Recurrence of depression after discontinuation of long-term amitriptyline treatment

In this study 10 of 17 patients receiving long-term amitriptyline treatment (average duration: 3.7 years, average dose: 138 mg) had their medication tapered and discontinued under double-blind conditions. Eight became depressed within 3 to 15 weeks. None of the 7 control subjects became depressed during the 6 months of the study. Those who became depressed also showed psychomotor retardation and sleep disturbance. Relief of longstanding anticholinergic side effects followed medication discontinuation. Some patients whose amitryptyline was discontinued experienced a mild withdrawal syndrome within the first 2 weeks, consisting of irritability, dream and sleep disturbance, and restlessness during the first few weeks.