Clinical investigations into antidepressive mechanisms

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Abstract
– This prospective study investigates the possibility of a central noradrenergic-cholinergic imbalance in subgroups of depressed inpatients using the dexamethasone suppression test (DST) as one peripheral indicator. The DST was performed in 43 depressed inpatients. Subsequently, a group (n= 20) of DST suppressors (DST-) and a group (n= 23) of DST nonsuppressors (DST+) were treated under double blind conditions with either nomifensine (NOM) a nor-adrenaline potentiating drug, or amitriptyline (AMI) a noradrenaline potentiating and strong anticholinergic compound. DST+ depressives responded favorably to AMI, but not to NOM. Conversely, DST- depressives responded favorably to NOM but less well to AMI. Together with other biochemical findings this data suggests: 1) a hypo-function of the noradrenergic system in DST- patients who may, from a clinical point of view, usually show minor or ‘neurotic’ depressions; 2) a hypofunction of the noradrenergic and a hyperfunction of the cholinergic system in DST+ patients who may present a more severe or ‘endogenous’ depression. These data suggest a biochemical heterogeneity of depression and offer an aid for a more specific antidepressive drug therapy.