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Head-to-head comparisons of drugs commonly prescribed for painful diabetic neuropathy are scarce. In this double-blind trial, funded by a maker of pregabalin (an anticonvulsant; Lyrica), 83 patients (mean age, 65) with painful diabetic neuropathy were randomized to receive amitriptyline (a tricyclic antidepressant), duloxetine (a serotonin-norepinephrine reuptake inhibitor; Cymbalta), or pregabalin. Patients were treated for 4 weeks; total daily doses were titrated to a maximum of 75 mg of amitriptyline, 120 mg of duloxetine, and 600 mg of pregabalin.
At 4 weeks, mean pain scores had improved in all three groups, with no significant differences among groups. Duloxetine lessened sleep efficiency compared with the other two drugs, whereas pregabalin was associated with slightly worse cognitive function than the other two drugs. Adverse effects (particularly fatigue, dizziness, and somnolence) were most common with pregabalin. Premature withdrawal from the study due to adverse events occurred in six pregabalin recipients, three duloxetine recipients, and one amitriptyline recipient.
Boyle J et al. Randomized, placebo-controlled comparison of amitriptyline, duloxetine, and pregabalin in patients with chronic diabetic peripheral neuropathic pain: Impact on pain, polysomnographic sleep, daytime functioning, and quality of life. Diabetes Care 2012 Dec; 35:2451. (http://dx.doi.org/10.2337/dc12-0656)
Comment
These three drugs had similar effects on painful diabetic neuropathy. Pregabalin was the least well tolerated, perhaps because of the high dose (note that target doses for duloxetine and pregabalin in this study were twice that of the FDA-approved maximal doses for diabetic neuropathy). Amitriptyline — by far the least expensive alternative — seems to be the winner here; however, many patients can't tolerate its anticholinergic side effects, and tricyclics are contraindicated in some patients with cardiac disease.