Spironolactone prophylaxis in manic-depressive disease.

Lithium is now recognized as the drug of choice for the prophylactic control of manic-depressive disease, but its mechanism of action is the nonspecific inhibition of adenyl cyclase and subsequent cAMP formation which produces many undesirable side effects. However, the effect that lithium has on the central nervous system is compatible with all three theories regarding the basis of affective disorders, i.e., the biogenic amine theory, the electrolyte theory, and the membrane theory. Fluctuations of the hormone aldosterone during the various stages of manic-depressive disease could account for an etiological mechanism, that also is compatible with all three theories. Both spironolactone and lithium can inhibit the action of aldosterone. Therefore, when six manic-depressive patients, who had been well maintained on lithium, requested discontinuance of this drug because of side effects, spironolactone was substituted. On a minimum 1-year follow-up study, five of the six patients were well maintained on this new drug regimen.