Current perspectives in the pharmacopsychiatry of depression and mania

The observation that opiates and endorphins exert euphorogenic effects in normal probands points to a possible involvement of endorphins in different types of affective disorders. There are several powerful arguments that the activation of particular central opiate receptors (e.g. by "opium cure", beta-endorphin, partial agonists, release of endorphins via electroconvulsion) exerts curative effects in endogenous depression. Results from a double-blind investigation of the possible antidepressant action of the opiate partial agonist buprenorphine in patients with endogenous depression revealed a strong antidepressant effect of this substance. A series of anticonvulsants, possibly acting via a GABA-ergic-like mechanism (valproate, dipropylacetamide, carbamazepine and oxcarbazepine), have recently been shown by different groups to possess antimanic and also, partially, antidepressant properties. Furthermore, a synergistic mode of action in the prophylaxis of manic episodes has been observed as concerns valproate and lithium. On the other hand, there is some evidence from both in vitro and in vivo animal experiments that chronic application of lithium results in a modification of the GABA-turnover. The present paper reviews the present state of knowledge concerning the concept of a GABA-dependent regulation of affective states.