Charcot-Marie-Tooth Disease Medication

Updated: Feb 06, 2023
  • Author: Divakara Kedlaya, MBBS; Chief Editor: Vinod K Panchbhavi, MD, FACS, FAOA, FABOS, FAAOS  more...
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Medication Summary

Avoid drugs and medications known to cause nerve damage (eg, vincristine, [65] isoniazid, and nitrofurantoin). Identify the cause of any pain as accurately as possible. Musculoskeletal pain may respond to acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs). Neuropathic pain may respond to tricyclic antidepressants or antiepileptic drugs, such as carbamazepine or gabapentin.

Dyck et al, [66] as well as Ginsberg et al, [67] have described a few individuals with Charcot-Marie-Tooth (CMT) disease type 1 and sudden deterioration in whom treatment with steroids (prednisone) or intravenous immunoglobulin produced variable levels of improvement. Sahenk et al studied the effects of neurotrophin-3 on individuals with CMT 1A. [68]

Passage et al reported benefit from ascorbic acid (vitamin C) in a mouse model of CMT 1. [69]  However, in adult patients with symptomatic CMT 1A, Pareyson et al found that ascorbic acid supplementation (1.5 g/day) had no significant effect on neuropathy compared with placebo after 2 years, suggesting that no evidence supports treatment with ascorbic acid in adults with CMT 1A. [54]  A 2015 Cochrane review did not find evidence of benefit in adults or children. [70]

An exploratory randomized double-blind and placebo-controlled phase 2 study of a combination of baclofen, naltrexone and sorbitol (PXT3003) in patients with CMT 1A confirmed that PXT3003 was a safe and well-tolerated treatment for adults with this condition. [71] The trial enrolled 80 CMT 1A patients in France who were randomly assigned to a low, medium, or high dose of PXT3003 or a placebo for 12 months. On the basis of that result, the PLEO-CMT phase 3 trial (NCT02579759) was conducted.

PLEO-CMT was a 15-month double-blind study that assessed the efficacy and safety of two doses of PXT3003 as compared with placebo in 323 patients (age range, 16-65 years) with mild-to-moderate CMT 1A. It was conducted at 30 sites across the United States, the European Union, and Canada. PXT3003 was given twice daily (morning and evening) with food as a liquid formulation. The higher dose contained baclofen 12 mg, naltrexone 1.4 mg, and sorbitol 420 mg; the lower contained baclofen 6 mg, naltrexone 0.7 mg, and sorbitol 210 mg. Official study results have not been published as of early spring 2019; however, the study sponsor, Pharnext, states that PXT3003 consistently eased disability in these patients.

An animal study published in 2019 found that early short-term PXT3003 combinational therapy delayed disease onset in a transgenic rat model of CMT 1A. [72] These results may suggest that PXT3003 therapy may be a bona fide option for children and young adolescent patients suffering from CMT 1A.


Nonsteroidal anti-inflammatory drugs

Class Summary

Have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action is not known, but they may inhibit cyclooxygenase (COX) activity and prostaglandin synthesis. Other mechanisms may exist as well, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell membrane functions.

Ibuprofen (Motrin, Ibuprin)

DOC for patients with mild to moderate pain. Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.

Naproxen (Naprelan, Naprosyn, Anaprox)

For relief of mild to moderate pain; inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which results in a decrease of prostaglandin synthesis.


Cyclooxygenase-2 inhibitors

Class Summary

Although increased cost can be a negative factor, the incidence of costly and potentially fatal GI bleeds is clearly less with COX-2 inhibitors than with traditional NSAIDs. Ongoing analysis of cost avoidance of GI bleeds will further define the populations that will find COX-2 inhibitors the most beneficial.

Celecoxib (Celebrex)

Inhibits primarily COX-2. COX-2 is considered an inducible isoenzyme, induced during pain and inflammatory stimuli. Inhibition of COX-1 may contribute to NSAID GI toxicity. At therapeutic concentrations, COX-1 isoenzyme is not inhibited and thus, GI toxicity may be decreased. Seek lowest dose of celecoxib for each patient.


Tricyclic antidepressants

Class Summary

A complex group of drugs that have central and peripheral anticholinergic effects, as well as sedative effects. Tricyclic antidepressants have central effects on pain transmission, blocking the active reuptake of norepinephrine and serotonin.

Amitriptyline (Elavil)

Analgesic for certain chronic and neuropathic pain. Inhibits membrane pump responsible for uptake of norepinephrine and serotonin in adrenergic and serotonergic neuron.

Nortriptyline (Pamelor)

Has demonstrated effectiveness in the treatment of chronic pain. By inhibiting the reuptake of serotonin and/or norepinephrine by the presynaptic neuronal membrane, this drug increases the synaptic concentration of these neurotransmitters in the central nervous system.

Pharmacodynamic effects, such as the desensitization of adenyl cyclase and down-regulation of beta-adrenergic receptors and serotonin receptors, also appear to play a role in its mechanisms of action.

Doxepin (Sinequan)

Inhibits histamine and acetylcholine activity and has proven useful in treatment of various forms of depression associated with chronic and neuropathic pain.

Desipramine (Norpramin)

May increase synaptic concentration of norepinephrine in CNS by inhibiting reuptake by presynaptic neuronal membrane. May have effects in the desensitization of adenyl cyclase, down-regulation of beta-adrenergic receptors, and down-regulation of serotonin receptors.



Class Summary

Used to manage pain and provide sedation in neuropathic pain.

Gabapentin (Neurontin)

Membrane stabilizer, a structural analogue of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), which paradoxically is thought not to exert effect on GABA receptors. Appears to exert action via the alpha(2)delta1 and alpha(2)delta2 subunit of the calcium channel.



Class Summary

Pain control is essential to quality patient care. Analgesics ensure patient comfort and have sedating properties, which are beneficial to patients who experience pain.

Acetaminophen (Tylenol)

DOC for pain in patients with documented hypersensitivity to aspirin or NSAIDs, with upper GI disease, or who are taking oral anticoagulants.