Compare medications for DIABETIC Neuropathy
Overview
Up to 50% of patients with diabetes develop peripheral neuropathy. Tailor medication selection based on side effects, cost, whether the medication can also treat other conditions, etc. Expect trial and error. Start at low doses and titrate to effect. But set realistic expectations. In general, fewer than 1 in 3 patients will see a 50% decrease in pain with first-line medications.
Medications
Tricyclics (TCAs)
Save these for younger patients or those without cardiovascular (CV) disease due to concerns about falls, hypotension, etc. Consider a TCA with fewer anticholinergic effects. For example, prescribe nortriptyline (Motival) at a starting dose of 10 to 25 mg/day, rather than amitriptyline (Tryptizol) or imipramine (Tofranil). USE Serotonin-Noradrenaline Reuptake Inhibitors (SNRIs), for patients who also have anxiety or depression, titrate duloxetine (Cymbalta, Cymbatex) up to 60 mg/day or venlafaxine (Efexor) up to 225 mg/day. SNRIs are linked to blood pressure increases and sexual side effects. But these seem less likely with lower SNRI doses or with duloxetine.
Gabapentinoids
Think of these as an option for patients who also have restless legs syndrome. Pregabalin (Lyrica) can be titrated up to 600 mg/day or gabapentin (Gaptin, Conventin) up to 3,600 mg/day, but monitor for side effects (dizziness, peripheral edema, etc). And gabapentinoid misuse continues to be a concern.
| Table (1). Drugs Approved by the FDA for Treatment of Neuropathic Pain | ||||
|---|---|---|---|---|
| Medication | Beginning Dosages | Titration | Maximum Dosage | Duration of Adequate Trial |
| Gabapentin | 100-300 mg every night or 100-300 mg 3×/day | Increase by 100-300 mg 3×/d every 1-7 days as tolerated | 3600 mg/day (1200 mg 3×/day); reduce if low creatinine clearance | 3-8 week for titration plus 1-2 week at maximum tolerated dosage |
| Pregabalin | 50 mg three times a day | Increase up to 100 mg three times a day | 600 mg a day | Start with 50mg TID and increase upto 100mg TID over 1 week |
| Lamotrigine | 200-400 mg every night. | Start with 25 to 50 mg every other day and increase by 25 mg every week | 500 mg a day | 3 to 5 week for titration ad 1 -2 week at maximum tolerated dosage |
| Carbamazepine | 200 mg/d (100 mg BID) | Add up to 200 mg/day in increments of 100 mg every 12 hr | 1200 mg/day | |
| Duloxetine | 30 mg | 30 mg weekly | 120 mg | 2 week |
| 5% lidocaine patch | Maximum of 3 patches daily for a maximum of 12 hr | None needed | Maximum of 3 patches daily for a maximum of 12 hr | 2 week |
| Opioid analgesics | 5-15 mg every 4 hr as needed | After 1-2 week, convert total daily dosage to long-acting medication as needed | No maximum with careful titration; consider evaluation by pain specialist at dosages exceeding 120-180 mg/day | 4-6 week |
| Tramadol hydrochloride | 50 mg 1 or 2×/day | Increased by 50-100 mg/day in divided doses every 3-7 days as tolerated | 400 mg/day (100 mg 4×/day); in patients older than 75 years, 300 mg/day in divided doses | 4 week |
| Tricyclic antidepressants (eg, nortriptyline hydrochloride or desipramine hydrochloride) | 10-25 mg every night | Increase by 10-25 mg/day every 3-7 days as tolerated | 75-150 mg/day; if blood level of active drug and its metabolite is < 100 ng/mL, continue titration with caution | 6-8 week with at least 1-2 week at maximum tolerated dosage |
| Duloxetine Serotonin/norepinephrine Reuptake inhibitor |
30 mg BID | Increase by 60 to 60 BID. No further titration | 120 mg/day | 4 week |
| Fluoxetine Serotonin/norepinephrine Reuptake inhibitor |
30 mg BID | Increase by 60 mg to 60 BID. No further titration | 120 mg/day | 4 week |
| Tapentadol ER | 50 mg BID | Increase by 50 mg/BID every 3 days as tolerated | 500 mg/day | |
| Reference: Vinik A, Casellini C, Nevoret ML. Diabetic Neuropathies. [Updated 2018 Feb 5]. In: Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Table 7, Drugs Approved by the FDA for Treatment of Neuropathic Pain Syndromes. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279175/table/diab-neuropathies.medication | ||||
Monitoring and other considerations
Reevaluate the medication after about 12 weeks at an optimized dose. If patients don’t respond, consider switching to a different first-line medication. Or with a partial response, try combining a TCA or SNRI plus a gabapentinoid, but watch for additive side effects.
- Consider topical capsaicin (Capsin cream) or lidocaine patches if oral medications aren’t an option or as an add-on. Evidence is more limited.
- If patients ask, explain that alpha-lipoic acid (Thiotacid) 600 to 1,800 mg/day might help, but to stop if there’s no benefit after a month or so.
- Avoid opioids, including tramadol (Tramal) or tapentadol (Nucynta, NOT available in Egypt), any benefits don’t outweigh risks (misuse, overdose, etc).
Reinforce glucose management, it may slow neuropathy progression. Keep in mind, metformin (Glucophage) is linked to vitamin B12 deficiency and worsening neuropathy. Check B12 levels if patients develop symptoms, or every 2 to 3 years for those at risk (older patients, vegetarians, etc). Recommend a B12 supplement if needed. And manage other conditions that may impact pain (insomnia, etc).
References
- Price R, Smith D, Franklin G, Gronseth G, Pignone M, David WS, Armon C, Perkins BA, Bril V, Rae-Grant A, Halperin J, Licking N, O'Brien MD, Wessels SR, MacGregor LC, Fink K, Harkless LB, Colbert L, Callaghan BC. Oral and Topical Treatment of Painful Diabetic Polyneuropathy: Practice Guideline Update Summary: Report of the AAN Guideline Subcommittee. Neurology. 2022 Jan 4;98(1):31-43.
- American Diabetes Association Professional Practice Committee; American Diabetes Association Professional Practice Committee:, Draznin B, Aroda VR, Bakris G, Benson G, Brown FM, Freeman R, Green J, Huang E, Isaacs D, Kahan S, Leon J, Lyons SK, Peters AL, Prahalad P, Reusch JEB, Young-Hyman D, Das S, Kosiborod M. 12. Retinopathy, Neuropathy, and Foot Care: Standards of Medical Care in Diabetes-2022. Diabetes Care. 2022 Jan 1;45(Supplement_1):S185-S194.
- Khdour MR. Treatment of diabetic peripheral neuropathy: a review. J Pharm Pharmacol. 2020 Jul;72(7):863-872.
- Jingxuan L, Litian M, Jianfang F. Different Drugs for the Treatment of Painful Diabetic Peripheral Neuropathy: A Meta-Analysis. Front Neurol. 2021 Oct 29;12:682244.
- Asrar MM, Kumari S, et al. Relative Efficacy and Safety of Pharmacotherapeutic Interventions for Diabetic Peripheral Neuropathy: A Systematic Review and Bayesian Network Meta-Analysis. Pain Physician. 2021 Jan;24(1):E1-E14.