• The efficacy of lithium carbonate plus imipramine hydrochloride vs lithium carbonate plus placebo in preventing relapse was assessed in a prospective, hydro- doubleblind study of 75 bipolar 1 patients. Outcome measures included type of relapse, time until relapse, and subsequent illness course. Infrequent depressive relapse in either treatment group precluded any demonstration of an advantage of adding imipramine to a lithium carbonate regimen. There was little evidence that the combination of lithium carbonate and imipramine caused adverse reactions. However, interactions between type of most recent episode, treatment condition, sex, and type of relapse showed that women and mania-prone patients treated with imipramine had an increased risk of mania. Life table analysis showed that the overall probability of remaining well was the same for both treatment groups and that two thirds of all relapses occurred in the first six months.
Quitkin FM, Kane J, Rifkin A, Ramos-Lorenzi JR, Nayak DV. Prophylactic Lithium Carbonate With and Without Imipramine for Bipolar 1 PatientsA Double-blind Study. Arch Gen Psychiatry. 1981;38(8):902-907. doi:10.1001/archpsyc.1981.01780330060006