Oral pharmacotherapeutics for the management of peripheral neuropathic pain conditions – a review of clinical trials

ABSTRACT

Introduction

Epidemiological studies have shown that 6.9–10% of people suffer from neuropathic pain, a complex painful condition which is often undertreated. Data regarding the effectiveness of treatment options for patients with neuropathic pain is inconsistent, and there is no single treatment option that shows cost-effectiveness across studies.

Areas covered

In this narrative review, the authors present the results of different prospective, randomized controlled trials, systematic reviews and meta-analyses assessing the effects of different oral medications in the management of various peripheral neuropathic pain conditions. The authors discuss the effectiveness of commonly used oral medications such as voltage-gated calcium channels antagonists, voltage-gated sodium channel antagonists, serotonin-norepinephrine reuptake inhibitors, NMDA antagonists, and medications with other mechanisms of action.

Expert opinion

Most of the presented medications were more effective than placebo; however, when compared to each other, none of them were significantly superior. The heterogeneity of the studies looking into different oral neuropathic conditions has been the major issue that prevents us from making stronger recommendations. There are multiple reasons including high placebo responsiveness, improperly treated underlying comorbidities (particularly anxiety and depression), and inter-patient variability. Different sensory phenotypes should also be taken into consideration when designing future clinical trials for neuropathic pain.

KEYWORDS:

• Peripheral neuropathic pain
• oral pharmacotherapy
• postherpetic neuralgia
• trigeminal neuralgia
• peripheral diabetic neuralgia
• chemotherapy-induced peripheral neuropathy

Article highlights

• Neuropathic pain is a complex, painful condition for which the available treatment options have inconsistent effectiveness.

• Tramadol and tapentadol should be approached carefully, due to their abuse potential, while NSAIDs, methadone, and cannabinoids were not shown to be effective in neuropathic pain treatment.

• For the treatment of PHN, effective drugs were shown to be gabapentin and amitriptyline.

• For the treatment of DPNP, effective drugs were shown to be gabapentin, mirogabalin, carbamazepine, duloxetine, and pregabalin.

• For the treatment of trigeminal neuralgia, carbamazepine, oxcarbazepine, and gabapentin were shown to be effective.

• In the future, neuropathic pain treatment strategies should be more personalized while keeping in mind the interpatient variability and other confounding variables (age, sex, comorbidities, etc.).

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One referee declares that they have patents on topical phenytoin for the treatment of chronic/neuropathic pain. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This manuscript was not funded.