From the Guidelines
Pregabalin is the most useful medication for peripheral neuropathy, as it has been extensively studied and shown to have favorable effects on pain improvement, with a majority of studies reporting at least 30-50% improvement in pain. According to the most recent and highest quality study 1, pregabalin is the most extensively studied drug for diabetic peripheral neuropathy (DPN) and has shown efficacy in reducing pain. The study recommends starting with a low dose and gradually increasing it to minimize adverse effects, which may be more severe in older patients.
The medication works by modulating calcium channels in the nervous system, reducing abnormal pain signaling that occurs in neuropathy. The typical starting dose is 75mg twice daily, potentially increasing to 300-600mg daily divided into two or three doses.
Other alternatives for patients who do not respond adequately to pregabalin include:
- Duloxetine (Cymbalta) 60mg daily, which has also shown efficacy in treating pain associated with DPN
- Gabapentin, which may be less expensive but is not FDA approved for this indication
- Tapentadol, a centrally acting opioid analgesic that has been approved by the FDA for the treatment of neuropathic pain associated with diabetes
It is essential to continue treatment for at least 2-4 weeks at an adequate dose before determining effectiveness and to monitor patients for side effects such as dizziness, drowsiness, and edema, which often improve with time or dose adjustment. Topical treatments like lidocaine patches or capsaicin cream can provide localized relief with fewer systemic side effects.
Key considerations when prescribing these medications include:
- Starting with low doses and gradually increasing to minimize adverse effects
- Monitoring patients for side effects and adjusting the dose as needed
- Considering the patient's presentation and comorbidities when selecting a treatment
- Using a tailored and stepwise pharmacological strategy to achieve pain reduction and improve quality of life, as recommended by 1.
From the FDA Drug Label
The efficacy of the maximum recommended dose of pregabalin for the management of neuropathic pain associated with diabetic peripheral neuropathy was established in three double-blind, placebo-controlled, multicenter studies The efficacy of duloxetine delayed-release capsules for the management of neuropathic pain associated with diabetic peripheral neuropathy in adults was established in 2 randomized, 12-week, double-blind, placebo-controlled, fixed-dose trials
The most useful medication for peripheral neuropathy is not explicitly stated in the provided drug labels. Both pregabalin and duloxetine have been shown to be effective in managing neuropathic pain associated with diabetic peripheral neuropathy.
- Pregabalin was studied in three double-blind, placebo-controlled, multicenter studies, with doses of 100 and 200 mg three times a day showing statistically significant improvement in endpoint mean pain score and increased proportion of patients with at least a 50% reduction in pain score from baseline 2.
- Duloxetine was studied in two randomized, 12-week, double-blind, placebo-controlled, fixed-dose trials, with doses of 60 mg once daily or 60 mg twice daily showing statistically significant improvement in endpoint mean pain scores from baseline and increased proportion of patients with at least a 50% reduction in pain scores from baseline 3. However, the provided information does not allow for a direct comparison between the two medications to determine which one is more useful.
From the Research
Medications for Peripheral Neuropathy
The following medications are commonly used to treat peripheral neuropathy:
- Selective serotonin-norepinephrine reuptake inhibitors (SNRIs) such as duloxetine and venlafaxine 4, 5
- Gabapentin 4, 5
- Tricyclic antidepressants 4, 5, 6
- Topical lidocaine and transcutaneous electrical nerve stimulation, specifically for focal peripheral neuropathic pain 4, 5
- Pregabalin, as a first-line treatment according to international guidelines, but second-line in the more recent French guidelines 4, 5
- Tramadol, combination therapies, and psychotherapy as adjuncts, proposed as second-line treatments 4, 5
- High-concentration capsaicin patches and botulinum toxin A, proposed specifically for focal peripheral neuropathic pain 4, 5
Comparison of Medications
Studies have compared the efficacy of different medications for peripheral neuropathy:
- A multicentre, double-blind, randomised crossover trial found that amitriptyline supplemented with pregabalin, pregabalin supplemented with amitriptyline, and duloxetine supplemented with pregabalin had similar analgesic efficacy 7
- A comparative, prospective, observational study found that amitriptyline, pregabalin, and duloxetine were all associated with adequate pain reduction, but amitriptyline had more favorable findings with tolerable side effects 8
- A review of pharmacotherapy for neuropathic pain found that tricyclic antidepressants tend to work better than gabapentin and other treatment options, while serotonin noradrenaline reuptake inhibitors appear to be equally effective 6
Side Effects
Common side effects of medications for peripheral neuropathy include: