Tachyphylaxis/tolerance to antidepressants

Tachyphylaxis/tolerance to antidepressants in treatment of dysthymia: Results of a retrospective naturalistic chart review studypcn_2231 499..504
Gregory Katz, MD*
The Jerusalem Mental Health Centre–Kfar Shaul Psychiatric Hospital, Hadassa Medical School, Hebrew University, Jerusalem, Israel
Aim: The main goals of this chart-review study were to examine the rate of tachyphylaxis during treat- ment of dysthymia with antidepressants, to compare the incidence of tolerance during trials of selective serotonin reuptake inhibitors (SSRI) and non-SSRI and to give descriptive analysis of the cases of tachyphylaxis.
Methods: The retrospective naturalistic chart review study included 52 cases of successfully treated (with different antidepressants) patients suffering from dysthymia. The overall number of the cases of toler- ance to antidepressants were registered as well as the rate of these phenomena in the groups treated with SSRI and non-SSRI.
DISCUSSION
The results of the survey indicated the high possi- bility of developing tolerance to SSRI antidepres- sants during treatment of dysthymia. Although the elevated rate of tachyphylactic cases in SSRI-treated patients was hypothesized, the real frequency of the phenomena appeared to be surprisingly high with no such symptoms in the non-SSRI group. Prominent differences between SSRI and other anti- depressants concerning the issue of tolerance to medications in major depression were reported in some studies. In a retrospective study, Posternak and Zimmerman7 compared rates of tachyphylaxis of TCA and venlafaxine, which act as dual reuptake inhibitors (though usually in high dosages) versus SSRI. The cohort reported having undergone 326 prior SSRI trials, 47 prior venlafaxine trials, and 35 prior trials with a TCA. Rates of tachyphylaxis were significantly lower with the dual reuptake inhibitors venlafaxine and TCA (3.7%) compared to rates of tachyphylaxis with SSRI (14.1%). Serotonin receptor desensitization has been hypothesized to be the primary actor responsible for the observation of an increased risk for the return of depressive symptoms during long-term treatment with selective serotonin reuptake inhibitors.14 The data of higher frequency of ‘poop out’ effect in SSRI medications compared to the dual reuptake inhibitors in the present study as well as in some others could be seen as an indi- rect support to this hypothesis. A multiphase, double-blind, placebo-controlled study assessed the efficacy of venlafaxine extended release (ER) during two sequential 1-year maintenance phases (A and B) in patients with recurrent major depressive disorder.15 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], flu- oxetine [n = 45], placebo [n = 40]) were treated during maintenance phase B. No differences in the probability of experiencing tachyphylaxis were observed between the active treatment groups during either maintenance phase; however, only two medications from the SSRI and SNRI groups

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