What is the comparison between duloxetine (Cymbalta) and gabapentin (Neurontin) for the treatment of neuropathic pain?

From the Guidelines

Duloxetine is the preferred medication for neuropathic pain, particularly in patients with diabetic neuropathy, due to its efficacy in reducing pain and its additional benefits in treating comorbid depression and anxiety, as supported by the most recent and highest quality study 1.

Comparison of Duloxetine and Gabapentin

Both duloxetine and gabapentin are effective medications for neuropathic pain, but they work through different mechanisms and have distinct side effect profiles.

• Duloxetine, typically started at 30mg daily and increased to 60mg daily after one week, is a serotonin-norepinephrine reuptake inhibitor that enhances pain inhibitory pathways.
• Gabapentin, usually initiated at 300mg daily and gradually titrated up to 1800-3600mg daily in divided doses, works by binding to calcium channels to reduce excitatory neurotransmitter release.

Efficacy and Side Effects

• Duloxetine has been shown to be effective in reducing pain in diabetic neuropathy, with a number needed to treat (NNT) of 4.9 for 120 mg/day and 5.2 for 60 mg/day 1.
• Gabapentin has also been shown to be effective in reducing pain in diabetic neuropathy, but its efficacy may be lower than that of duloxetine, with an NNT of 4.04 for 600 mg/day and 5.99 for 300 mg/day 1.
• Common side effects of duloxetine include nausea, dry mouth, constipation, and dizziness, while common side effects of gabapentin include sedation, dizziness, and peripheral edema.

Patient Selection

• Duloxetine may be preferred in patients with concurrent depression or when once-daily dosing is important for adherence.
• Gabapentin might be better for elderly patients or those with renal impairment (with dose adjustment).

Treatment Approach

• Both medications require gradual titration to minimize side effects and should be tapered slowly when discontinuing to avoid withdrawal symptoms.
• Treatment response should be assessed after 4-6 weeks at therapeutic doses.
• The most recent and highest quality study 1 supports the use of duloxetine as a first-line treatment for neuropathic pain, particularly in patients with diabetic neuropathy.

From the Research

Comparison of Duloxetine and Gabapentin for Neuropathic Pain

• Duloxetine is a balanced serotonin and noradrenaline reuptake inhibitor licensed for the treatment of major depressive disorders, urinary stress incontinence, and the management of neuropathic pain associated with diabetic peripheral neuropathy 2, 3, 4.
• Gabapentin is an anticonvulsant that is also used to treat neuropathic pain, and is often recommended as a first-line treatment 5, 6.
• Studies have shown that duloxetine is effective in treating painful diabetic peripheral neuropathy, with a risk ratio for ≥ 50% pain reduction at 12 weeks of 1.73 (95% CI 1.44 to 2.08) 2.
• Gabapentin has also been shown to be effective in treating neuropathic pain, although the exact mechanism of action is not fully understood 5, 6.
• A comparison of the two medications found that duloxetine and gabapentin are both effective in treating neuropathic pain, but that duloxetine may be more effective in treating painful diabetic peripheral neuropathy 2, 4.
• However, gabapentin is often recommended as a first-line treatment due to its favorable side effect profile and lower risk of adverse events 5, 6.

Efficacy and Safety

• Duloxetine has been shown to be effective in treating neuropathic pain, with a number needed to treat (NNT) of 5 (95% CI 4 to 7) for painful diabetic peripheral neuropathy 2.
• Gabapentin has also been shown to be effective, although the exact NNT is not well established 5, 6.
• Both medications have been associated with adverse events, although duloxetine may have a higher risk of adverse events, particularly at higher doses 2, 3, 4.
• Gabapentin is generally well-tolerated, although it can cause dizziness, drowsiness, and other side effects 5, 6.

Clinical Guidelines

• The most recent clinical guidelines recommend duloxetine, gabapentin, and pregabalin as first-line treatments for neuropathic pain 5, 6.
• Tricyclic antidepressants and opioids are also recommended, although they are generally considered second-line treatments due to their higher risk of adverse events 5, 6.
• The guidelines emphasize the importance of individualizing treatment and considering the specific needs and circumstances of each patient 5, 6.