Efficacy of desipramine in endogenomorphically depressed patients

This study was designed to test the hypothesis that there are 2 biochemical subgroups of 'endogenously' depressed patients--serotonin-deficient and noradrenalin-deficient groups--which respond differently to antidepressants depending on relative blockade of serotonin vs. norepinephrine (NE) reuptake. Patients with pervasive anhedonia and autonomy of depressed mood (endogenomorphic depressives) were treated first with the noradrenergic agent desipramine (DMI), then, if still depressed, such patients were randomized double-blind to continued DMI or clomipramine (CMI), a primarily serotonergic agent. Of 34 such endogenomorphically depressed patients 2 responded during a placebo period and 5 dropped out. Of 27 patients completing at least 4 weeks of DMI (mean maximum daily dose 283 mg, range 100-400 mg/d), 23 (85.2%) responded. With only 4 nonresponders, the second, or CMI, part of the study had to be abandoned. Since DMI strongly blocks neuronal reuptake of catecholamines with little effect on serotonin reuptake, these results suggest that endogenomorphic depressives may have a relatively homogeneous catecholamine deficiency. Alternatively, DMI may exert its effect by a mechanism other than blockade of EN reuptake. Eleven of the endogenomorphically depressed patients also met Research Diagnostic Criteria for situational depression (reactive). Ten of these 11 responded to DMI suggesting that presence or absence of a precipitant may be irrelevant in predicting response to tricyclic antidepressants in endogenomorphic depressions. Mean blood levels drawn at equivalent DMI dose were 238 ng/ml (range, 48-712) for responders, and 352 ng/ml (range, 160-877) for non-responders, indicating that patients appear to respond to DMI across a wide range of blood levels and suggesting the absence of a narrow therapeutic window.