Efficacy and safety of drug combinations for chronic pelvic pain: a systematic review.

Clinical disorders associated with chronic pelvic pain (CPP) cause demonstrable emotional and physical dysfunction as well as increased health care utilization. Interventions that have been studied for the treatment of CPP often provide inadequate relief and/or intolerable adverse effects. The common practice of combining multiple CPP treatments needs more supportive evidence, and emerging combination trials have been evaluated in this systematic review. We searched MEDLINE and EMBASE and CENTRAL databases for CPP combination trials. This review included double-blind randomized controlled trials comparing combinations of 2 or more agents to at least 1 monotherapy in adults with CPP. The primary outcome was reduction in pain intensity or pain relief, and secondary outcomes included adverse events, quality of life, and other symptoms. Risk of bias was assessed. Nine studies (1,299 participants) were included and involved various different treatments including ciprofloxacin, tamsulosin, pentosan polysulfate, hyaluronic acid, chondroitin, hydroxyzine, troxerutin, carbazochrome, linzagolix, and allopurinol. Studies were heterogenous according to several features including studied treatments, dose and route of administration, and underlying condition such that no studies could be combined for meta-analysis. None of the included studies reported a significant difference in reducing pain intensity for combination therapy vs monotherapy. If future proof-of-concept studies demonstrate that a given combination is superior to all monotherapy components, subsequent large, double-blind randomized, controlled clinical trials of such combinations for CPP are required to better elucidate the role of combination therapy in clinical settings.