Gabapentin for Pain: Balancing Benefit and Harm

Clinical Question

Is gabapentin (Neurontin) effective for the treatment of acute and chronic pain?

Evidence-Based Answer

At high dosages, gabapentin is moderately effective for neuropathic pain, although adverse effects are experienced as often as benefit.

Practice Pointers

Gabapentin is widely used for the treatment of pain, particularly in patients with chronic neuropathic pain. Wiffen and colleagues performed a systematic review of randomized trials assessing the use of gabapentin in acute, chronic, or cancer pain, and found 15 studies with a total of 1,468 patients. Only one study involved patients with acute pain. The remainder enrolled patients with postherpetic neuralgia (two studies), diabetic neuropathy (seven studies), or cancer-related pain, phantom limb pain, Guillain-Barré syndrome, spinal cord injury, and various neuropathic pains (one study each).

Gabapentin was found ineffective for acute pain. The studies of neuropathic pain used a wide variety of dosages, typically 900 to 2,400 mg per day, and in one case up to 3,600 mg per day (the maximum recommended dosage according to the package labeling is 1,800 mg per day).

Data could be combined for six studies of neuropathic pain. In these trials, 42 percent of patients improved with gabapentin versus 19 percent with placebo, giving a combined number needed to treat (NNT) of 4 (i.e., four patients must be treated for one patient to experience an improvement in pain). However, adverse effects were common at the high dosages used in these studies, with 24 percent of patients experiencing dizziness, 20 percent somnolence, 10 percent headache, 10 percent diarrhea, and 7 percent confusion. The overall number needed to harm for adverse effects was also 4. Thus, for every patient who experiences a reduction in pain, another experiences an adverse effect.

The modest benefit of gabapentin for neuropathic pain must be balanced against its adverse effects. Whether this trade-off is worthwhile should be decided by the individual patient. The authors of this review report that based on preliminary data tricyclic antidepressants (NNT = 2) and carbamazepine (Tegretol; NNT = 1.7) are at least as effective as gabapentin and are less expensive (although generic gabapentin costs about one half as much as Neurontin). It is important that physicians carefully assess the balance between benefit and harm for their patients after a therapeutic trial rather than continuing a course of medication indefinitely.

Adalimumab for Rheumatoid Arthritis?

Management of rheumatoid arthritis has shifted toward initiation of DMARDs within three months of diagnosis.1 Adalimumab is a new anti–tumor necrosis factor (TNF) medication that is similar to etanercept (Enbrel) and infliximab (Remicade). It is approved for reducing symptoms and inhibiting structural-damage progression of rheumatoid arthritis in adults with moderately or severely active rheumatoid arthritis who have had an inadequate response to one or more other DMARDs. Adalimumab can be used alone or in combination with methotrexate or other DMARDs.

To assess the safety and effectiveness of adalimumab, Navarro-Sarabia and colleagues conducted a review of controlled trials of adalimumab compared with placebo as monotherapy or in combination with other drugs. Six trials were included, with a total of 2,381 patients. Improvements were assessed using the American College of Rheumatology (ACR) scores ACR 20, ACR 50, and ACR 70 (representing the percentage improvement in tender and swollen joints, pain, health assessment results, and active phase reactants).2 Results were given in terms of the number of patients needed to receive treatment (NNT) for one patient to have a response.

At 24 weeks, the NNT with adalimumab (40 mg subcutaneously every two weeks) plus methotrexate for one patient to have an ACR 20 improvement ranged from 2 to 5. The NNT for an ACR 50 response ranged from 2 to 6, and the NNT for an ACR 70 improvement ranged from 5 to 13. After 52 weeks, the results were similar. Adalimumab monotherapy also was effective, but the size of the effect was lower. The number of patients needed to be treated to harm one patient with serious infection was 30.

The British Society of Rheumatology guidelines3 state that patients with rheumatoid arthritis are candidates for anti-TNF therapy if they have active, ongoing disease that has failed to respond to two of the following standard DMARD regimens: methotrexate and intramuscular gold, hydroxychloroquine (Plaquenil), sulfasalazine (Azulfidine), penicillamine (Cuprimine), azathioprine (Imuran), or leflunomide (Arava). No anti-TNF therapy has been shown to be more effective than any other. Adverse effects of anti-TNF therapy include serious infection and reactivation of latent tuberculosis. Anti-TNF medications may increase the risk of malignancy, systemic lupus erythematosus, cardiovascular disease, demyelinating or neurologic disease, and hematologic complications.

Management of rheumatoid arthritis is an area of rapidly developing research and changing treatment recommendations, and management decisions generally should be made with a consultant who is following these changes closely.