The contribution of drug research to investigating the nature of endogenous depression.

A relationship between brain monamines and endogenous depression is suggested by observations on the mode of action of drugs producing or alleviating depressive symptoms. For example, reserpine is capable of faithfully mimicking the clinical picture of endogenous depression, which may be related to monoamine depletion. On the other hand, antidepressant drugs, e.g. the monoamine oxidase inhibitors, the tricyclic antidepressants and the monoamine precursors appear to increase the availability of monoamines at postsynaptic receptor sites. The different classes of antidepressant agents in general appear to potentiate each other's actions, according to animal data and clinical observations. Studies on the mode of action of tricyclic antidepressants with different profiles and on monoamine precursors suggest that 5-hydroxytryptamine is primarily involved in the control of mood, and noradrenaline in psychomotor activity. Clincial investigations initiated by the drug studies have demonstrated changes in monoamine metabolism in endogenous depression. The available evidence thus suggests a causal relationship between disturbances in monoamine metabolism and depression.