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


METHODS
Nine-week double blind, randomized controlled trial.


METHODS
Ambulatory psychiatric care.


METHODS
Random sample of 66 depressed (DSM-III-R criteria) patients.


METHODS
Fluoxetine 20 mg or amitriptyline 150 mg.


METHODS
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.
Demyttenaere
K
K
Department of Psychiatry, University Hospital Gasthuisberg, Herestraat 49, B3000 Leuven, Belgium. keon.demyttenaere@med.kuleuven.ac.be
Mesters
P
P
Boulanger
B
B
Dewe
W
W
Delsemme
M H
MH
Gregoire
J
J
Van Ganse
E
E
D000328:Adult; D000639:Amitriptyline / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D016903:Drug Monitoring; D005260:Female; D005473:Fluoxetine / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance / Q000523:psychology*; D010352:Patient Dropouts / Q000523:psychology; D012306:Risk
D005473:Fluoxetine; D000639:Amitriptyline