This study will attempt to address several critical areas in treatment of geriatric depression, namely: (a) Is chronic antidepressant prophylaxis (beyond 20 weeks) necessary in geriatric patients who have recovered from an acute depressive episode? (b) Does chronic tricyclic maintenance therapy decrease recurrence rates in geriatric depression? (c) Does Li+ maintenance therapy decrease recurrence rates of depression in the elderly? (d) What are the medical and neuropsychological sequelae of chronic Li+ prophylaxis in the elderly? (e) What concurrent medical conditions and medications interfere with the effectiveness of the antidepressant strategies under study? All patients over the age of 60 will be given extensive medical, neurological, laboratory, neuropsychological and psychodiagnostic evaluations. Patients meeting diagnostic criteria for major depression will be treated in a standard fashion with the tricyclic nortriptyline (NT). After a stabilization period of 20 weeks on NT alone has been achieved, patients who have responded to treatment and are considered in remission will then be randomized to receive 1) placebo with gradual discontinuation of NT, 2) maintenance NT alone or 3) maintenance Li+. Patients in each group will then be followed for a period of two years and monitored for recurrence of their depressive disorder. In addition, possible side-effects associated with long-term use of lithium on nortriptyline will be closely monitored through periodic assessments of serum levels, clinical status, self-reported complaints (as measured by a side-effects checklist), and neuropsychological functioning. An attempt will be made to determine which side effects are most prevalent, most bothersome, and most likely to lead to non-compliance. A second component of the study will evaluate the prophylactic effects of NT or Li+ on recurrent depression in patients who have received ECT for medication resistant depression. Patients will be offered ECT if they have not responded to NT after 4 weeks with a therapeutic serum level. Twenty weeks after ECT has been completed and patients are stable, patients will then be randomly assigned to maintenance therapy groups as outlined above. Patients will then be followed similarly to the patients in the final component of the study. To summarize, the overall long-term objectives of this study are to examine the efficacy of particular antidepressant strategies in minimizing recurrence rates of depression and to explore possible associated side-effects of these treatments in a geriatric population.
