Venlafaxine

Pharmacokinetics of venlafaxine in treatment responders and non-responders: a retrospective analysis of a large naturalistic database.[Pubmed:30968172]

Eur J Clin Pharmacol. 2019 Apr 9. pii: 10.1007/s00228-019-02675-4.

PURPOSE: To assess in a large naturalistic sample, whether clinical response to a treatment with Venlafaxine is associated with different patterns of plasma concentrations of active moiety, AM (sum of Venlafaxine (VEN) and its active metabolite O-desmethylVenlafaxine (ODVEN)). METHODS: Applying a regression model, plasma concentrations and plasma concentrations corrected-by-dosage (C/D) for AM were included as independent variable with Clinical Global Impressions-Improvement (CGI-I) scale ratings as dependent variable. Moreover, AM, VEN, and ODVEN were compared between treatment responders and non-responders, defining response as much or very much improved on the CGI-I scale based on the non-parametric Mann-Whitney U (M-W-U) test with a significance level of 0.05. RESULTS: No correlations were found between AM and C/D AM plasma concentrations and CGI-I ratings (regression coefficient 0.0, CI 0.000, 0.001, p = 0.492 for AM and 0.047, CI - 0.065, 0.159, p = 0.408 for C/D AM). Venlafaxine daily dosage did not differ between responders and non-responders (217.7 +/- 76.9 vs. 222.0 +/- 72.7 mg/day, p = 0.45 for M-W-U). Responders displayed lower ODVEN (p = 0.033) and AM (p = 0.031) plasma concentrations than non-responders (p = 0.033 and 0.031, respectively for M-W-U). No other differences were detected. Using a cut-off level of 400 ng/mL for AM concentrations, a higher percentage of responders was reported in the group of patients with AM < 400 ng/mL (13.04%) compared to patients with AM > 400 ng/mL (8%) (p = 0.038). CONCLUSIONS: Higher ODVEN and AM concentrations in non-responders than in responders indicate that treatment escalation above upper thresholds of therapeutic reference ranges of Venlafaxine is not promising. Hence, the therapeutic reference range for Venlafaxine can help in improving outcomes in a measurement-based care model that takes advantage of therapeutic drug monitoring.

Role of venlafaxine in relapse to methamphetamine seeking. Potential treatment option for drug dependence.[Pubmed:30957126]

Saudi Med J. 2019 Apr;40(4):339-346.

OBJECTIVES: To investigate the effects of Venlafaxine (VEN) on the relapse of methamphetamine (METH)-induced conditioned place preference (CPP) in rats. METHODS: This study was conducted at the Department of Pharmacology and Toxicology, and the Addiction and Neuroscience Research Unit, College of Pharmacy, Taif University, Taif, Kingdom of Saudi Arabia between May 2017 and October 2018. A total of 32 male Wistar rats were used in this study. Rats were divided to receive either METH or saline during the conditioning phase. Following the acquisition of METH-induced CPP, the animals were randomly divided to receive saline or VEN for 21 days instead of METH during the extinction training. The reinstatement was initiated by re-exposure to a single dose of METH to test any anti-reinstatement effects of VEN. Results: Two-way repeated measures Analysis of Variance (ANOVA) (time x chamber) was used to analyze time spent in conditioning chambers, while distance traveled was analyzed using one-way ANOVA. Saline or VEN, when administered alone, did not affect CPP or locomotor activity results. A priming intraperitoneal injection of METH reinstated CPP in the animals treated with saline during the extinction phase. Interestingly, VEN treatment blocked METH-induced CPP. CONCLUSION: Venlafaxine effects on the reinstatement of METH-induced CPP are not likely due to nonspecific effects on locomotor activity. This beneficial effect of VEN on relapse to METH-induced CPP could be due to its antidepressant effects. Venlafaxine can thus be a potential therapeutic option in the treatment of relapse to METH-seeking behaviors.

The Course of Adverse Events in Venlafaxine XR Treatment in Generalized Anxiety Disorder.[Pubmed:30932946]

J Clin Psychopharmacol. 2019 Mar 29.

PURPOSE: The time course of adverse events is an important factor for patient management. Clinicians are better able to prepare patients for specific adverse events, which leads to better treatment adherence. METHODS: Adverse events were followed longitudinally for 6 months during the open-label phase of a relapse prevention trial with 264 patients with generalized anxiety disorder. Adverse events were assessed at each treatment visit using a 21-item checklist. Logistic regression modeling, continuation ratio modeling, and hierarchical linear modeling were used to determine whether adverse events led to early attrition and whether adverse events decreased in enrolled patients over time. FINDINGS: Adverse events were found to have decreased highly significantly during treatment. A highly significant race effect was found in that whites had a significantly higher adverse event rate than did nonwhites. Early attrition rates were predicted by presence of nausea and fatigue, late attrition by dizziness, nervousness, and sexual dysfunction. IMPLICATIONS: Our findings provide information for clinicians on the course of adverse events over treatment, useful to prepare patients for treatment adherence.

Effect of Sertraline, Dosulepin, and Venlafaxine on Non-BDNF Neurotrophins in Patients With Depression: A Cohort Study.[Pubmed:30932945]

J Clin Psychopharmacol. 2019 Mar 29.

BACKGROUND: The neurotrophic hypothesis of depression has been mostly studied with a focus on brain-derived neurotrophic factor (BDNF) leading to lack of data on non-BDNF neurotrophins (NTs). The aim of this study was to evaluate the effect of antidepressant drugs on changes in serum nerve growth factor (NGF), neurotrophin 3 (NT-3), and neurotrophin 4 (NT-4). METHODS: A prospective cohort study was conducted on 105 patients with depression who were subgrouped to the group 1 (mild and moderate depression without somatic syndrome treated with sertraline), group 2 (mild and moderate depression with somatic syndrome treated with dosulepin), and group 3 (severe depression without psychotic symptoms treated with Venlafaxine). At baseline, the severity of depression (Montgomery-Asberg Depression Rating Scale [MADRS]), serum NGF, NT-3, and NT-4 were estimated. Thirty-five healthy volunteers were recruited as controls for a baseline comparison of NTs. All patients were followed up after 6 weeks to evaluate the changes in NT levels and correlate it with the change in MADRS scores. RESULTS: At baseline, NT levels were significantly lower in patients with depression in comparison with healthy control. In group 1, serum NGF, NT-3, and NT-4 level were found to increase significantly after treatment, whereas changes in groups 2 and 3 were statistically not significant. Montgomery-Asberg Depression Rating Scale score and serum NGF at baseline had an inverse relation (r = -0.648), whereas the change in MADRS score in sertraline group had a positive correlation (r = 0.86) with the change of serum NGF. CONCLUSIONS: Monotherapy with sertraline increased the level of non-BDNF NTs; however, treatment with dosulepin and Venlafaxine did not produce any significant changes in patients with depression.

Venlafaxine alleviates complete Freund's adjuvant-induced arthritis in rats: Modulation of STAT-3/IL-17/RANKL axis.[Pubmed:30928406]

Life Sci. 2019 Mar 27. pii: S0024-3205(19)30227-9.

AIMS: Rheumatoid arthritis is usually accompanied by various comorbidities especially on the psychological side such as depression. This study aimed at revealing the potential curative effects of Venlafaxine (VFX), a serotonin/norepinephrine reuptake inhibitor (SNRI), on experimentally-induced arthritis in rats. METHODS: Arthritis was induced by injecting complete Freund's adjuvant (CFA, 0.1ml, s.c.). One day thereafter, VFX (50mg/kg, p.o.) was given for 21days. Methotrexate was used as a standard disease modifying anti-rheumatic drug. KEY FINDINGS: CFA injection caused prominent arthritis evident by the increase in the hind paw and ankle diameter accompanied by elevating tumor necrosis factor-alpha, interleukin-6, interleukin-17 and matrix metalloproteinase-3 levels, effects that were diminished by VFX. Moreover, VFX down regulated gene expressions of receptor activator of nuclear factor kappa-B (NF-small ka, CyrillicB) ligand and signal transducer and activator of transcription-3 beside hampering immunohistochemical expression of vascular endothelial growth factor and NF-small ka, CyrillicB. This SNRI also improved the oxidant status of the hind limb as compared to the arthritic group. Nonetheless, MTX was better in amendment of arthritis authenticated by its effect on some inflammatory and oxidative stress biomarkers. SIGNIFICANCE: This study provides a novel therapeutic use of VFX as a considerable anti-arthritic drug and offers an incentive to expand its use in RA.