What is the recommended treatment for neuropathy using gabapentin (Neurontin) and Flexeril (cyclobenzaprine)?

Treatment of Neuropathic Pain with Gabapentin and Cyclobenzaprine

Gabapentin is recommended as first-line pharmacological treatment for neuropathic pain, while cyclobenzaprine (Flexeril) is not indicated for neuropathic pain management and should not be combined with gabapentin for this purpose. 1

First-Line Treatment: Gabapentin

Dosing and Titration

• Start gabapentin at 100-300 mg at bedtime or 100-300 mg three times daily 1
• Gradually increase by 100-300 mg every 1-7 days as tolerated 1
• Target dose: 1800-3600 mg/day in divided doses (2-3 times daily) 1
• Typical effective regimen: 2400 mg/day in divided doses 1, 2
• Slower titration recommended for elderly or medically frail patients 1
• Dose adjustment required for patients with renal insufficiency 1

Efficacy

• Gabapentin provides substantial pain relief (≥50% reduction) in approximately 38% of patients with diabetic neuropathy and 32% of patients with postherpetic neuralgia 3
• Number needed to treat (NNT) ranges from 5.9 for diabetic neuropathy to 6.7 for postherpetic neuralgia 3
• Onset of analgesic effect may be seen within days, but an adequate trial requires 2-8 weeks 1, 4

Common Side Effects

• Dizziness (19%)
• Somnolence (14%)
• Peripheral edema (7%)
• Gait disturbance (9%) 3
• Most side effects are mild to moderate and often transient, typically subsiding within approximately 10 days from treatment initiation 2, 5

Role of Cyclobenzaprine (Flexeril)

Cyclobenzaprine is a muscle relaxant that is not indicated for neuropathic pain treatment in any of the clinical guidelines reviewed. None of the major neuropathic pain treatment guidelines mention cyclobenzaprine as a recommended agent for neuropathic pain 1.

Alternative or Add-on Treatments if Gabapentin is Ineffective

Second-Line Options

1. Pregabalin (similar mechanism to gabapentin)

   • Starting dose: 50 mg three times daily or 75 mg twice daily
   • Target dose: 300-600 mg/day in divided doses
   • May provide faster onset of relief than gabapentin 1

2. Tricyclic Antidepressants (e.g., nortriptyline, desipramine)

   • Starting dose: 10-25 mg at bedtime
   • Target dose: 50-150 mg at bedtime
   • Secondary amines (nortriptyline, desipramine) better tolerated than tertiary amines (amitriptyline, imipramine) 1
   • Caution in patients with cardiovascular disease; avoid doses >100 mg/day due to risk of sudden cardiac death 1

3. Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

   • Duloxetine: 30-60 mg daily, up to 120 mg daily
   • Venlafaxine: 37.5-225 mg daily 1

Topical Options

• Lidocaine 5% patch: Apply to painful site daily (up to 3 patches for 12-18 hours) 1
• Capsaicin: For peripheral neuropathic pain; can provide pain relief for up to 12 weeks 1

Treatment Algorithm

1. Initial Treatment:

   • Begin gabapentin at 300 mg at bedtime
   • Increase to 300 mg twice daily on day 2
   • Increase to 300 mg three times daily on day 3
   • Continue titration by 300 mg every 3-7 days until reaching effective dose (typically 1800-2400 mg/day)
   • Evaluate efficacy after 4 weeks at target dose

2. If inadequate response after 8 weeks:

   • Switch to pregabalin OR
   • Add a tricyclic antidepressant (if no contraindications) OR
   • Add an SNRI

3. If still inadequate:

   • Consider topical agents (lidocaine, capsaicin) for localized pain
   • Consider referral to pain specialist for evaluation of combination therapy or interventional approaches

Important Caveats and Pitfalls

• Do not combine gabapentin with cyclobenzaprine for neuropathic pain as there is no evidence supporting this combination and it may increase risk of sedation
• Avoid abrupt discontinuation of gabapentin; taper gradually over at least one week to prevent withdrawal symptoms
• Monitor for increased suicidal thoughts and behavior, especially during initial treatment period
• Adjust doses in renal impairment to prevent toxicity
• Be aware of drug interactions, particularly with opioids and other CNS depressants which may increase sedation
• Reassess regularly for efficacy and side effects; discontinue if no benefit after adequate trial

Gabapentin remains the most evidence-based first-line treatment for neuropathic pain, with well-established efficacy and a favorable safety profile when properly titrated 1, 3.