1. 2013;16;E547-E552Combinations of Low-Dose Antidepressants and Low-Dose Pregabalin as Useful Adjuvants to Opioids for Intractable, Painful Bone Metastases
   Randomized Trial
   Makota Nishihara, MD, Young-Chang P Arai, MD, Yoshihiro Yamamoto, MD, Kikuyo Nishida, MD, Maki Arakawa, MD, Takahiro Ushida, MD, and Masahiko Ikeuchi, MD.

BACKGROUND:  Systemic analgesics would not provide good enough pain relief for some kinds of cancer pain. Metastatic bone pain is characteristic of one of the refractory cancer pains, since the pain is not only nociceptive but also neuropathic. A low-dose antiepileptic-antidepressant combination with opioids is effective in the management of neuropathic cancer pain.
OBJECTIVE:  The aim was to see whether a low-dose antiepileptic-antidepressant combination is effective in the treatment of bone metastases.
STUDY DESIGN: Randomized, controlled trial
SETTING:  Pain Clinic in Japan.
METHODS: Thirty-seven cancer patients, confirmed to have bone metastases, were allocated into 3 groups: P group took pregabalin 50 mg every 8 hours orally; P-I group took pregabalin 25 mg every 8 hours orally and imipramine 5 mg every 12 hours orally; P-M group took pregabalin 25 mg every 8 hours orally and mirtazapine 7.5 mg every 12 hours orally. Pain assessments were performed for 2 weeks.
RESULTS: The total pain score significantly decreased in all 3 groups even one day after the start of the medication. The decreases in the P-I and P-M groups were significantly greater than those in the P group from Day 2. Also, the daily paroxysmal pain episodes significantly decreased in all 3 groups at Day one. The decreases in the P-M groups were significantly greater than those in the P group from Day one. The decreases in the P-I group were significantly greater than those in the P group from Day 3.
CONCLUSION: Low-dose pregabalin-antidepressant combinations with opioids were effective in the management of painful bone metastases.