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Bupropion is an antidepressant with a broad spectrum of activity of neurotransmitters, including NE, 5-HT, and dopamine, and has displayed some prom ise with respect to efficacy in neuropathic pain (Semenchuk et al. 2001) (see Table 5-6). Bupropion lacks significant cardiac or anticholinergic side effects and has fewer risks of drug interactions; however, there is a risk of seizure associated with higher doses.

Mirtazapine may be helpful in mitigating symptoms associated with fibromyalgia (Samborski et al. 2004) and prophylaxis of chronic daily tension headache (Bendtsen and Jensen 2004). Researchers in two studies—one involving patients with neuropathy and the other involving chronic headache patients— found pain-mitigating effects with nefazodone. Patients with migraine or tension headache experienced marked reductions in the frequency, severity, and duration of recurrent headache when treated with daily nefazodone (Goodnick et al. 2000; Saper et al. 2001). Nefazodone use has been linked with hepatic dysfunction, and its use should be avoided in patients concurrently taking medications with potential hepatotoxic effects (e.g., acetaminophen). Additional clinical trials investigating the roles of these antidepressants are warranted.

Trazodone appears to be minimally, but not conclusively, efficacious in pain. Although two double-blind studies demonstrated efficacy of trazodone in diabetic neuropathy and pain resulting from nerve deafferentation (Khurana 1983; Ventafridda et al. 1988), the effects on patients with headache, fibromyalgia, rheumatoid arthritis, or chronic low back pain seemed less promising (Ansari 2000). Trazodone has been employed for its sedative properties. Some patients, particularly those taking opiates or other sedating agents, may find the sedative effects too incapacitating. The analgesic properties of trazodone appear to be independent of its sedative effects (Ansari 2000). Caution concerning other potential adverse effects associated with trazodone use (e.g., orthostasis, priapism) is warranted; doses should be kept to a minimum and increased only gradually to reduce the risk of incurring adverse effects.

The MAOI phenelzine has been found to be effective in the treatment of selected pain disorders. However, MAOI use has been limited by medication side effects, the need for a tyramine-free diet, and the potential risk of drug interactions (e.g., serotonin syndrome arising from coadministration with me-peridine).

Although not currently available in the United States, emerging antidepressant therapies potentially useful for pain include milnacipran, an SNRI; and reboxetine, an NE reuptake inhibitor (Krell et al. 2005; Leo and Brooks 2006; Vitton et al. 2004). Milnacipran has demonstrated efficacy in the relief

Table 5-8. Uses of anticonvulsants in various pain conditions

Carbamazepine

Trigeminal neuralgia Neuropathy Gabapentin Neuropathy Atypical facial pain Reflex sympathetic dystrophy Central pain Migraine prophylaxis Divalproex sodium

Migraine prophylaxis Neuropathy Lamotrigine

Trigeminal neuralgia Peripheral neuropathy Central neuropathy

Oxcarbazepine

Trigeminal neuralgia Tiagabine

Diabetic polyneuropathy Peripheral neuropathy Phantom limb pain Pregabalin

Postherpetic neuralgia Diabetic neuropathy Phenytoin

Trigeminal neuralgia Diabetic neuropathy Topiramate Neuropathy Migraine prophylaxis of pain associated with fibromyalgia; reboxetine has been used in case reports of patients with musculoskeletal pain and fibromyalgia.

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