This handout is for peripheral neuropathy (distal symmetric polyneuropathy — dspn; acquired-causes screen). Your care team identified this based on: distal symmetric numbness / tingling / "pins-and-needles" starting in toes ascending in a stocking distribution (length-dependent dspn — aan 2009 england pmid 19056666).
Other reasons your team may use this plan: burning / lancinating / electric distal pain, allodynia (small-fibre predominant; painful dspn — aan 2022 price pmid 34965987); sensory ataxia / imbalance / falls in the dark (large-fibre proprioceptive loss — route symptom.falls.v1); asymmetric / multifocal stepwise sensorimotor deficit (mononeuritis multiplex — vasculitic/diabetic/infiltrative — urgent).
Take these medications exactly as prescribed. Do not stop or change a dose without talking to your provider.
| Medication | Starting dose | How | When | What it does |
|---|---|---|---|---|
| pregabalin | 75 mg PO BID (start 25-75 mg HS in elderly/renal) | PO | BID | AAN 2022 Price 2022 PMID 34965987 first-line (level A for painful DPN); linear PK; anxiolytic/sleep benefit; special-population renal dose by CrCl: CrCl 30-60 → max 150-300 mg/day, CrCl 15-30 → max 75-150 mg/day, CrCl<15 → max 25-75 mg/day, supplemental dose after haemodialysis; geriatric — start 25-75 mg HS, sedation/oedema/fall risk (STOPP if falls); pregnancy — registry signal, avoid/specialist; opioid-combination respiratory-depression FDA warning |
| gabapentin | 300 mg PO HS, titrate to 300-1200 mg TID (start 100 mg HS elderly/renal) | PO | TID | AAN 2022 first-line; saturable absorption; lower cost; special-population renal dose by CrCl: CrCl 30-59 → 400-1400 mg/day divided, CrCl 15-29 → 200-700 mg/day, CrCl<15 → 100-300 mg/day, plus a post-dialysis supplemental dose; geriatric — start 100 mg HS, sedation/peripheral oedema/falls (STOPP); pregnancy/lactation — limited data, specialist; opioid-combination respiratory-depression FDA warning |
| duloxetine | 30 mg PO daily × 1 wk then 60 mg daily | PO | daily | AAN 2022 Price 2022 PMID 34965987 first-line; the ONLY agent with appropriate positive RCT evidence for established painful CIPN (ASCO 2020 Loprinzi PMID 32663120 — modest benefit, mean ~0.73-point reduction on 0-10 average-pain scale vs placebo; NO agent prevents CIPN); special-population: AVOID at eGFR<30 (renal — no dose that is safe) and in hepatic impairment / substantial alcohol use (hepatotoxicity); pregnancy — limited data, specialist risk-benefit; lactation — low relative infant dose but monitor; geriatric — start 30 mg, watch hyponatraemia/SIADH + falls; serotonin/BP/abrupt-withdrawal risk |
| amitriptyline | 10-25 mg PO HS, titrate by 10-25 mg q1-2 wk | PO | HS | AAN 2022 first-line (OPTION-DM Tesfaye 2022 PMID 36007534 — similar efficacy to pregabalin/duloxetine); special-population: CONTRAINDICATED in cardiac conduction disease/recent MI/QT prolongation; STOPP — explicitly avoid TCAs in older adults (anticholinergic burden → cognition, urinary retention, orthostatic falls); if a TCA is required in the elderly prefer nortriptyline/desipramine at the lowest dose; renal/hepatic — no specific cut-off but accumulation/sedation risk, go low-slow; pregnancy — most-studied TCA, specialist risk-benefit; baseline ECG if any cardiac risk |
| nortriptyline | 10-25 mg PO HS, titrate | PO | HS | Secondary-amine TCA — fewer anticholinergic/sedative effects than amitriptyline; preferred TCA in older adults when a TCA is chosen; same cardiac-conduction caution |
Plan: Neuropathic-pain pharmacotherapy — AAN 2022 painful DPN first-line classes (gabapentinoid / SNRI / TCA / Na-channel-blocker, similar efficacy — Price PMID 34965987; OPTION-DM Tesfaye 2022 PMID 36007534); comorbidity-driven selection; topical for localized; AVOID chronic opioids
Contact your care team if any of the following happen:
Call 911 or go to the nearest emergency room right away if you have:
Interval follow-up 4-12 wk during pain titration then per stability; foot-care + fall-prevention education; expect cause-treatment to stabilise (not always reverse) DSPN; re-investigate if progressive/atypical (re-phenotype — reconsider CIDP/vasculitis/paraneoplastic/amyloid); honest counselling on cryptogenic prognosis (generally slowly progressive, not life-limiting)
Guideline: AAN 2009 Practice Parameter — Evaluation of Distal Symmetric Polyneuropathy (laboratory/genetic testing; England) + AAN 2022 Oral & Topical Treatment of Painful Diabetic Polyneuropathy (Price) + ADA Standards of Care in Diabetes 2026 (Ch.12 Neuropathy/Foot Care) + EAN/PNS 2021 CIDP guideline (Van den Bergh) + EFNS/PNS skin-biopsy small-fibre neuropathy (Lauria) + ASCO 2020 CIPN guideline update (Loprinzi)