Treatment of Neuropathic Pain

Kristen Jefferies, Pharm.D.

Disclosures

Semin Neurol. 2010;30(4):425-432. 

In This Article

Opioid Analgesics

Randomized controlled trials have shown beneficial effects of opioids (including oxycodone, methadone, morphine, and levorphanol) for the treatment of DPN, PHN, painful polyneuropathy, and phantom limb pain.[6] Comparative trials have shown similar benefit with opioids when compared with TCAs and gabapentin, but more frequent side effects occurred with opioids.[6] NeuPSIG recommends opioids as second-line medications when an adequate response is not achieved with first-line medications or as a first-line option when immediate pain relief is necessary and short-term for acute neuropathic pain.[5] The EFNS recommends opioid medications as second- or third-line options for painful diabetic neuropathy, PHN, and central neuropathic pain because of limited trials assessing long-term safety and abuse potential.[2] The Canadian Pain Society recommends opioids (excluding methadone) as third-line agents for the treatment of painful diabetic neuropathy, PHN, and other neuropathic pain conditions. Methadone is considered a fourth-line agent because of limited clinical evidence, difficulty with titration, and regulatory status in Canada.[4]

The appropriate dose is widely variable from patient to patient and depends on prior opioid exposure. The typical initial dose is 10 to 15 mg of morphine or equianalgesic dose every 4 hours or as needed. After 1 to 2 weeks the total daily dose can be converted to an equianalgesic dose of a longer acting opioid medication such as transdermal fentanyl, extended release oxycodone, or extended release morphine. A scheduled long-acting opioid is typically preferred. If pain is not improved after an adequate trial, the medication should be tapered and discontinued.[5]

Compared with other medications, opioids typically have a quick onset of pain relief. Opioid medications are particularly useful for short-term use to treat acute exacerbations or during the titration phase of a first-line medication.[5] There are several disadvantages associated with the use of opioid medications. They are often poorly tolerated. Common side effects include sedation, constipation, and nausea. Constipation typically does not improve over time and a bowel regimen may be required. These medications can increase risk of falls and cognitive problems in elderly patients. Rare but serious side effects include hypogonadism, immunologic changes, and hyperalgesia. Opioids are associated with a risk of misuse or addiction of 5% to 50% in other chronic pain conditions. Risk factors for abuse include a history of or current substance abuse, major psychiatric disorders, and family history of substance abuse.[5]

A Cochrane review of 23 studies assessed the efficacy of opioid medications for the treatment of neuropathic pain.[15] The majority of these studies assessed treatment for less than 24-hour duration, single doses, or intravenous (IV) administration, but nine studies were 8 to 70 days in duration and included 460 patients with various types of neuropathic pain (painful diabetic neuropathy, PHN, and phantom limb pain). The opioid medications studied were morphine (four trials), oxycodone (three trials), methadone (two trials), and levorphanol (one trial). The opioid medications were superior to placebo in all placebo-controlled studies. A meta-analysis of the seven studies with suitable data concluded that overall opioid medications were associated with a reduction in pain intensity of 13 points on a scale of 0 to 100. The most common side effects were nausea, constipation, sedation, and vomiting. The NNH for drug discontinuation was 16.7 (95% CI 9.1–100).

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