We studied 75 patients on prophylactic antidepressants (imipramine or amitriptyline) to examine the effect of antidepressant dose on long-term prophylaxis of depression and to see whether lowering the dose during the prophylactic period affected subsequent relapse. There was no statistically significant difference in maintenance and prophylactic doses between the group that completed the 2 years free of a depressive episode, the group that had a depressive relapse and the group that dropped out of treatment before the end of the prophylactic period. However, the group that completed the 2 years free of a depressive episode had significantly less of a difference between the maintenance and prophylactic doses than the other 2 groups. Overall, 11/31 who remained on the same dose during the prophylactic period vs the maintenance period relapsed vs 17/25 who had their dose lowered during the prophylactic period vs the maintenance period. The difference was statistically significant.