What's the best next step for a patient with chronic nerve pain, who's tried duloxetine, amitriptyline, and nortriptyline, and now requests gabapentin or Lyrica (pregabalin), given a history of liver damage?

From the Guidelines

For a patient with chronic nerve pain who has tried duloxetine, amitriptyline, and nortriptyline without success and now requests gabapentin or pregabalin (Lyrica), but has a history of liver damage, pregabalin would be the preferred option. Pregabalin is primarily excreted unchanged through the kidneys (90%) with minimal liver metabolism, making it safer for patients with hepatic impairment 1. Start with a low dose of 50-75 mg twice daily and gradually titrate up to an effective dose, typically 150-300 mg twice daily, based on pain relief and tolerability. Monitor for side effects such as dizziness, somnolence, peripheral edema, and weight gain. Kidney function should be assessed before starting treatment and periodically thereafter, as dose adjustments are necessary for renal impairment. Gabapentin, while also primarily renally excreted, undergoes some hepatic metabolism and may have unpredictable pharmacokinetics in liver disease 1. Both medications require gradual discontinuation to avoid withdrawal symptoms. If pregabalin is ineffective or poorly tolerated, other non-pharmacological approaches like physical therapy, cognitive behavioral therapy, or interventional pain procedures might be considered as alternatives.

Given the patient's history of liver damage, it is crucial to prioritize medications with minimal liver metabolism, and pregabalin fits this criterion better than gabapentin 1. The patient's request for gabapentin or pregabalin after failing first-line treatments aligns with the NeuPSIG guidelines, which recommend considering these medications as part of the treatment algorithm for neuropathic pain 1.

Key considerations in managing this patient's chronic nerve pain include:

• Monitoring liver function through a liver panel, as ordered
• Assessing kidney function before starting pregabalin and adjusting the dose as necessary
• Gradually titrating the dose of pregabalin to achieve optimal pain relief while minimizing side effects
• Considering non-pharmacological approaches if pregabalin is ineffective or not tolerated
• Prioritizing the patient's safety and quality of life in the treatment plan, given the history of liver damage and previous treatment failures 1.

From the FDA Drug Label

Pregabalin is a prescription medicine used in adults, 18 years of age and older to treat: pain from damaged nerves (neuropathic pain) that happens with diabetes pain from damaged nerves (neuropathic pain) that follows healing of shingles fibromyalgia (pain all over your body) pain from damaged nerves (neuropathic pain) that follows spinal cord injury Gabapentin tablets are indicated for the management of postherpetic neuralgia in adults, and as an adjunctive therapy in the treatment of partial onset seizures in patients 3 years of age and older.

The best next step for a patient with chronic nerve pain who has tried duloxetine, amitriptyline, and nortriptyline, and now requests gabapentin or Lyrica (pregabalin) is to:

• Consider the patient's history of liver damage and assess the potential risks and benefits of each medication.
• Evaluate the patient's kidney function, as both gabapentin and pregabalin require dose adjustments in patients with renal impairment.
• Choose the medication that is most appropriate for the patient's specific condition and medical history.
• Monitor the patient closely for potential side effects and adjust the dose or discontinue the medication as needed.
• Consider alternative treatments, such as physical therapy, which the patient is already scheduled to receive. 2 3

From the Research

Patient Background

• The patient is a 39-year-old male with chronic nerve pain in his left hand.
• He has tried duloxetine, amitriptyline, and nortriptyline before with no improvement.
• The patient is now requesting gabapentin or Lyrica (pregabalin) for his nerve pain.
• He has a history of liver damage and declines to take NSAIDs.
• A liver panel has been ordered for this visit.

Treatment Options

• Gabapentin and pregabalin are commonly used to treat neuropathic pain, but their efficacy in combination with other medications is still being studied 4, 5.
• Duloxetine and amitriptyline have been shown to reduce neuropathic pain by inhibiting primary sensory input to spinal dorsal horn neurons via α1- and α2-adrenergic receptors 6.
• A study comparing amitriptyline supplemented with pregabalin, pregabalin supplemented with amitriptyline, and duloxetine supplemented with pregabalin found that all three treatment pathways had similar analgesic efficacy 4.
• Another study found that the combination of pregabalin with duloxetine or amitriptyline improved the bioavailability of pregabalin and potentiated the efficacy of the antiallodynic effect of pregabalin alone 5.

Next Steps

• Considering the patient's history of liver damage, it is essential to monitor his liver function while prescribing any new medications.
• Physical therapy (PT) has been prescribed for the patient, which may help alleviate his nerve pain.
• The patient's request for gabapentin or Lyrica (pregabalin) should be considered, given the evidence supporting their use in treating neuropathic pain 4, 5, 7.
• However, the patient's previous lack of response to duloxetine and amitriptyline should be taken into account when deciding on the next course of treatment 8, 6.