Pharmacologic management of neuropathic pain

Medications for Neuropathic Pain It is essential when taking a patient’s history to listen for descriptions such as burning, shooting, pins and needles, or electricity, and for pain associated with numbness. Such a history suggests neuropathic pain, which is treated with some medications not typically used for other types of pain. While opioids are effective for neuropathic pain, a number of nonopioid medications also have been found to be effective in randomized trials (Table 1).



Successful management of neuropathic pain often requires the use of more than one effective medication. The tricyclic antidepressants (TCAs) are good first-line therapy. Nortriptyline and desipramine are preferred because they cause less orthostatic hypotension and have fewer anticholinergic effects than amitriptyline. Start with a low dosage (10–25 mg orally daily) and titrate upward in 10 mg increments every 4 or 5 days to 50 mg. It may take several weeks for a TCA to have its full effect as a neuropathic pain analgesic.


The calcium channel alpha2-delta ligands gabapentin and pregabalin are also first-line therapies for neuropathic pain. Both medications can cause sedation, dizziness, ataxia, and gastrointestinal side effects but have no significant drug interactions. Both drugs require dose adjustments in patients with kidney dysfunction. Gabapentin should be started at low dosages of 100–300 mg orally three times a day and titrated upward by 300 mg/d every 4 or 5 days with a typical effective dose of 1800–3600 mg/d.

Pregabalin should be started at 150 mg/d in two or three divided doses. If necessary, the dose of pregabalin can be titrated upward to 300–600 mg/d in two or three divided doses. Both drugs are relatively safe in accidental overdose and may be preferred over TCAs for a patient with a history of heart failure or arrhythmia or if there is a risk of suicide. Prescribing both gabapentin and morphine for neuropathic pain may provide better analgesia at lower doses than if each is used as a single agent.

The selective serotonin norepinephrine reuptake inhibitors (SSNRIs), duloxetine and venlafaxine, are also first-line treatments for neuropathic pain. Patients should be advised to take duloxetine on a full stomach because nausea is a common side effect. Duloxetine generally should not be combined with other serotonin or norepinephrine uptake inhibitors, but it can be combined with gabapentin or pregabalin. Because venlafaxine can cause hypertension and induce ECG changes, patients with cardiovascular risk factors should be carefully monitored when starting this drug. Other medications effective for neuropathic pain include tramadol and the 5% lidocaine patch.


The 5% lidocaine patch is effective in postherpetic neuralgia and may be effective in other types of localized neuropathic pain.

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