Treatment of Neuropathic Pain

Kristen Jefferies, Pharm.D.


Semin Neurol. 2010;30(4):425-432. 

In This Article

Tramadol (Ultram®)

Tramadol (Ultram®; Ortho-McNeil-Jansson Pharmaceuticals, Titusville, NJ) is a weak Mu opioid receptor agonist and weakly inhibits serotonin and norepinephrine reuptake. Clinical trials have shown efficacy for tramadol in the treatment of painful diabetic neuropathy, PHN, painful polyneuropathy, and phantom limb pain.[6] The NeuPSIG recommends tramadol as a second-line treatment for neuropathic pain but may be used as first-line treatment in the same clinical situations when opioids could be considered first line.[5] The EFNS recommends tramadol as a second- or third-line treatment option for painful diabetic neuropathy, PHN, and central neuropathic pain and as a first-line option for acute exacerbation of painful diabetic neuropathy.[2] Tramadol is recommended as a third-line agent by the CPS.[4]

Tramadol is typically initiated at a dose of 50 mg one to two times per day and titrated as needed to a maximum total daily dose of 400 mg (100 mg 4 times daily). It is available in immediate release and sustained release formulations and in combination with acetaminophen.

Like the strong opioid analgesics, tramadol is associated with a quick onset of pain relief. It is associated with a lower risk of abuse than strong opioid receptor agonists and is less sedating.[6]

Common side effects of tramadol include sedation, nausea, constipation, orthostatic hypotension, and decreased seizure threshold. Tramadol may be associated with an increased risk of serotonin syndrome when combined with other serotonergic drugs.[5]

A Cochrane review assessed the use of tramadol for neuropathic pain.[16] In five placebo controlled studies of 4 to 7 weeks duration, tramadol was superior to placebo for the treatment off various types of neuropathic pain. A meta-analysis of three of these studies (303 patients) calculated a NNT of 3.8 (95% CI 2.8–6.3) for a 50% reduction in pain. The most common side effects were nausea, vomiting, sweating, dry mouth, dizziness, and sedation. The NNH to cause drug discontinuation was 7.7 (95% CI 4.6–20). In these studies, tramadol was associated with a very low abuse potential.


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