The influences of CYP2D6 genotypes and drug interactions on the pharmacokinetics of venlafaxine: exploring predictive biomarkers for treatment outcomes
Fen JiangHae-Deun KimHan-Sung NaSeok‐Yong LeeDoo-Won SeoJong-Yeol ChoiJi-Hye HaHee-Jung ShinYoung-Hoon KimMyeon-Woo Chung
26
Citation
27
Reference
10
Related Paper
Citation Trend
Keywords:
Venlafaxine Hydrochloride
Paroxetine
Therapeutic Drug Monitoring
The authors report the CYP2D6 inhibitory effects of fluoxetine, paroxetine, sertraline, and venlafaxine in an open-label, multiple-dose, crossover design. Twelve CYP2D6 extensive metabolizers were phenotyped, using the dextromethorphan/dextrorphan (DM/DX) urinary ratio, before and after administration of fluoxetine 60 mg (loading dose strategy), paroxetine 20 mg, sertraline 100 mg, and venlafaxine 150 mg. Paroxetine, sertraline, and venlafaxine sequences were randomized with 2-week washouts between treatments; fluoxetine was the last antidepressant (AD) administered. Comparing within groups, baseline DM/DX ratios (0.017) were significantly lower than DM/DX ratios after treatment (DM/DXAD) with fluoxetine (0.313, p < 0.0001) and paroxetine (0.601, p < 0.0001) but not for sertraline (0.026, p = 0.066) or venlafaxine (0.023, p = 0.485). Between groups, DM/DXAD ratios were significantly higher for fluoxetine and paroxetine compared to sertraline and venlafaxine. No differences between DM/DXAD ratios were found for fluoxetine and paroxetine although more subjects phenocopied to PM status after receiving the latter (42% vs. 83%; chi 2 = 4.44, p = 0.049, df = 1). Similarly, no differences between DM/DXAD ratios were found for sertraline and venlafaxine. Of note, the DM/DXAD for 1 subject was much lower after treatment with paroxetine (0.058) compared to fluoxetine (0.490), while another subject exhibited a much lower ratio after treatment with fluoxetine (0.095) compared to paroxetine (0.397). Significant correlations between AD plasma concentration and DM/DXAD were found for paroxetine (r2 = 0.404, p = 0.026) and sertraline (r2 = 0.64, p = 0.002) but not fluoxetine or venlafaxine. In addition, DM/DXAD correlated with baseline isoenzyme activity for paroxetine, sertraline, and venlafaxine groups. These results demonstrate the potent, but variable, CYP2D6 inhibition of fluoxetine and paroxetine compared to sertraline and venlafaxine. CYP2D6 inhibition may be related, in part, to dose, plasma concentration, and baseline isoenzyme activity, and these correlations merit further investigation.
Paroxetine
Sertraline
Venlafaxine Hydrochloride
Crossover study
Cite
Citations (97)
Venlafaxine Hydrochloride
Paroxetine
Therapeutic Drug Monitoring
Cite
Citations (26)
Objective:To compare with efficacy and side effects between venlafaxine and paroxetine in the treatment of depression.Methods:52 inpatients and outpatients with a diagnosis of depression according to the CCMD-3 criteria were involved in this study;they were randomly divided into the venlafaxine group(n = 26) and the paroxetine group(n = 26) for 6 weeks.Effects and side effects were evaluated with HAMD,HAMA, CGI-SI and TESS before and after the treatment.Results: Findings indicated that efficacy of venlafaxine was the similar to those of paroxetine.However,venlafaxine took effect more quickly and its side effects were less than paroxetine.Conclusions:Venlafaxine is an effective and safe antidepressant.It is suggested that venlafaxine could be used as a first-line antidepressant in the treatment of depression for the elder.
Paroxetine
Depression
Venlafaxine Hydrochloride
Cite
Citations (0)
The treatment guidelines for obsessive-compulsive disorder (OCD) propose to switch serotonin reuptake inhibitors (SRIs) in case of refractoriness. However, no controlled research has been published yet that prospectively examined the effects of changing SRIs. This article describes the first double-blind switch study of 2 SRIs in patients with OCD.150 patients with primary OCD, according to DSM-IV criteria, were randomly assigned in a 12-week, double-blind trial to receive dosages titrated upward to 300 mg/day of venlafaxine (N = 75) or 60 mg/day of paroxetine (N = 75). Primary efficacy was assessed by the change from baseline on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), and nonresponse was defined as less than 25% reduction on the Y-BOCS. After a 4-week tapering phase, 43 nonresponders were switched to 12 additional weeks of the alternate antidepressant, of which 16 patients received venlafaxine and 27 received paroxetine.Eighteen of 43 patients benefited from a switch to the alternate SRI with a mean +/- SD decrease of at least 25% on the Y-BOCS. At the end of 12 weeks, responder rates were 56% for paroxetine (15/27) and 19% for venlafaxine (3/16). An intent-to-treat, last-observation-carried-forward analysis demonstrated a mean decrease on the Y-BOCS of 1.8 +/- 3.5 in the venlafaxine group and 6.5 +/- 7.1 in the paroxetine group. After 2 consecutive SRI trials, 109 of 150 patients (73%) achieved a Y-BOCS decrease of at least 25%.The results of the current study show that 42% of the nonresponders benefited from a crossover to the other SRI, and that paroxetine was more efficacious than venlafaxine in the treatment of nonresponders to a previous SRI trial. Switching SRIs in case of refractoriness may be considered a useful strategy for patients with OCD.
Paroxetine
Venlafaxine Hydrochloride
Serotonin reuptake inhibitor
Cite
Citations (133)
Objective: To study the efficacy and safety of venlafaxine extended-release and paroxetine on major depression( MD). Method: Application of stochastic methods,57 MD patients were randomed divided into venlafaxine extended-release group( 28 cases) and paroxetine group( 29 cases),and treated with corresponding antidepressant for 6 weeks. The patients were assessed by Hamilton depression rating scale 17( HRSD) before treatment,3,7,10,14 d and 6 weeks after treatment respectively. The side effect was assessed with treatment emergent symptom scale( TESS) at 3,7,10 and 14 d after treatment. Results: Fourteen day after treatment, there was interaction between group and time( F = 6. 608,P = 0. 001). Compared with before treatment,the scores of HRSD in venlafaxine extended-release group since 7 d and in paroxetine group since 10 d after treatment were significantly decreated( all P 0. 01). The HRSD scores in venlafaxine extended-release group were significant lower than paroxetine group at 7 and 14 d after treatment( all P 0. 01). Between the two groups the efficacy and side effects were no significant difference through 6 weeks treatment. Conclusion: Compare with paroxetine, venlafaxine extended-release works fast,but the curative effect and adverse reactions are equivalen on MD.
Paroxetine
Depression
Venlafaxine Hydrochloride
Cite
Citations (0)
1. Venlafaxine is an antidepressant agent which blocks in vitro the reuptake of both 5-HT and NA. The present in vivo electrophysiological studies were undertaken, in the rat, to compare the effects of venlafaxine on 5-HT and NA reuptake to those of the selective 5-HT reuptake inhibitor paroxetine and the selective NA reuptake inhibitor desipramine. 2. Administered acutely, venlafaxine dose-dependently prolonged the time required for a 50% recovery (RT50) of the firing activity of dorsal hippocampus CA3 pyramidal neurons from the suppression induced by microiontophoretic applications of 5-HT and NA. Venlafaxine and paroxetine increased with a similar potency the RT50 values for 5-HT, while desipramine was more potent than venlafaxine at increasing the RT50 values for NA. Moreover, venlafaxine demonstrated a greater potency at increasing the RT50 values for 5-HT compared to that of NA. 3. A two-day treatment with venlafaxine (delivered s.c. by osmotic minipumps) increased the RT50 values for both 5-HT and NA applications. The RT50 values for 5-HT were significantly increased at a dose of 10 mg kg(-1) day(-1), whereas those for NA were increased at a dose of 20 mg kg(-1) day(-1), consistent with the data obtained following the acute administration of venlafaxine. 4. Taken together, these results indicate that, in vivo, venlafaxine blocks both reuptake processes, with a potency greater for the 5-HT than for the NA reuptake process. This dual action, combined with the differential potency of venlafaxine, might constitute the biological substratum responsible for its apparent unique clinical efficacy in major depression.
Desipramine
Reuptake
Paroxetine
Venlafaxine Hydrochloride
Serotonin Uptake Inhibitors
Cite
Citations (56)
Article AbstractBackground: While selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment of obsessive-compulsive disorder (OCD), approximately 40% of patients fail to respond to SSRIs. Venlafaxine is a serotonin-norepinephrine reuptake inhibitor (SNRI) that might be effective in the treatment of OCD, even among those who have failed previous SSRI trials. Method: Thirty-nine patients who met DSM-IV criteria for OCD, including 29 who were resistant to prior SRI treatment trials, were treated with venlafaxine in an open, naturalistic fashion. Improvement was assessed using the Clinical Global Impressions-Improvement scale. Results: Of 39 patients treated with venlafaxine, 27 (69.2%) were rated as sustained treatment responders. Of the 29 patients who did not respond to 1 or more previous SRI trials, 22 (75.9%) were rated as having sustained response to treatment. Mean dose of venlafaxine was 232.2 mg/day (range, 37.5-375 mg/day), and it was generally well tolerated. Conclusion: Venlafaxine may be beneficial to individuals with OCD, including those who have not responded to prior SSRI trials. However, these findings must be interpreted with caution, as the study is limited by its open, retrospective nature and its inclusion of patients with comorbid diagnoses and patients on concomitant medications. Prospective, controlled trials with a more homogeneous patient population are needed to replicate these preliminary findings.
Venlafaxine Hydrochloride
Concomitant
Serotonin reuptake inhibitor
Cite
Citations (66)
Objective: To evaluate data supporting the ability of venlafaxine, an antidepressant with a dual mechanism of action, to produce remission from depression. Method: Review of multicentre, double‐blind, randomized studies comparing venlafaxine or venlafaxine extended release (XR) with a selective serotonin reuptake inhibitor (SSRI), using Hamilton Depression Rating Scale total scores in the range of ≤7 and <10 as the final outcome measure, to evaluate the ability of venlafaxine/venlafaxine XR to produce full remission from depression. Results: Venlafaxine/venlafaxine XR demonstrated higher rates of remission than did the SSRIs and placebo. Conclusion: With full remission rather than response as the measure of outcome, venlafaxine/venlafaxine XR demonstrated more robust antidepressant efficacy than the SSRIs and placebo. This finding suggests that venlafaxine/venlafaxine XR are appropriate standard‐of‐care therapies for the treatment of patients with major depressive disorder.
Venlafaxine Hydrochloride
Depression
Cite
Citations (32)
Paroxetine
Norepinephrine transporter
Venlafaxine Hydrochloride
Cite
Citations (63)
The authors report the CYP2D6 inhibitory effects of fluoxetine, paroxetine, sertraline, and venlafaxine in an open‐label, multiple‐dose, crossover design. Twelve CYP2D6 extensive metabolizers were phenotyped, using the dextromethorphan/dextrorphan (DM/DX) urinary ratio, before and after administration of fluoxetine 60 mg (loading dose strategy), paroxetine 20 mg, sertraline 100 mg, and venlafaxine 150 mg. Paroxetine, sertraline, and venlafaxine sequences were randomized with 2‐week washouts between treatments; fluoxetine was the last antidepressant (AD) administered. Comparing within groups, baseline DM/DX ratios (0.017) were significantly lower than DM/DX ratios after treatment (DM/DX AD ) with fluoxetine (0.313 , p < 0.0001) and paroxetine (0.601 , p < 0.0001) but not for sertraline (0.026 , p = 0.066) or venlafaxine (0.023 , p = 0.485). Between groups, DM/DX AD ratios were significantly higher for fluoxetine and paroxetine compared to sertraline and venlafaxine. No differences between DM/DX AD ratios were found for fluoxetine and paroxetine although more subjects phenocopied to PM status after receiving the latter (42% vs. 83%; χ 2 = 4.44, p = 0.049 , df = 1). Similarly, no differences between DM/DX AD ratios were found for sertraline and venlafaxine. Of note, the DM/DX AD for 1 subject was much lower after treatment with paroxetine (0.058) compared to fluoxetine (0.490), while another subject exhibited a much lower ratio after treatment with fluoxetine (0.095) compared to paroxetine (0.397). Significant correlations between AD plasma concentration and DM/DX AD were found for paroxetine ( r 2 = 0.404 , p = 0.026) and sertraline ( r 2 = 0.64 , p = 0.002) but not fluoxetine or venlafaxine. In addition, DM/DX AD correlated with baseline isoenzyme activity for paroxetine, sertraline, and venlafaxine groups. These results demonstrate the potent, but variable, CYP2D6 inhibition of fluoxetine and paroxetine compared to sertraline and venlafaxine. CYP2D6 inhibition may be related, in part, to dose, plasma concentration, and baseline isoenzyme activity, and these correlations merit further investigation .
Paroxetine
Sertraline
Venlafaxine Hydrochloride
Crossover study
Cite
Citations (128)