Nishihara, M., Arai, Y.C., Yamamoto, Y., Nishida, K., Arakawa, M., Ushida, T., & Ikeuchi, M. (2013). Combinations of low-dose antidepressants and low-dose pregabalin as useful adjuvants to opioids for intractable, painful bone metastases. Pain Physician, 16, E547–E552.

To see if a combination of low-dose antidepressants and antiepileptic is effective in treatment of pain from bone metastases

Patients were randomized to one of three groups: pregabalin 50 mg every 8 hours (P), pregabalin 25 mg every 8 hours and imipramine 5 mg every 12 hours (PI), or pregabalin 25 mg every 8 hours and mirtazapine 7.5 mg every 12 hours (PM). Assessments were done at baseline and daily between days 1–7 and on days 10–14.

• N = 27  
• MEAN AGE = 58 years
• AGE RANGE = 37–77 years
• MALES: 75%, FEMALES: 25%
• KEY DISEASE CHARACTERISTICS: All had confirmed bone metastases.
• OTHER KEY SAMPLE CHARACTERISTICS: Baseline pain scores were higher than 6 on scale of 0–10. Across groups, the daily opioid dose in morphine equivalents was 57.5 (range = 20–200). All patients were receiving bisphosphonates and loxoprofen.

• SITE: Single site   
• SETTING TYPE: Outpatient   
• LOCATION: Japan

• PHASE OF CARE: Late effects and survivorship
• APPLICATIONS: Palliative care

• Three-group randomized trial

• Numeric pain scale (0–10)

Total pain scores decreased significantly on day 1 in all groups (p < .05). By day 2, pain scores declined significantly more in the PI and PM groups and remained essentially stable and consistently lower than the P group (p < .05). A few patients developed dizziness and mild drowsiness. No changes were seen in electrocardiograms.

The combination of low-dose pregabalin and low-dose antidepressant significantly reduced pain in this study.

• Small sample (less than 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias(sample characteristics)
• Other limitations/explanation: The baseline daily opioid dose varied widely, and the overall average was relatively low for intractable pain. The timing of assessments varied, and only very short-term results are stated. The study did not have a control group.

Findings suggest that the combination of low-dose antidepressant and antiepileptic medication as adjuncts to opioids and bisphosphonates may improve pain control in patients with intractable pain from bone metastases. This type of combination may be worth trial in patients with this type of pain. Nurses should be aware of the potential for drug-drug interactions in patients taking multiple medications. This potential may be less with low doses, as used in this study.