Clinical and Metabolic Studies with Imipramine in Man

Six out of seven severely depressed patients improved rapidly on very high doses of imipramine. Clinical improvement correlated well with drug blood levels, which varied greatly from patient to patient and were characteristic of individual patients rather than of dose. Three out of five of the same patients receiving a combination of presumptive inhibitors of drug-metabolizing enzymes and imipramine had drug blood levels comparable to those of two patients receiving high doses of imipramine alone. Further study is underway to clarify the human pharmacology of these two therapies.