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

Author(s): Demyttenaere K, Mesters P, Boulanger B, Dewe W, Delsemme MH, Gregoire J, Van Ganse E

Affiliation(s): Department of Psychiatry, University Hospital Gasthuisberg, Herestraat 49, B3000 Leuven, Belgium. keon.demyttenaere@med.kuleuven.ac.be

Publication date & source: 2001-08, J Affect Disord., 65(3):243-52.

Publication type: Clinical Trial; Multicenter Study; Randomized Controlled Trial

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.