What are the recommended medications for managing phantom pain?

Pharmacological Management of Phantom Pain

First-line medications for phantom pain should include anticonvulsants (gabapentin or pregabalin), tricyclic antidepressants (nortriptyline or desipramine), or serotonin-norepinephrine reuptake inhibitors (duloxetine or venlafaxine). 1

First-Line Medications

Anticonvulsants

• Gabapentin is effective for phantom limb pain, with demonstrated superiority to placebo in clinical trials 1, 2
  • Start at 100-300 mg daily and gradually increase to 900-3600 mg/day in divided doses 1
  • Well-tolerated with few adverse effects; common side effects include dizziness and somnolence which are often transient 3
• Pregabalin is FDA-approved for neuropathic pain conditions with a similar mechanism to phantom pain 1
  • Start at 25-50 mg/day in older adults and gradually increase to 150-600 mg/day in divided doses 1
  • Both gabapentin and pregabalin bind to the α2-δ subunit of voltage-gated calcium channels and inhibit the release of glutamate, norepinephrine, and substance P 4

Antidepressants

• Secondary amine tricyclic antidepressants (TCAs) are preferred over tertiary amines due to fewer anticholinergic side effects 1, 4
  • Nortriptyline: start at 10-25 mg at bedtime and increase every 3-7 days to a final dose of 25-100 mg at bedtime as tolerated 4
  • TCAs exert their action by inhibiting pre-synaptic reuptake of serotonin and norepinephrine, as well as by blocking cholinergic, histaminergic, and sodium channels 4
  • Common side effects include dry mouth, constipation, and sedation 4
• Serotonin-norepinephrine reuptake inhibitors (SNRIs) are also effective first-line options 1, 4
  • Duloxetine: 60 mg once daily 1
  • Venlafaxine: 150-225 mg/day 1

Topical Agents

• Topical lidocaine 5% patches can be applied to painful areas for up to 12 hours daily with minimal systemic absorption 1
• Capsaicin is available in various concentrations but may cause an initial burning sensation 1

Second-Line Medications

Opioid Analgesics

• Opioid analgesics should not be prescribed as first-line agents for long-term management of phantom pain 4
• Consider a time-limited trial of opioid analgesics for patients who do not respond to first-line therapies and report moderate to severe pain 4
• When appropriate, a combination regimen of morphine and gabapentin should be considered for their possible additive effects 4

Tramadol

• Tramadol is a weak μ-opioid agonist with norepinephrine and serotonin reuptake inhibition properties 4
• Can be used at 50 mg once or twice daily with gradual increase to a maximum dose of 400 mg daily 4
• May be justified for immediate and short-term relief 4

Third-Line Medications

Carbamazepine

• Carbamazepine is a sodium channel-blocker commonly used for neuropathic pain 4
• Start at 200 mg at night and gradually increase by 200 mg every 7 days to a final dose of 400-1200 mg, divided in 2-3 doses per day 4
• Once response is achieved, the dose can be tapered to a minimal effective dose 4

Low-Dose Naltrexone (LDN)

• LDN is an opioid antagonist that has shown promise in treating neuropathic pain 4
• Start at 1.5 mg at bedtime with gradual bi-weekly increase of 1.5 mg to a final maximum dose of 4.5 mg taken at bedtime 4
• Common side effects include headache, tachycardia, and vivid dreams 4

Mexiletine

• Mexiletine is a sodium channel blocker structurally related to lidocaine 4
• Can be used at doses of 225-675 mg/day 4
• Due to its poor side effect profile (nausea, headache, sleep disturbances), only recommended for phantom pain refractory to other treatments 4

Treatment Algorithm

1. Initial Assessment:

   • Evaluate pain characteristics, intensity, and functional impact 1
   • Identify comorbidities that might affect treatment selection 4

2. First-Line Treatment:

   • Start with either gabapentin/pregabalin OR a TCA (nortriptyline/desipramine) OR an SNRI (duloxetine/venlafaxine) 1, 4
   • For localized phantom pain, consider adding topical lidocaine 1

3. Reassessment:

   • If substantial pain relief (average pain reduced to ≤3/10) and tolerable side effects, continue treatment 4
   • If partial pain relief (average pain remains ≥4/10) after an adequate trial, add one of the other first-line medications 4
   • If no or inadequate pain relief (<30% reduction) after an adequate trial, switch to an alternative first-line medication 4

4. Second-Line Treatment:

   • If first-line medications fail, consider tramadol or time-limited trial of opioid analgesics 4

5. Third-Line Treatment:

   • Consider carbamazepine, low-dose naltrexone, or mexiletine 4
   • Consider referral to a pain specialist or multidisciplinary pain center 4

Common Pitfalls to Avoid

• Inadequate dosing can lead to treatment failures; ensure proper titration to therapeutic levels before concluding ineffectiveness 1
• Premature discontinuation before reaching therapeutic levels or before allowing adequate time for effect (e.g., TCAs may take 6-8 weeks for full effect) 1
• Overlooking non-pharmacological approaches such as transcutaneous electrical nerve stimulation (TENS) or interventional procedures for refractory pain 1, 5
• Excessive reliance on opioids, which carry significant risks of dependency and adverse effects 1, 4
• Failing to address psychological aspects of phantom pain, which can significantly impact pain perception and treatment outcomes 5, 6