Desvenlafaxine

Desvenlafaxine is a serotonin (5-HT) and norepinephrine (NE) reuptake inhibitor with K_i of 40.2 nM and 558.4 nM, respectively.

Efficacy of Desvenlafaxine Compared With Placebo in Major Depressive Disorder Patients by Age Group and Severity of Depression at Baseline.[Pubmed:28146000]

J Clin Psychopharmacol. 2017 Apr;37(2):182-192.

PURPOSE: This post hoc meta-analysis evaluated the efficacy and safety of Desvenlafaxine 50 and 100 mg versus placebo across age groups and severity of depression at baseline in patients with major depressive disorder. METHODS: Data from placebo and Desvenlafaxine 50-mg and 100-mg dose arms were pooled from 9 short-term, placebo-controlled, major depressive disorder studies (N = 4279). Effects of age (18-40 years, >40 to <55 years, 55-<65 years, and >/=65 years) and baseline depression severity (mild, 17-item Hamilton Rating Scale for Depression total score [HAM-D17] 18 to <25; severe, HAM-D17 >/=25) on Desvenlafaxine efficacy were assessed using analysis of covariance for continuous end points and logistic regression for categorical end points. FINDINGS: Desvenlafaxine-treated (50 or 100 mg/d) patients had significantly (P < 0.05, 2-sided) greater improvement in most measures of depression and function compared with placebo for patients 18 to 40 years, older than 40 to younger than 55 years, and 55 to younger than 65 years, with no significant evidence of an effect of age. Desvenlafaxine significantly improved most measures of depression and function in moderately and severely depressed patients. There was a significant baseline severity by treatment interaction for HAM-D17 total score only (P = 0.027), with a larger treatment effect for the severely depressed group. IMPLICATIONS: Desvenlafaxine significantly improved depressive symptoms in patients younger than 65 years and in patients with moderate or severe baseline depression. Sample sizes were not adequate to assess Desvenlafaxine efficacy in patients 65 years or older or with mild baseline depression.

[Desvenlafaxine and neuropathic pain: additional clinical benefits of a second generation serotonin-noradrenaline reuptake inhibitor].[Pubmed:28229443]

Rev Neurol. 2017 Mar 1;64(5):219-226.

INTRODUCTION: Desvenlafaxine is the third antidepressant within the group of serotonin-norepinephrine reuptake inhibitors. The latest clinical practice guidelines consulted agree that tricyclic antidepressants, dual (venlafaxine/duloxetine) and gabapentin/pregabalin antiepileptics, are the first-line drugs in the treatment of neuropathic pain, being tramadol, lidocaine 5% patches and capsaicin 8% patches of second-line drugs, while strong opioids constitute a third line treatment. The interaction between the binomial pain and depression is very frequent, being the psychological complication more frequent in patients with chronic pain. DEVELOPMENT: Following a literature search, this article summarizes the most relevant pharmacological data of Desvenlafaxine and its usefulness in clinical practice, as well as the specific literature of this drug in neuropathic pain and chronic pain. CONCLUSIONS: Although evidence of Desvenlafaxine in neuropathic pain is scarce, it presents some interesting pharmacokinetic properties, as it is not substrate or have activity on P-glycoprotein, and have a metabolism which practically does not depend on cytochrome P450 system, which limits the risk of pharmacokinetic interactions and potential problems associated tolerability when administered with drugs that are CYP2D6 moderate or potent inhibitors or other substrates of this isoenzyme. These characteristics make Desvenlafaxine a different antidepressant especially useful in some subgroups of patients with chronic pain (as polypharmacy and patients with liver failure), where comorbid depression is frequent.

Spectroscopic exploration and thermodynamic characterization of desvenlafaxine interacting with fluorescent bovine serum albumin.[Pubmed:27696548]

J Mol Recognit. 2017 Feb;30(2).

The mechanism of the interaction between bovine serum albumin (BSA) and Desvenlafaxine was studied using fluorescence, ultraviolet absorption, 3-dimensional fluorescence spectroscopy, circular dichroism, synchronous fluorescence spectroscopy, cyclic voltametry, differential scanning calorimetry, and attenuated total reflection-Fourier transform infrared spectroscopic techniques under physiological condition at pH 7.4. Stern-Volmer calculations authenticate the fluorescence of BSA that was quenched by Desvenlafaxine in a collision quenching mode. The fluorescence quenching method was used to evaluate number of binding sites "n" and binding constant KA that were measured, and various thermodynamic parameters were evaluated at different temperatures by using the van't Hoff equation and differential scanning calorimetry technique, which indicated a spontaneous and hydrophobic interaction between BSA and Desvenlafaxine. According to the Forster theory we calculate the distance between the donor, BSA and acceptor, Desvenlafaxine molecules. Furthermore, circular dichroism and attenuated total reflection-Fourier transform infrared spectroscopy indicate nominal changes in the secondary structure of the protein.

Concordance between actual and pharmacogenetic predicted desvenlafaxine dose needed to achieve remission in major depressive disorder: a 10-week open-label study.[Pubmed:27779571]

Pharmacogenet Genomics. 2017 Jan;27(1):1-6.

BACKGROUND: Pharmacogenetic-based dosing support tools have been developed to personalize antidepressant-prescribing practice. However, the clinical validity of these tools has not been adequately tested, particularly for specific antidepressants. OBJECTIVE: To examine the concordance between the actual dose and a polygene pharmacogenetic predicted dose of Desvenlafaxine needed to achieve symptom remission. MATERIALS AND METHODS: A 10-week, open-label, prospective trial of Desvenlafaxine among Caucasian adults with major depressive disorder (n=119) was conducted. Dose was clinically adjusted and at the completion of the trial, the clinical dose needed to achieve remission was compared with the predicted dose needed to achieve remission. RESULTS: Among remitters (n=95), there was a strong concordance (Kendall's tau-b=0.84, P=0.0001; Cohen's kappa=0.82, P=0.0001) between the actual and the predicted dose need to achieve symptom remission, showing high sensitivity (>/=85%), specificity (>/=86%), and accuracy (>/=89%) of the tool. CONCLUSION: Findings provide initial evidence for the clinical validity of a polygene pharmacogenetic-based tool for Desvenlafaxine dosing.