Slowing the initial titration rate of tramadol improves tolerability

Study Objectives. To examine the effect of three titration schedules on the tolerability of tramadol, and to determine whether slow titration would reduce the frequency of drug discontinuation due to adverse events. Design. Multicenter, outpatient, double-blind, parallel study. Setting. Twenty-eight outpatient study centers. Subjects. Four hundred sixty-five patients with chronic joint pain Interventions. Patients were randomized into one of four treatment groups for 14 days: placebo, or tramadol dosage titrated at 1, 4, or 10 days to achieve the study target dosage of 200 mg/day. They continued taking their dosage of nonsteroidal antiinflammatory drug during the study. Each group was examined to determine if slower titration resulted in a statistically significant trend toward fewer discontinuations due to nausea and/or vomiting and dizziness and/or vertigo. Discontinuation due to any adverse event was similarly analyzed. If the trend was statistically significant, pairwise comparisons were performed to determine the statistical significance among titration rates. Measurements and Main Results. A statistically significant trend was seen toward fewer discontinuations as a result of nausea/vomiting, dizziness/vertigo, and any adverse event as the titration rate decreased. Patients with 10-day titration rate required the fewest discontinuations, and this rate was statistically significantly different from both the 1- and 4-day rates for discontinuations. Conclusion. A slower rate of initiating tramadol therapy (50-mg increments every 3 days) improved tolerability with significantly fewer discontinuations due to dizziness or vertigo.