Assessing rates and predictors of tachyphylaxis during the prevention of recurrent episodes of depression with venlafaxine ER for two years (PREVENT) study.
BACKGROUND
Antidepressant tachyphylaxis describes the return of apathetic depressive symptoms, such as fatigue and decreased motivation, despite continued use of a previously effective treatment.


METHODS
Data were collected from a multiphase, doubleblind, placebo-controlled study that assessed the efficacy of venlafaxine extended release (ER) during 2 sequential 1-year maintenance phases (A and B) in patients with recurrent major depressive disorder (MDD). The primary outcome was the cumulative probability of tachyphylaxis in patients receiving venlafaxine ER, fluoxetine, or placebo. Tachyphylaxis was defined as Rothschild Scale for Antidepressant Tachyphylaxis (RSAT) score </= 7 in patients with prior satisfactory therapeutic response. A Kaplan-Meier estimate of the cumulative probability of not experiencing tachyphylaxis, and a 2-sided Fisher exact test was used to assess the relationship between tachyphylaxis and recurrence.


RESULTS
The maintenance phase A population was comprised of 337 patients (venlafaxine ER [n = 129], fluoxetine [n = 79], placebo [n = 129]), whereas 128 patients (venlafaxine ER [n = 43], fluoxetine [n = 45], placebo [n = 40]) were treated during maintenance phase B. No difference in the probability of experiencing tachyphylaxis were observed between the active treatment groups during either maintenance phase; however, a significant difference between venlafaxine ER and placebo was observed at the completion of maintenance phase A. A significant relationship between tachyphylaxis and recurrence was observed.


CONCLUSIONS
Despite demonstrating psychometric validity and reliability, the current definition of tachyphylaxis has not been widely studied.


CONCLUSIONS
Although no significant differences were observed in the probability of tachyphylaxis among patients receiving active treatment, the relationship between tachyphylaxis and recurrence suggests that tachyphylaxis may be a prodrome of recurrence.
Rothschild
Anthony J
AJ
University of Massachusetts Medical School, Worcester, MA, USA. anthony.rothschild@umassmemorial.org
Dunlop
Boadie W
BW
Dunner
David L
DL
Friedman
Edward S
ES
Gelenberg
Alan
A
Holland
Peter
P
Kocsis
James H
JH
Kornstein
Susan G
SG
Shelton
Richard
R
Trivedi
Madhukar H
MH
Zajecka
John M
JM
Goldstein
Corey
C
Thase
Michael E
ME
Pedersen
Ron
R
Keller
Martin B
MB
D000328:Adult; D003511:Cyclohexanols / Q000494:pharmacology* / Q000627:therapeutic use; D003692:Delayed-Action Preparations; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D055502:Secondary Prevention; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D013618:Tachyphylaxis; D016896:Treatment Outcome; D000069470:Venlafaxine Hydrochloride
D003511:Cyclohexanols; D003692:Delayed-Action Preparations; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride