan G. BlazerCopyright & 2002 John Wiley & Sons LtdPrint ISBN 0-471-98197-4 Online ISBN 0-470-84641-081Laboratory Diagnosis:Dexamethasone Suppression TestMohammed T. Abou-SalehSt George’s Hospital Medical School, London, UKThere is little doubt that the application of the dexamethasonesuppression test (DST) for the management of depressive illnesshas provided one of the most dramatic developments in biologicalpsychiatry. Extensive investigations of this test began in the late1960s and culminated in its introduction as a highly specificdiagnostic test for endogenous depression 1 . There have beenhundreds of studies on its use in diagnosis, in management and asa paradigm for investigating the pathophysiology of depressiveillness.Carroll 2 proposed that the DST was a highly specific diagnostictest for endogenous depression, with a specificity of 96% and asensitivity of 50%. This claim has not been substantiated by otherinvestigators, who reported high rates of non-suppression in avariety of psychiatric conditions, including non-endogenousdepression 3 , dementia 4 , schizophrenia and alcoholism 5 . AbnormalDST results have also been obtained in mania 6 and eatingdisorders 7 . These findings have been repeatedly confirmed byother investigators and the clinical utility of the DST in thediagnosis and management of depression has been criticallyreviewed 1 .METHODOLOGICAL CONSIDERATIONSMost studies have used the overnight DST, with 1 mg dexamethasoneadministered before midnight for cortisol estimation at4 p.m. the following day. A cortisol of 50 ng/ml and above is takenas the criterion for non-suppression. A number of methodologicalaspects have been investigated, including sampling time, dexamethasonedose, the cortisol criterion for non-suppression, theassay technique and the bio-availability of dexamethasone. Thecriterion for non-suppression has been empirically determined bytrading off the test’s sensitivity and specificity, aiming for aspecificity of over 90% and a sensitivity of 50%. Carroll’scriterion of 50 ng/ml for non-suppression has been universallyadopted, in spite of the great variation in sensitivity and specificityachieved in various centres.Perhaps the most important contributing variable to the DSTresults is the dose of dexamethasone administered: the 1 mg DSThas higher sensitivity and lower specificity than 2 mg DST. Acorollary of the dose of dexamethasone is the correspondingplasma concentration achieved and its relationship to the resultsof the dexamethasone test: levels of dexamethasone in nonsuppressorsare lower than in suppressors 8 . The extent to whichdifferences in bio-availability of oral dexamethasone account fordifferences in sensitivity and specificity of the DST for depressionis variable. The application of dexamethasone ‘‘windows’’ couldreduce this source of test variance 8 . Dexamethasone metabolism isinfluenced by liver function in males and by body mass infemales 9 . The combination of DST with corticotropin releasingfactor has been shown to be more closely associated withhypothalamic–pituitary–adrenal (HPA) activity than DST indepressed and normal subjects 10 .The influence of non-specific factors on the results of the DSThas been reviewed 1 ; factors studied included the degree of stress,ageing, the presence of physical illness, marked weight loss, andthe effects of administration and withdrawal of psychotropicdrugs.An association between increasing age and non-suppression hasbeen shown in depressive and demented patients and in normalcontrols 11 . However, a longitudinal study in elderly normalsubjects followed up for a period of 2.5 years showed no effectof age and suggested that genetic factors may influence the setpoint of the HPA axis 9 . Physical illness is associated with nonsuppression,particularly diabetes mellitus and hypothalamicdisorders.The list of drugs that interfere with the DST has beenincreasing, and includes hormonal preparations, liver enzymeinducingdrugs such as barbiturates, anticonvulsants and alcohol.Test results are not affected by normal doses of benzodiazepines,antidepressants and neuroleptics. High doses of benzodiazepineshave been associated with normal suppression. The effects ofwithdrawing psychotropic medication have also been studied,with higher rates of non-suppression being observed in patientswho discontinued antidepressants, neuroleptics and benzodiazepines.These non-specific factors have important effects on testresults and must be ascertained when the DST is carried out in theclinical situation. They have undoubtedly contributed to theconsiderable variation in the rate of non-suppression in normalcontrols and psychiatric patients.DIAGNOSTIC VALUEThe claim that the DST is a highly specific diagnostic test forendogenous depression (melancholia) has not been substantiated.Rates of non-suppression in endogenous depressionvaried (18–81%), a variation that may be partly related to thecriteria used to define endogenous depression. An early reviewfound that in 12 out of 20 studies, significant increases in nonsuppressionrates were found in endogenous compared with nonendogenousdepressives, with the Newcastle Scale providingPrinciples and Practice of Geriatric Psychiatry, 2nd edn. Edited by J. R. M. Copeland, M. T. Abou-Saleh and D. G. Blazer&2002 John Wiley & Sons, Ltd