An attempt is made to relate drug and non-drug antidepressive interventions to brain processes. In the present context two concepts are proposed: vulnerability towards depressogenic factors and depression as a state of the brain. Accordingly, it is assumed that the current antidepressants make the brain less vulnerable by inhibiting monoaminergic neurons and by reducing the number or efficacy of their postsynaptic receptors. In contrast, electroconvulsive therapie and sleep-deprivation affect primarily the state of the brain and can produce spectacular (but often short lasting) improvements. It is proposed that the combination of the two aspects may lead to fast and lasting antidepressive effects.

In 1975 van den Burg and van den Hoofdakker hypothesized that depressed patients might be ‘overaroused.’ This suggestion is consistent not only with their seminal observations on the antidepressant effects of total sleep deprivation in depression, but with the short, fragmented, and shallow sleep of depressed patients, lowered arousal thresholds, hyperactivity of the hypothalamus-pituitary adrenal (HPA) axis, and elevated core body temperature commonly found in some patients during the sleep period.