A Randomized, Placebo-Controlled Study of Duloxetine for Pain in Multiple Sclerosis

Background: Pain is one of the most common and disturbing symptoms of MS.  Duloxetine is a serotonin norepinephrine reuptake inhibitor with analgesic properties in other conditions.  Duloxetine has a potential therapeutic role in treating MS related pain. 

Objectives: To determine whether duloxetine is effective in relieving central pain in MS, as measured by a reduction in the weekly 24-hour worst pain score.

Methods: 38 MS patients were randomized 1:1 to receive Duloxetine  (n=18) or matched Placebo (n=20). Dosing regimen was 30mg daily for one week, then 60mg daily for five weeks.  Patients kept daily pain diaries throughout the study.  The primary outcome measure was change in Worst pain for Week 6 relative to baseline.  Scores for average and worst pain were recorded at baseline, 1, 2, 4 and 6 weeks post baseline.  Secondary outcomes included Beck Depression Inventory (BDI), Sleep Quality Score, SF-36. 

Results: Of the 38 randomized patients, average age was 56.3 years, 24% were male, and 63.2% had RRMS.  Baseline characteristics were similar except for baseline disease-modifying drug use, which was 94% for Duloxetine and 55% for placebo (p=0.009).  For both groups, the lower limbs were the most commonly reported pain locations.  Fourteen (78%) patients randomized to Duloxetine and 19 (95%) randomized to placebo completed treatment, and discontinuations were due primarily to drug intolerance.  Among those who completed treatment, Worst pain at 6 weeks was reduced by 29% (± 20%) for Duloxetine vs. 12% (± 18%) for placebo (p=0.016). Average daily pain at 6 weeks was reduced by 39% (± 29%) on Duloxetine compared to 10% ( ± 18.8) in the placebo group (p=0.002). Patients randomized to Duloxetine also had significantly greater reductions in average daily pain at weeks 2 and 4, and in worst daily pain at week 4.  There were no significant changes (week 6 vs. baseline) or between-group differences for BDI, SF-36 or Sleep Quality. 

Conclusions: (1) Fewer patients could tolerate Duloxetine compared to placebo. (2) Among patients who completed 6 weeks of treatment, there were significant reductions in average and worst daily pain scores on Duloxetine compared to placebo.   The difference in pain reduction was not associated with change in depression, sleep or overall quality of life.  This study suggests that duloxetine has a direct pain-relieving effect in MS.