From the Guidelines
For patients with peripheral neuropathy who are allergic to gabapentin or pregabalin, duloxetine (30-60mg daily) is a recommended first-line alternative, as it has shown consistent efficacy in painful diabetic peripheral neuropathy, with effectiveness sustained for 1 year in an open-label trial 1. Other alternative treatment options include:
- Tricyclic antidepressants like amitriptyline (starting at 10-25mg at bedtime, gradually increasing to 25-150mg daily) or nortriptyline (10-25mg initially, up to 75mg daily)
- Serotonin-norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine (75-225mg daily)
- Topical treatments including lidocaine patches (5%, applied for up to 12 hours daily) or capsaicin cream (0.025-0.075%, applied 3-4 times daily) for localized neuropathic pain
- Opioids like tramadol (50-100mg every 4-6 hours) for short-term use in more severe cases, although they carry addiction risks
- Non-pharmacological approaches such as physical therapy, acupuncture, transcutaneous electrical nerve stimulation (TENS), and cognitive behavioral therapy to complement medication These alternatives work through different mechanisms, including modulating pain signals by increasing serotonin and norepinephrine, blocking local pain transmission, and improving function and pain perception through various pathways 1.
From the Research
Alternative Treatments for Peripheral Neuropathy
In patients allergic to gabapentin or pregabalin, several alternative treatments can be considered for peripheral neuropathy. These include:
- Tricyclic Antidepressants (TCAs): Such as amitriptyline, nortriptyline, desipramine, and imipramine, which have been shown to be effective for the symptomatic relief of post-herpetic neuralgia (PHN) and painful diabetic neuropathy (PDN) 2.
- Serotonin Noradrenaline Reuptake Inhibitors (SNRIs): Like venlafaxine and duloxetine, which have been shown to be effective for the treatment of PDN with fewer adverse effects than TCAs 2.
- Selective Serotonin Reuptake Inhibitors (SSRIs): Although results are conflicting, some studies suggest that SSRIs may have some efficacy in relieving PDN-related pain 2.
- Antiepileptic Agents: Such as carbamazepine, phenytoin, and valproic acid, which have been shown to be effective in ameliorating PDN-related pain 2. Other antiepileptic agents like lamotrigine, oxcarbazepine, and topiramate have also demonstrated some beneficial effects for the treatment of PDN.
- Opioids: Like oxycodone and tramadol, which have been shown to be superior to placebo for the treatment of PHN and PDN, although their use is controversial due to potential for abuse and addiction 2, 3.
- Topical Agents: Such as lidocaine 5% patches and topical capsaicin, which can be useful in ameliorating pain in patients with PHN, but are often unsatisfactory as a sole agent 2.
Combination Therapy
Combination therapy, using drugs that produce pain relief via distinctly different mechanisms, may be successful in patients who do not achieve satisfactory relief with monotherapy 2, 4. A study comparing amitriptyline supplemented with pregabalin, pregabalin supplemented with amitriptyline, and duloxetine supplemented with pregabalin found that combination treatment was well tolerated and led to improved pain relief in patients with suboptimal pain control with monotherapy 4.
Emerging Treatment Options
New and emerging treatment options for neuropathic pain include a wide range of compounds, such as N-methyl-D-aspartate receptor antagonists, cholecystokinin receptor antagonists, adenosine, lipoic acid, cannabinoids, and VR-1 receptor modulators 5. However, many of these compounds are limited by marginal efficacy and clinically significant adverse events, and few have been evaluated in well-controlled, large-scale clinical trials.