Efficacy of Venlafaxine in Neuropathic Pain: A Narrative Review of Optimized Treatment

doi:10.1016/j.clinthera.2017.05.347

Clinical Therapeutics

Volume 39, Issue 6, June 2017, Pages 1104-1122

https://doi.org/10.1016/j.clinthera.2017.05.347 Get rights and content

Abstract

Purpose

The prevalence of neuropathic pain is high in the general population, and high priority is given to the management of this pain condition. The treatment of neuropathic pain remains challenging, despite the publication of national and international recommendations. The purpose of this narrative review of venlafaxine (VLX) is to provide a better knowledge of the pharmacology of this drug and a clearer view of its efficacy and tolerability in neuropathic pain.

Methods

Two independent reviewers searched PubMed with the following search terms: serotonin and noradrenalin reuptake inhibitors OR VLX hydrochloride AND pain. The reviewers included all clinical studies that investigated VLX in neuropathic pain conditions and excluded animal studies, studies on fibromyalgia, studies that focused on the prevention of neuropathic pain, case reports, and studies that did not clearly describe neuropathic pain in the included patients. We describe the 13 studies that we analyzed.

Findings

Eleven were randomized clinical trials, and the comparator was placebo in 8 studies. Nine studies reported that VLX was effective against neuropathic pain. However, among the trials, only one against placebo included a large number of patients with >200 participants and one against prégabaline and carbamazepine had >200 patients. Most of the adverse events reported in the selected studies were consistent with known adverse events of VLX, and most were mild to moderate. However, most studies were of very short duration.

Implications

Most of the clinical studies found that VLX was effective and well tolerated. However, given the limited number of study and the limitations of all these studies, further large clinical trials are needed. Currently, considering the limited therapeutic options for treating neuropathic pain and the highly variable nature of responses to all drugs, VLX has a place as a treatment option for neuropathic pain.

Introduction

The International Association for the Study of Pain defines neuropathic pain as “pain caused by a lesion or disease of the somatosensory nervous system.”¹ Its causes may be peripheral or central and include physical trauma, diabetes, postherpetic neuralgia, HIV-related neuropathy, spinal cord injury, and chemotherapy.² Patients experience diverse symptoms, including pain and altered sensations, that profoundly affect quality of life.³ Estimates of the prevalence of neuropathic pain range from 6.9% to 10% in the general population.4, 5, 6 The management of this condition is therefore considered of high priority. However, neuropathic pain is difficult to treat. Recommendations and guidelines have been developed for the optimization of treatment with the limited options currently available for this condition. Our poor understanding of the pathophysiologic processes underlying neuropathic pain and the limited usefulness of many of the pharmacologic agents currently available have made it difficult to develop effective treatment options for neuropathic pain.

This review focuses on the potential usefulness of venlafaxine (VLX) for treating neuropathic pain. This antidepressant has been widely used to treat pain, without support from pharmaceutical companies. A Cochrane review⁷ based on double-blind studies concluded that VLX was not effective for the treatment of neuropathic pain. However, several studies were absent from this analysis,8, 9, 10, 11, 12, 13, 14 and the negative conclusions of this meta-analysis are not consistent with current recommendations¹⁵ that VLX should be considered a first-line treatment. We therefore decided to perform a narrative review on VLX, including all studies on the use of this drug for the treatment of neuropathic pain, because a better knowledge of the pharmacology of this drug and of the studies performed to date might provide a clearer view of its efficacy and tolerability in neuropathic pain.

Section snippets

Pharmacodynamic Properties of VLX

Antidepressants and other psychotropic drugs have long been used to treat various pain syndromes, including migraine, fibromyalgia, and neuropathy.7, 16, 17, 18, 19 Many studies have found them to be useful for pain management, regardless of whether the patient has clinical symptoms of depression.7, 16, 17, 18, 19 Tricyclic antidepressants (TCAs) have the longest track record and are probably the group of psychotropic drugs most consistently effective for treating pain conditions.16, 17, 18, 19

Type of neuropathic pain

Five studies included patients with diabetic neuropathy.8, 9, 12, 47, 49 Three studies concerned patients with peripheral neuropathy.10, 45, 48 Two studies focused on patients with taxane- and oxaliplatin-induced neurotoxicity.11, 14 One study included patients with spinal cord injury.¹³ One study focused on patients with atypical neuropathic facial pain.⁴⁶ One study concerned patients with neuropathic pain after the treatment of breast cancer.⁴⁴

Design of the Studies

Ten studies were double-blind randomized clinical

Discussion and Conclusion

We reviewed the studies published to date dealing with the issue of the efficacy of VLX against neuropathic pain. We observed that VLX treatment yielded positive results in most trials. This finding is consistent with current guidelines, recommendations, and literature for neuropathic pain, confirming the importance of VLX as a treatment option.15, 51, 52, 53

VLX was recommended as a first-line treatment for neuropathic pain in the updated recommendations of the Neuropathic Pain Special Interest

Conflicts of Interest

The authors have indicated that they have no conflicts of interest regarding the content of this article.

Acknowledgments

A.-P. Trouvin and C. Lloret-Linares searched the literature and extracted data. A.P. Trouvin, S. Perrot, and C. Lloret-Linares analyzed and discussed the data. All authors reviewed and commented the manuscript. Only the 3 authors participated in writing and revising the manuscript. There was no monetary support of any kind.

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Review ArticleEfficacy of Venlafaxine in Neuropathic Pain: A Narrative Review of Optimized Treatment

Abstract

Purpose

Methods

Findings

Implications

Introduction

Section snippets

Pharmacodynamic Properties of VLX

Type of neuropathic pain

Design of the Studies

Discussion and Conclusion

Conflicts of Interest

Acknowledgments

Pain

Lancet Neurol

Pain

Pain

Pain

J Diabetes Complications

Ann Oncol

Arch Phys Med Rehab

Lancet Neurol

Pain

Neurobiol Dis

Brain Res

Eur J Pharmacol

Neurobiol Dis

J Pain Symptom Manage

Neuropsychopharmacology

Eur J Pain

Pain

Eur J Pain

Eur Psychiatry

Prevalence of Chronic Pain in the UK: A Systematic Review and Meta-Analysis of Population Studies

BMJ Open

Venlafaxine for Neuropathic Pain in Adults

Cochrane Database Syst Rev

Gabapentin and Venlafaxine for the Treatment of Painful Diabetic Neuropathy

J Clin Neuromuscul Dis

An Open-Label, Non-Randomized Comparison of Venlafaxine and Gabapentin as Monotherapy or Adjuvant Therapy in the Management of Neuropathic Pain in Patients with Peripheral Neuropathy

J Pain Res

Evaluation of the Efficacy and Safety of Pregabalin, Venlafaxine, and Carbamazepine in Patients with Painful Diabetic Peripheral Neuropathy. A Randomized, Double-Blind Trial

Neurosciences. (Riyadh)

Efficacy of Venlafaxine for the Relief of Taxane and Oxaliplatin-Induced Acute Neurotoxicity: A Single-Center Retrospective Case-Control Study

Support Care Cancer

Imipramine for Neuropathic Pain in Adults

Cochrane Database Syst Rev

Nortriptyline for Neuropathic Pain in Adults

Cochrane Database Syst Rev

Review Article
Efficacy of Venlafaxine in Neuropathic Pain: A Narrative Review of Optimized Treatment