Pharmacy & Therapeutics - March 2008 - (Page 169) CONTINUING EDUCATION CREDIT 600 mg/day divided into two to three doses.28 As one of the few medications approved by the FDA for the treatment of DPN, pregabalin has been studied in several clinical trials (Table 5).29–32 The doses of pregabalin studied ranged from 75 mg up to 600 mg/day. In all of the studies, doses of 300 mg to 600 mg/day were required to produce significant improvements in mean pain scores. Common adverse events noted in clinical trials included dizziness, somnolence, headache, peripheral edema, and weight gain. In each trial reviewed, the investigators concluded that pregabalin was safe and effective for patients with DPN. Oxcarbazepine Oxcarbazepine has been studied in doses ranging from 1,200 to 1,800 mg/day with conflicting results (Table 6).33–35 Although one study showed that oxcarbazepine at doses of 300 to 1,800 mg/day produced significant improvements in Visual Analogue Scale (VAS) pain scores, two other trials examining doses from 600 to 1,800 mg/day showed no benefit. Because a trend toward significance was found in at least one trial, the investigators concluded that additional studies should be conducted to fully elucidate the role of oxcarbazepine in treating DPN. Lamotrigine Oxcarbazepine (Trileptal, Novartis) acts by blocking voltage-sensitive sodium channels and by altering potassium conductance and modulating calcium channel activity. It is best known as an anticonvulsant, but it has also been used to treat bipolar disorder as well as painful conditions such as DPN. Common adverse effects include dizziness, somnolence, headache, ataxia, fatigue, vertigo, vomiting, nausea, abdominal pain, abnormal gait, tremor, diplopia, nystagmus, and abnormal vision.21 The anticonvulsant agent lamotrigine (Lamictal, GlaxoSmithKline) is often used to treat seizure disorders and bipolar disorder. It inhibits the release of glutamate and stabilizes neuronal membranes by inhibiting voltage-sensitive sodium channels. The most common side effects associated with lamotrigine therapy include headache, dizziness, ataxia, somnolence, nausea, diplopia, blurred vision, and rhinitis.21 Lamotrigine has been studied in patients with DPN with mixed results. It has been compared with placebo as well as with amitriptyline (Table 7).36–38 In one study, lamotrigine 200, Table 4 Clinical Trials of Gabapentin Reference Gorson24 Backonja25 Morello26 Dallocchio27 No. Design Treatment GBP 300 mg/day (up to 900 mg/day) or PBO Study Conclusions Significantly more adverse effects with GBP; minimal effect on DPN pain 40 R, DB, PC, CO 165 R, DB, PC 25 R, DB, DD, CO 25 R, OL GBP 900 mg/day (up to 3,600 mg/day) GBP 900–3,600 mg/day produced significantly or PBO lower pain scores compared to PBO GBP 900–1,800 mg/day or AMI 25–75 mg/day GBP 1,200–2,400 mg/day or AMI 30–90 mg/day Both GBP and AMI provided significant pain relief; cost of GBP may preclude its use GBP improved pain and paresthesia intensity scores significantly, compared with AMI; adverse events were significantly higher in AMI group AMI = amitriptyline; CO = crossover; DB = double-blind; DD = double-dummy; GBP = gabapentin; OL = open-label; PBO = placebo; PC = placebo-controlled; R = randomized. Table 5 Clinical Trials of Pregabalin Reference Lesser29 No. Design Treatment PGB 75 mg/day, PGB 300 mg/day, PGB 600 mg/day, or PBO PGB 300 mg/day or PBO PGB 150 mg/day, PGB 600 mg/day, or PBO PBO or flexible-dose schedule 150 mg/day (up to 600 mg/day) or a fixed dose of 300 mg/day (up to 600 mg/day) Study Conclusions PGB 300–600 mg daily produced significant improvements in mean pain scores compared with PBO PGB 300 mg/day produced significant reductions in pain scores compared with PBO PGB 600 mg/day produced significant improvement in mean pain scores compared with PBO Both the flexible-dose and fixed-dose schedules produced significant improvements in pain scores compared with PBO 338 DB, PC Rosenstock30 Richter31 Freynhagen32 146 DB, R, PC, PG 246 DB, R 338 R, DB, PC, PG DB = double-blind; PBO = placebo PC = placebo-controlled; PG = parallel-group; PGB = pregabalin; R = randomized. Vol. 33 No. 3 • March 2008 • P&T® 169
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