Efficacy of lithium-tranylcypromine treatment in refractory depression

Twelve inpatients with major depression refractory to at least two controlled antidepressant trials had tranylcypromine added to ongoing lithium treatment. Eleven patients showed reliable improvement in nurses' depression ratings compared with a prior trial of lithium added to an antidepressant that was not a monoamine oxidase inhibitor (MAOI). Eight patients were blindly judged much or very much improved, and all 12 patients improved sufficiently to be discharged. Preclinical studies of conjointly administered lithium and MAOIs suggest that central serotonergic pathways may mediate this robust clinical effect.