Depression vulnerability and 5-hydroxytryptophan prophylaxis.

Previous studies have indicated that (1) The group of vital (endogenous) depressions encompasses a subgroup with a central serotonin (5-hydroxytryptamine; 5-HT) deficiency. (2) Abolition of this deficiency--with the aid of 5-hydroxytryptophan (5-HTP), a 5-HT precursor, or clomipramine, a 5-HT reuptake inhibitor--leads to abatement of depressive symptoms. It therefore seems plausible that the suspected 5-HT deficiency contributes to the development of depressive symptoms instead of resulting from them. (3) In a majority of patients, the suspected 5-HT deficiency persists even when the depressive symptoms have disappeared and the medication has been discontinued. This suggested that the disturbed central 5-HT metabolism is not a direct causal, but a predisposing factor. If so, abolition of the suspected 5-HT deficiency, e.g., with the aid of 5-HTP, would be expected to have a prophylactic effect. As predicted, 5-HTP was found in the present study to reduce the relapse rate in recurrent vital depressions with both a unipolar and bipolar course. The prophylactic effect was most pronounced in patients with persistent disorders of central 5-HT metabolism; this observation, however, requires corroboration. 5-HTP prophylaxis is the first aimed (i.e., pathological substrate-oriented) type of chemoprophylaxis known in psychiatry.