Tachyphylaxis after repeated antidepressant drug exposure in patients with recurrent major depressive disorder.
OBJECTIVE
The aim of this post hoc analysis was to examine whether tachyphylaxis occurs after repeated courses of antidepressant drug therapy.


METHODS
276 patients with major depressive disorder (MDD) were treated with sertraline (150-200 mg daily) for 8 weeks. Patients with persistent MDD after sertraline therapy were randomized to continuation therapy with either sertraline plus atomoxetine (n = 72) or sertraline plus placebo (n = 74) for 8 additional weeks. Logistic regression was used to test the hypothesis that an increase in prior antidepressant drug exposure is associated with a reduced responsiveness to sertraline therapy.


RESULTS
The number of prior antidepressant drug exposures was negatively associated with response to initial sertraline therapy (odds ratio = 0.81, p = 0.0035). The odds ratio indicates a 19.9% reduced likelihood of response with each prior antidepressant treatment trial. In contrast, the number of prior antidepressant treatment trials was not associated with response to continuation sertraline plus atomoxetine or sertraline plus placebo therapy.


CONCLUSIONS
This observation supports the hypothesis that tachyphylaxis may develop after repeated antidepressant drug trials.
Amsterdam
Jay D
JD
Depression Research Unit, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-3309, USA. jamsterd@mail.med.upenn.edu
Williams
David
D
Michelson
David
D
Adler
Lenard A
LA
Dunner
David L
DL
Nierenberg
Andrew A
AA
Reimherr
Frederick W
FW
Schatzberg
Alan F
AF
D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000069445:Atomoxetine Hydrochloride; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio; D011437:Propylamines / Q000008:administration & dosage / Q000627:therapeutic use; D012008:Recurrence; D020280:Sertraline / Q000008:administration & dosage / Q000627:therapeutic use*; D013618:Tachyphylaxis; D016896:Treatment Outcome
D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D011437:Propylamines; D000069445:Atomoxetine Hydrochloride; D020280:Sertraline