A COMPARISON OF AMITRIPTYLINE AND MAPROTILINE IN THE TREATMENT OF PAINFUL POLYNEUROPATHY IN DIABETICS AND NONDIABETICS

Objective: To compare amitriptyline and maprotiline in the treatment o f painful polyneuropathy in diabetics and nondiabetics. Design: A doub le-blind, crossover trial of treatment with amitriptyline, maprotiline , and placebo. Treatment was given in randomized order for periods of 4 weeks. Each period was separated by a 1-week washout. The final dose was 75 mg/day for both amitriptyline and maprotiline. Patients: Thirt y-seven patients with diabetic and nondiabetic painful polyneuropathy. Outcome Measures: The treatment effects were assessed by daily rating s of pain intensity on a 10-step verbal scale (0 = no pain and 10 = wo rst thinkable pain) and at the end of each treatment period by a globa l rating of the analgesic effect on a 5-step verbal scale (pain relief scale). For the assessment of depression, the Comprehensive Psychopat hological Rating Scale (CPRS) was used. Results: Using the global asse ssment of pain relief at the end of each treatment period, 22 of 33 pa tients reported reduced pain on amitriptyline treatment compared with 14 of 33 patients on maprotiline treatment and 8 patients on placebo t reatment (p < .0001 and p < .05 for amitriptyline and maprotiline, res pectively, against placebo). Amitriptyline line was slightly better th an maprotiline (p < .05) [tested by repeated measures analysis of vari ance (ANOVA)]. The order in which treatments occurred and the diagnosi s of diabetes or nondiabetes did not have any significant effect on th e global rating of pain relief. The mean values of the daily ratings o f pain intensity showed that pain was more severe in the evenings than in the mornings and that diabetic patients reported worse pain than n ondiabetics at baseline. The mean values of pain reduction as assessed with the 10-step verbal scale during the 4th week of treatment showed that amitriptyline and maprotiline were significantly better than pla cebo in relieving the pain (p < .0001 and p < .01, respectively, post hoc test according to Scheffe). However, there was no significant diff erence between the pain reduction of amitriptyline compared with mapro tiline when assessing pain reduction with the 10-step verbal scale dur ing the 4th treatment week. Nor was there a significant difference bet ween diabetics and nondiabetics with regard to the effect of the drugs . The clinical effect was not significantly correlated to plasma conce ntration of either amitriptyline and its active metabolite nortriptyli ne or maprotiline in the global or daily assessments. The effect of tr eatment was not correlated to any particular pain quality nor to the i ntensity of pain. Depression was noted in three patients who completed the medication trial, but the effect of treatment of pain and depress ion did not clearly correlate. The adverse side effects of amitriptyli ne and maprotiline were common, and in 5 patients the medication had t o be discontinued because of severe side effects. Conclusion: From the present results and the literature, it is concluded that tricyclic an tidepressants with a pharmacologic profile similar to amitriptyline ar e the most effective drugs in the treatment of polyneuropathy pain in both diabetic and nondiabetic patients.