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

J Affect Disord. 2001 Aug;65(3):243-52. doi: 10.1016/s0165-0327(00)00225-1.


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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amitriptyline / adverse effects
  • Amitriptyline / therapeutic use*
  • Double-Blind Method
  • Drug Monitoring
  • Female
  • Fluoxetine / adverse effects
  • Fluoxetine / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Patient Compliance / psychology*
  • Patient Dropouts / psychology
  • Risk


  • Fluoxetine
  • Amitriptyline