Guidelines for the use of orally and parenterally administered opioids for general and cancer-related pain are contained in numerous publications, most of which converge on similarly structured plans. The document issued by the U.S. Department of Health and Human Services in 1994 had great influence and still can be used as a basic resource for cancer pain treatment (the primary source and a special report referring to it by Jacox and colleagues are given in the references).
Supplemental Medications for the
Treatment of Pain
Tricyclic antidepressants, especially the methylated forms (imipramine, amitriptyline, and doxepin), block serotonin reuptake and thus enhance the action of this neurotransmitter at synapses and putatively facilitate the action of the intrinsic opiate analgesic system. As a general rule, relief is afforded with tricyclic antidepressants in the equivalent dose range of 75 to 125 mg daily of amitriptyline, but little benefit accrues with higher amounts. The specific serotonin reuptake inhibitors (SSRI) antidepressants seem not to be as effective for the treatment of chronic neuropathic pain (see review by McQuay and colleagues) but these agents have not yet been extensively investigated in this clinical condition.
Certain antiepileptic drugs (AEDs) have a beneficial effect on many central and peripheral neuropathic pain syndromes but are generally less effective for causalgic pain caused by partial injury of a peripheral nerve. The mode of action of phenytoin, carbamazepine, gabapentin, levetiracetam, and other AEDs in suppressing the lancinating pains of tic douloureux and certain polyneuropathies, as well as pain after spinal cord injury and myelitis, is not fully understood, but they are widely used. Their action has been attributed to the blocking of sodium channels on axons, thereby reducing the evoked and spontaneous activity in nerve fibers. The full explanation is certainly more complex and related to separate central and peripheral sites, as summarized by Jensen. Often, large doses must be utilized—for example, more than 2,400 mg per day for gabapentin for full effect—but the soporific and ataxic effects of these medications may be poorly tolerated.
Most often a combination of medications is used for the treatment of intractable chronic pain. A common combination is the addition of gabapentin to an opioid such as morphine; perhaps not surprisingly, this was superior to either drug alone in a crossover trial in patients with postherpetic neuralgia and diabetic neuropathy conducted by Gilron and colleagues.
Table 7-3 summarizes the main analgesics (nonnarcotic and narcotic), antiepileptics, and antidepressant drugs in the management of chronic pain.
Treatment of Neuropathic Pain