a b s t r a c tCONTEXT: Most double-blind studies of efficacy and tolerability of sertraline as compared to tricyclics in the treatment of late-life major depression have used amitriptyline as a standard, leading to the inevitable conclusion that the former drug is better tolerated than the latter, with both being equally efficacious. OBJECTIVE:To compare the antidepressant efficacy and tolerability of sertraline (50 mg/day) and imipramine (150 mg/day) in the first 6 weeks of the treatment of major depression in the elderly. DESIGN:A randomized double-blind parallel study with 6 weeks of follow-up. SETTING:The psychogeriatric clinic at the Institute of Psychiatry, Hospital das Clínicas, Faculty of Medicine of the University of São Paulo.PARTICIPANTS: 55 severe and moderately depressed non-demented outpatients aged 60 years or more. INTERVENTION:Patients were assigned to sertraline 50 mg/day or imipramine 150 mg/day. MAIN MEASUREMENTS:CAMDEX interview. Psychiatric diagnosis followed the guidelines for "Major Depressive Episode" according to DSM-IV criteria. Severity of symptoms was evaluated using the "CGI" and "MADRS" scales. Cognitive state was assessed using the Mini-Mental State Examination. Side effects were assessed using the "Safetee-Up" schedule. RESULTS:Both groups had a significant decrease in depressive symptoms according to the MADRS scores after 6 weeks of treatment (P = 0.01). No significant differences between groups were detected regarding treatment outcome (t = 0.4; P = 0.7). Although the dropout rate was greater in the imipramine group, the overall tolerability among patients who completed the 6-week trial was similar in both test groups. CONCLUSIONS:Both sertraline and imipramine exhibited good efficacy and an acceptable side-effect profile for elderly depressed patients after 6 weeks of antidepressant treatment.KEY WORDS: Depression. Elderly. Antidepressant drugs. Tricyclics. Sertraline. SSRI's.• and are among the most widely prescribed of such medications. 9-11A recent meta-analysis study of efficacy, safety and tolerability of four antidepressant classes concluded there were no differences between outcomes in the management of late-life major depression, 12 suggesting that there is little advantage for each antidepressant class over the others, namely SSRI's, tricyclics, reversible inhibitors of monoamine oxidase-A and atypical antidepressants. Nevertheless, such finding can only be generalized for samples of selected patients. In the presence of concurrent medical illnesses, or physical and cognitive conditions, accurate clinical judgement must be relied upon for the correct choice of antidepressant, as the use of certain drugs is limited by the risk of toxicity, pharmacokinetic interactions or intolerable side-effects.Although more risky and laborious to prescribe, the clinician must be aware of the putative benefits of tricyclic antidepressants in the treatment of depressive disorders in the elderly. Besides being effective, tricyclics are cheaper and more widely available than the new c...