desvenlafaxine-succinate and Neuralgia

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.. 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.. 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.. Desvenlafaxina y dolor neuropatico: beneficios clinicos adicionales de un inhibidor de la recaptacion de serotonina-noradrenalina de segunda generacion.. Introduccion. La desvenlafaxina es el tercer antidepresivo incluido entre los inhibidores de la recaptacion de serotonina y noradrenalina. Las ultimas guias de practica clinica consultadas coinciden en señalar que los antidepresivos triciclicos, los duales (venlafaxina/duloxetina) y los antiepilepticos gabapentina y pregabalina constituyen los farmacos de primera linea en el tratamiento del dolor neuropatico. El tramadol, los apositos de lidocaina al 5% y los parches de capsaicina al 8% son los farmacos de segunda linea, mientras que los opioides potentes constituirian una tercera linea de tratamiento. La interaccion entre el binomio dolor y depresion es muy habitual y representa la complicacion psicologica mas frecuente en los pacientes con dolor cronico. Desarrollo. Tras una busqueda bibliografica, en este articulo se resumen los datos farmacologicos mas relevantes de la desvenlafaxina y su utilidad en la practica clinica, asi como la bibliografia especifica de este farmaco en el dolor neuropatico y el dolor cronico. Conclusiones. Aunque la evidencia de la desvenlafaxina en el dolor neuropatico es escasa, presenta unas caracteristicas farmacocineticas interesantes, como son no ser sustrato ni actuar sobre la glicoproteina P y tener un metabolismo que practicamente no depende del sistema del citocromo P450, lo que limita el riesgo de interacciones farmacocineticas y los potenciales problemas de tolerabilidad asociados cuando se administra con farmacos que sean inhibidores moderados o potentes del CYP2D6 o con otros sustratos de esta isoenzima. Estas caracteristicas hacen de la desvenlafaxina un antidepresivo distinto y especialmente util en algunos subgrupos de pacientes con dolor cronico (como polimedicados y pacientes con insuficiencia hepatica), donde la depresion comorbida es frecuente.

Topics: Antidepressive Agents; Biological Availability; Biotransformation; Chronic Pain; Clinical Trials as Topic; Cytochrome P-450 Enzyme System; Depressive Disorder; Desvenlafaxine Succinate; Dose-Response Relationship, Drug; Drug Interactions; Duloxetine Hydrochloride; Humans; Multicenter Studies as Topic; Neuralgia; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride

Amitriptyline effectively relieves neuropathic pain following treatment of breast cancer. However, adverse effects are a major problem. Venlafaxine has no anticholinergic effects and could have a better compliance. The aim of the study was to evaluate the effectiveness of venlafaxine in neuropathic pain. The study was a randomized, double-blind, crossover comparison of venlafaxine and inactive placebo. The study lasted 10 weeks. The number of tablets (18.75 mg) taken daily was increased by one at a 1 week interval. Pain intensity and pain relief were registered daily by a diary and by a questionnaire and a computer program (Painscreen) on each visit. Adverse effects were evaluated with the diaries and a 10-item list on each visit. Also, anxiety and depression were measured on each visit. Venous blood samples were collected before the treatment and at 4 weeks for the determination of the serum levels of venlafaxine and its three metabolites. Thirteen patients were analysed. The average daily pain intensity as reported in the diary (primary outcome) was not significantly reduced by venlafaxine compared with placebo. However, the average pain relief (diary) and the maximum pain intensity (retrospective assessment by the computer program) were significantly lower with venlafaxine compared with placebo. Anxiety and depression were not affected. Adverse effects did not show significant differences between treatments. The two poor responders had low venlafaxine concentrations whereas the two slow hydroxylizers had high venlafaxine concentrations and excellent pain relief. Thus, higher doses could be used in order to improve pain relief.

Topics: Analgesics; Breast Neoplasms; Cross-Over Studies; Cyclohexanols; Desvenlafaxine Succinate; Dose-Response Relationship, Drug; Female; Humans; Mastectomy; Neuralgia; Pain Measurement; Peripheral Nervous System Diseases; Postoperative Complications; Treatment Outcome; Venlafaxine Hydrochloride

Desvenlafaxine, a serotonin-norepinephrine reuptake inhibitor (SNRI) developed by Wyeth, is a novel salt form of the isolated major active metabolite of the antidepressant venlafaxine. Desvenlafaxine was developed as a slow-release tablet formulation and rapidly penetrates the brain upon administration supporting its direct effects on neuronal systems of the brain. Unlike various other antidepressants including venlafaxine, desvenlafaxine is not metabolized by cytochrome p450 (CYP) enzyme pathways and is associated with minimal inhibition of CYP enzymes. This feature results in a comparatively low risk of drug-drug interaction and consistent intra-individual and inter-individual pharmacokinetic profiles. Desvenlafaxine has been recently approved by the US FDA for the treatment of major depressive disorder (MDD) based on a series of randomized, double-blind, placebo-controlled clinical trials indicating efficacy and safety for patients with MDD. Studies have also supported the potential utility of desvenlafaxine in the treatment of vasomotor symptoms of menopause, anxiety symptoms and painful physical symptoms. However, concerns including mixed efficacy and adverse events need to be further explored in future studies.

Topics: Animals; Clinical Trials as Topic; Cyclohexanols; Depressive Disorder, Major; Desvenlafaxine Succinate; Female; Humans; Menopause; Molecular Structure; Neuralgia; Norepinephrine; Selective Serotonin Reuptake Inhibitors; Structure-Activity Relationship; Vasomotor System