Anticonvulsants for Analgesia

In last month’s Pain Perspectives, the “art” of using antidepressants for analgesia in chronic pain was discussed. This month, we will consider what is probably an underutilized class of medications — anticonvulsants – in treating many types of chronic pain syndromes.

As early as the 1950s, reports on the use of medications with anticonvulsant properties for relief of pain began to appear in the literature(1). These medications, however, were more accurately classified as sedatives or tranquilizers, and had little in common with the anticonvulsants that are used today. Early “anticonvulsants” were barbiturates, until the discovery of phenytoin’s properties as a seizure-blocking agent in the 1930s (2). In the 1960s, investigators began to look at carbamazepine as an analgesic agent, particularly in the treatment of facial (3) and headache (4) pain.

The 1970s witnessed the emergence of valproate sodium as an anticonvulsant of interest, with early research indicating some efficacy in its treatment of post-herpetic pain (5). In the late 80s and early 90s, investigators found efficacy for valproate for headache prophylaxis (6), yet results of studies of its utility as a therapeutic agent for other types of pain have not been particularly encouraging (7-9). In comparison to valproate, equivalent efficacy and safety of a new anticonvulsant, topiramate, has been established (10). While widely used in psychiatry for mood stabilization, lamotrigine has been less commonly used for pain management, with a recent Cochrane Review (11) indicating a relative lack of efficacy for the drug as compared to antidepressants and certain other anticonvulsants.

Without a doubt, the anticonvulsants with the strongest evidence-basis for analgesia are gabapentin and pregabalin. Gabapentin has been available since the 1980s, with its efficacies established for treating numerous pain conditions commonly addressed in primary care practice. These conditions include postherpetic neuralgia (12), painful diabetic neuropathy (13), neuropathic pain syndromes considered widely (14), trigeminal neuralgia (15), CRPS (16), and fibromyalgia (17). As an adjunctive agent, the exciting news is that in animal models, gabapentin appears to mitigate opioid-induced hyperalgesia (18). Side effects of gabapentin, however, can be complicated to manage, and may include dizziness, somnolence, peripheral edema, and ataxia/gait disturbance (19).

Most physicians, unfortunately, misunderstand dosing gabapentin. The approach of “start low and go slow” is a prudent one, in that it allows patients to acclimate to some degree to the medication’s side effects. However, for neuropathic pain, the therapeutic goal range for most patients has been established to be in the 1800-3600 mg/day range (20). Far too often in my clinical practice I witness physicians initiating gabapentin therapy at 300 mg/day….and then failing to increase the dosage toward the therapeutic range. A 2013 retrospective study of postherpetic neuralgia patients treated with gabapentin, for example, found a mean daily dosage of only 826 mg (21). Patients may also complain about the necessity of three times daily dosing of gabapentin, although a relatively newly-released once daily form of the drug is now available, and enhanced bioavailability allows for lower dosing to achieve therapeutic effects (22).

Pregabalin has demonstrated empirical support for the treatment of postherpetic neuralgia (23), painful diabetic neuropathy (24), central neuropathic pain (25), fibromyalgia (26), and trigeminal neuralgia (27). Side effects are similar to those of gabapentin, including dizziness, somnolence, and peripheral edema (28). When directly compared to gabapentin, safety and efficacy were similar for both drugs in the treatment of painful diabetic neuropathy (29). Issues of appropriate dosing and pharmacogenomics need to be taken into consideration when comparing relative efficacies. And, of course, should it become necessary to discontinue an anticonvulsant, it should be done slowly — as abrupt cessation can result in seizures (30).

For additional hands-on training on using anticonvulsants to treat chronic pain, readers are encouraged to attend PAINWEEK — as this is a topic regularly covered by thought leaders in the field. Until next month, let’s continue to expand our primary care pain management armamentaria!

REFERENCES

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