PEP Topic 
Peripheral Neuropathy

Lamotrigine is an anticonvulsant that inhibits the function of neuronal sodium channels, decreasing the release of excitatory neurotransmitters. Lamotrigine has been evaluated for the management of peripheral neuropathy and neuropathic pain. It is available as a tablet, extended release tablet, chewable tablet, and an orally dissolving tablet.

Effectiveness Unlikely

Research Evidence Summaries

Rao, R.D., Flynn, P.J., Sloan, J.A., Wong, G.Y., Novotny, P., Johnson, D.B., . . . Loprinzi, C.L. (2008). Efficacy of lamotrigine in the management of chemotherapy-induced peripheral neuropathy: A phase 3 randomized, double blind, placebo-controlled trial, N01C3. Cancer, 112, 2802–2808.

doi: 10.1002/cncr.23482

Intervention Characteristics/Basic Study Process:

Patients were randomized to either lamotrigine or placebo. Sixty-three patients were randomized to lamotrigine and 62 to placebo. The dose was escalated from 25 mg at bedtime to 150 mg twice daily, a regimen that continued for two weeks. Ten weeks after drug initiation, patients tapered off lamotrigine or placebo over a four-week period.

Sample Characteristics:

  • The study had a total sample size of 125 patients.
  • Patients were treated with neurotoxic chemotherapy.
  • Patients were symptomatic for chemotherapy-induced peripheral neuropathy for one month or more, with a daily average pain score of 4 or greater on a 10-point scale or greater than 1 on the Eastern Cooperative Oncology Group Grading Scale for CIPN.

Study Design:

Phase III randomized, double-blind, placebo-controlled trial

Measurement Instruments/Methods:

  • Investigators conducted assessments weekly. A numeric rating scale measured average daily pain scores.
  • Secondary measures included the World Health Organization Classification Scale, which rated neuropathy symptoms from 0 (none) to 4 (paralysis).
  • The Short-Form McGill Pain questionnaire assessed characteristics of pain (throbbing, stabbing, etc.).
  • The Brief Pain Inventory (Short Form) assessed the effect of pain on functional ability.
  • The Subjective Global Assessment measured change in overall symptoms from no change to much worse.
  • The Symptom Distress Scale, a five-point scale, measured common cancer-related symptoms.
  • The Profile of Mood States Short Form, a 30-item scale, measured mood states.
  • A single-item tool with a scale 0–100 measured quality of life.
  • The Eastern Cooperative Oncology Group Grading Scale for CIPN, a 10-point scale, measured specific pain qualities.
  • Investigators used National Cancer Institute common toxicity criteria to grade toxicity.


A total of 125 patients enrolled, but only 80 completed the study. Authors observed no significant differences between the two groups in the pain scale or the ENS.


Lamotrigine was not effective in relieving chemotherapy-induced peripheral neuropathy.


  • The sample was mixed, including different levels of chemotherapy-induced peripheral neuropathy, cancer treatments received, cancer diagnoses, and length of time since treatment completion.
  • Many primary and secondary outcomes were tested.
  • Authors did not account for the use of an error rate of only 2.5% or for stratification procedures by type of neurotoxic regimen. Sampling estimations increased the chance of statistical error.