As a rule, treatment of neuropathic pain is more difficult than is treatment of nociceptive pain. Referral to a specialist should be considered if the basic measures outlined below are not successful. Physicians should also be reminded that some neuropathic pain (especially when mixed with nociceptive pain) may respond to the agents discussed above, NSAIDs and opioids. However, these agents are less effective for pure neuropathic pain than they are for nociceptive pain.
Three major classes of medication are commonly used in the treatment of neuropathic pain: antidepressants, especially tricyclics; anticonvulsants, especially gabapentin and carbamazepine; and sodium channel blockers, especially mexiletine. A primary care provider may initiate tricyclics, carbamazepine, or gabapentin. Most primary care providers should seek consultation before using other anticonvulsants or sodium channel blocking agents. As a special case, neuropathic pain caused by tumor-related nerve compression is often relieved by steroids by alleviating swelling around the tumor, thereby reducing compression and pain. Dexamethasone 4-8 mg qd. is often effective.
The analgesic properties of these agents appear to relate primarily to their ability to block neuronal reuptake of serotonin and norepinephrine in the CNS. The anticholinergic properties of tricyclics do not appear to have analgesic effects. It is therefore curious that the most anticholinergic agent of available tricyclics, amitriptyline, is used most frequently by physicians for neuropathic pain. This is probably because it is the oldest agent. Agents with less anticholinergic effects, such as nortriptyline and desipramine, should be considered. (Note: these agents may still cause hypotension and should not be used in patients with heart block.) Tricyclics have been used particularly for dysesthetic and constant neuropathic pain, such as diabetic neuropathy. However, they can be used successfully for more paroxysmal pain, such as trigeminal neuralgia. There appears to be a dose-response curve in the use of these agents. While therapy should generally be initiated at low doses (10-25 mg for most tricyclics), dosage should be slowly raised to therapeutic levels (usually 75 mg) or until unacceptable side effects appear if pain relief is inadequate.9
Newer antidepressants, such as serotonin reuptake inhibitors (fluoxetine, sertraline), have been inconsistent in their analgesic properties and are not recommended for analgesia. The reason for this lack of analgesia is puzzling and not known.
Most anticonvulsants have been found to have some analgesic effect on neuropathic pain.36 The most studied is carbamazepine. It has been most commonly used in paroxysmal pain syndromes, such as trigeminal neuralgia, although efficacy has also been demonstrated in more constant pain syndromes, such as diabetic neuropathy. In choosing between a tricyclic and carbamazepine as a first-line agent, it would be reasonable to consider the "two-for-the-price-of-one" principle. Depressed patients with either steady or paroxysmal pain may do better with a tricyclic (barring contraindications). A patient with seizures may better benefit from carbamazepine.
Carbamazepine can be sedating. Patients treated with it should have complete blood counts (CBC) and liver function tests monitored, as blood dyscrasias and LFT abnormalities can occur. These generally resolve with discontinuation of the drug. In patients prone to blood dyscrasias or liver abnormalities, carbamazepine should be used with caution, if at all.
A new anticonvulsant, gabapentin, is increasingly used in the treatment of neuropathic pain.37-39 It is remarkably well tolerated, with some evidence of anxiolytic effects, and therefore may be helpful for anxious patients.40,41 Unlike carbamazepine, it lacks significant drug-drug interactions. Patients may experience nausea, especially with rapid dose escalation, or dizziness with higher doses. I have noticed a tendency recently for physicians to prescribe gabapentin in very low doses, 100 mg qhs, for example. Gabapentin is an expensive drug. It makes no sense to prescribe this drug in dosages that virtually prohibit any efficacy. When used, the dosage should be titrated up to therapeutic levels and the patient observed for a clinical response. If unresponsive, the medication should be discontinued.
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Palliative Care Perspectives
James L. Hallenbeck, M.D.
Copyright © 2003 by Oxford University Press, Inc.
The online version of this book is used with permission of the publisher and author on web sites affiliated with the Inter-Institutional Collaborating Network on End-of-life Care (IICN), sponsored by Growth House, Inc.