Adherence to treatment regimen in depressed patients treated with amitriptyline or fluoxetine

Abstract

Objective: Non-compliance presents a constant challenge to effective therapy. Many studies only investigate early treatment discontinuation and not other measures like adherence to treatment regimen. We compared adherence in depressed patients using either a selective serotonin reuptake inhibitor (fluoxetine) or a tricyclic antidepressant (amitriptyline), and examined its clinical relevance through adverse events, drop-out rates, and outcome. Adherence was measured electronically with the MEMS (Medication Event Monitoring System). Design: Nine-week double blind, randomized controlled trial. Setting: Ambulatory psychiatric care. Patients: Random sample of 66 depressed (DSM-III-R criteria) patients. Intervention: Fluoxetine 20 mg or amitriptyline 150 mg. Main outcome measures: Time course of adherence and its relation to severe adverse events, drop-outs and outcome. Results: Non-adherence to the treatment regimen occurred frequently in both treatment groups: 31% of patients had at least one 3-day drug holiday, and 34% of patients had at least one episode of three pills in a 24-h period. Over-consumption occurred more frequently during the early phases of treatment while under-consumption occurred more frequently during the later phases. Patients on amitriptyline ( P=0.03) and patients with a higher pill intake ( P=0.01) experienced more severe adverse events. Patients on amitriptyline ( P=0.009) and patients with a lower adherence to the treatment regimen ( P=0.004) discontinued from treatment more frequently. The final Hamilton score was significantly predicted by a longer duration of treatment and by a better adherence, but only in amitriptyline users. Conclusions: Non-adherence to the treatment regimen has important clinical consequences. Pharmacodynamics and human behavior predict risk for severe adverse events and drop-outs. Moreover, in amitriptyline users but not in fluoxetine users, better adherence predicts a better outcome.