How to manage foot pain and maintain function in a patient with Charcot-Marie-Tooth disease (CMT) and recent initiation of amitriptyline therapy?

From the Guidelines

The patient should continue with amitriptyline 25 mg QPM for at least 4 weeks to evaluate its effectiveness for neuropathic pain management, focusing on conservative management through physical therapy to maintain function and address foot deformities associated with Charcot-Marie-Tooth disease (CMT). The patient's current footwear seems adequate since he does not experience discomfort, but consideration for specialized orthotic devices or custom-molded shoes may be necessary in the future if symptoms progress, as suggested by studies on foot care for patients with neuropathy and bony deformities 1.

Current Management

• The patient has been started on amitriptyline, which is a reasonable approach for managing neuropathic pain associated with CMT.
• Physical therapy is crucial for maintaining muscle strength, preventing contractures, and improving balance in CMT patients.
• The focus on symptom management and maintaining function is appropriate, given the patient's condition.

Future Considerations

• If the patient's symptoms do not improve after 4 weeks on amitriptyline, dose adjustment or alternative neuropathic pain medications like gabapentin or pregabalin may be considered.
• Regular assessment of the patient's footwear needs is necessary, as patients with bony deformities like hammertoes may require extra wide or deep shoes, or even custom-molded shoes if commercial therapeutic footwear is inadequate 1.
• The patient's foot care should include regular inspections for signs of increased plantar pressure, such as erythema, warmth, or calluses, and appropriate management strategies should be implemented to prevent complications.

From the FDA Drug Label

1. Dosage and Administration Oral Dosage Dosage should be initiated at a low level and increased gradually, noting carefully the clinical response and any evidence of intolerance. The usual maintenance dosage of amitriptyline HCl is 50 to 100 mg per day. In some patients, 40 mg per day is sufficient. A small number of hospitalized patients may need as much as 300 mg a day. Adolescent and Elderly Patients In general, lower dosages are recommended for these patients Ten mg 3 times a day with 20 mg at bedtime may be satisfactory in adolescent and elderly patients who do not tolerate higher dosages.

The patient was started on 25 mg QPM of amitriptyline, which is lower than the recommended initial dosage for adults.

• The recommended initial dosage for adults is 75 mg a day in divided doses.
• The dosage should be increased gradually, noting carefully the clinical response and any evidence of intolerance.
• It is recommended to wait at least 30 days to evaluate the therapeutic effect of amitriptyline, as an adequate therapeutic effect may take as long as 30 days to develop 2.

From the Research

Patient's Condition and Treatment

• The patient is a 26-year-old male with Charcot-Marie-Tooth disease (CMT) and complaints of foot pain, exhibiting hammertoe and an abnormal arch in both feet.
• The patient has been started on amitriptyline 25 mg QPM by the MH team for symptom management and maintaining function, with a focus on physical therapy.
• The patient is advised to wait at least 4 weeks to evaluate the therapy.

Amitriptyline for Neuropathic Pain

• According to 3, amitriptyline is a tricyclic antidepressant widely used to treat chronic neuropathic pain, but there is no first-tier or second-tier evidence for its effectiveness in treating any neuropathic pain condition.
• The study found that only 38% of participants benefited with amitriptyline and 16% with placebo, with most participants not achieving adequate pain relief.
• Another study 4 also found no top-tier evidence for amitriptyline in treating neuropathic pain or fibromyalgia, but second-tier evidence suggested some evidence of effect in painful diabetic neuropathy, mixed neuropathic pain, and fibromyalgia.

Amitriptyline for Musculoskeletal Complaints

• A systematic review 5 found that the role of amitriptyline in musculoskeletal pain is not as clearly defined as in classical neuropathic pain conditions.
• The review included seven studies on amitriptyline in musculoskeletal complaints, with two studies finding positive results, including improved function in arm pain compared to placebo.
• However, the review concluded that more studies are required to establish for whom amitriptyline works better than other analgesics.

Mechanism of Action and Side Effects

• A study 6 found that amitriptyline activated noradrenergic neurons in the locus coeruleus and increased noradrenergic fibers density in spinal nerve ligation rats, suggesting that amitriptyline could still produce analgesia under pathological dysfunction of the descending noradrenergic system.
• Another study 3 found that more participants experienced at least one adverse event with amitriptyline (55%) compared to placebo (36%), with a risk ratio of 1.5 and a number needed to treat for an additional harmful outcome of 5.2.