Combinations of Low-Dose Antidepressants and Low-Dose Pregabalin as Useful Adjuvants to Opioids for Intractable, Painful Bone Metastases

Background: Systemic analgesics would not provide good enough pain relief for some kindsof cancer pain. Metastatic bone pain is characteristic of one of the refractory cancer pains, sincethe pain is not only nociceptive but also neuropathic. A low-dose antiepileptic-antidepressantcombination with opioids is effective in the management of neuropathic cancer pain.Objective: The aim was to see whether a low-dose antiepileptic-antidepressant combination iseffective in the treatment of bone metastases.Study Design: Randomized, controlled trialSetting: Pain Clinic in Japan.Methods: Thirty-seven cancer patients, confirmed to have bone metastases, were allocatedinto 3 groups: P group took pregabalin 50 mg every 8 hours orally; P-I group took pregabalin 25mg every 8 hours orally and imipramine 5 mg every 12 hours orally; P-M group took pregabalin25 mg every 8 hours orally and mirtazapine 7.5 mg every 12 hours orally. Pain assessments wereperformed for 2 weeks.Results: The total pain score significantly decreased in all 3 groups even one day after the startof the medication. The decreases in the P-I and P-M groups were significantly greater than thosein the P group from Day 2. Also, the daily paroxysmal pain episodes significantly decreased in all3 groups at Day 1. The decreases in the P-M groups were significantly greater than those in theP group from Day 1. The decreases in the P-I group were significantly greater than those in the Pgroup from Day 3.Conclusion: Low-dose pregabalin-antidepressant combinations with opioids were effective inthe management of painful bone metastases.Key words: Cancer pain, painful bone metastases, antidepressant and anticonvulsants,pregabalin, mirtazapin