Background/Purpose: The two treatment options that have received the significant attention in fibromyalgia (FM) management are cognitive behavioral therapy (CBT) and medications. Given the fact that either therapy alone appears to only produce modest improvements in clinical symptoms, we completed a 3-arm randomized attention-controlled trial whose primary aim was to obtain preliminary estimates of the effects of combined CBT and milnacipran on primary clinical endpoints: changes in weekly average pain intensity (daily electronic recording of pain scores) and physical function (SF-36 physical component summary score).

Methods: Fifty eight patients with FM were randomized to one of the 3 treatment arms: (1) combination therapy (n=20), (2) drug + education attention (n=19), and (3) placebo + CBT (n=19). Throughout the 21-week study, subjects received either milnacipran (50 mg BID) or placebo (BID). Subjects also received 8 sessions of telephone-delivered CBT or educational instructions, but only from baseline to week 9. Assessments were conducted at baseline, week 9 and 21. Secondary clinical endpoints included changes in PHQ-8 depression severity (0-24), and evoked (thumb) pressure pain scores (0-20), a measure of pain sensitivity.

Results: Characteristics of the 58 FM subjects: mean age= 46.6 (10.4) years; female=93%; whites= 81%; high school graduates=71%; concomitant opioid analgesics=43%; PHQ-8 depression=10.55 (4.79); evoked pressure pain= 8.8 (0.59); weekly average pain intensity = 6.31 (1.27); and SF-36 physical function= 45.26 (22.4).

Compared to drug alone, combination therapy demonstrated a medium effect on reducing weekly average pain intensity (effect size/ES=0.67) and in improving SF-36 physical function (ES=0.60). The magnitude of change in the pain intensity score in the combination group was more than twice the magnitude of change in the drug monotherapy group.  Compared to drug alone, CBT alone was marginally efficacious in improving SF-36 physical function. No significant between group differences were seen in improvement in depression severity and change in evoked pain scores. Interestingly, subjects in the drug groups (i.e., combination and drug alone) became less sensitive to pressure stimuli compared to subjects in the CBT monotherapy group, albeit this difference was not statistically significant.

Table 1.

D: Baseline to week 21 change in the specified variable; Values represent means and standard error

† Significant within group difference (p<0.04)

Conclusion: Based on the observed effect sizes, our preliminary data justifies pursuing a larger definitive trial to test the superiority of combination therapy vs. monotherapy.  Additionally, a direct comparison of CBT vs. drug monotherapy is warranted to inform future health care decisions.