Background Patients with benign prostatic hyperplasia (BPH) received α-blockers as first-line therapy to treat lower urinary tract symptoms (LUTS), but some individuals still experienced residual storage symptoms. Antimuscarinics, β3-agonists, and desmopressin are effective add-on medications. Nevertheless, currently there is no evidence for the appropriate choice of first add-on medication. The aim of this systematic review was to investigate the clinical benefits of antimuscarinics, β3-agonists, and desmopressin added to α-blockers for persistent storage symptoms in BPH patients.Methods A comprehensive literature search of randomized controlled trial (RCT) comparing the efficacy of different add-on medications for BPH patients with persistent storage symptoms despite α-blockers treatment was conducted. The clinical outcomes included the International Prostate Symptom Score (IPSS), IPSS storage sub-score, nocturia, micturition, and urgency. Network meta-analysis was performed to estimate the effect size. Surface under cumulative ranking curves (SUCRAs) were used to rank the included treatments for each outcome.Results A total of 15 RCTs were identified. Add-on imidafenacin or mirabegron showed significant improvement across all outcomes assessed. Other add-on medications of desmopressin, tolterodine, solifenacin, fesoterodine, and propiverine showed positive benefits for most but not all outcomes. Based on the SUCRA rankings, add-on desmopressin was related to the best ranked treatment for IPSS and nocturia, and add-on imidafenacin was the best for IPSS storage sub-score and micturition.Conclusions BPH patients presented with persistent storage symptoms despite α-blockers administration are recommended to received additional treatment. Desmopressin and imidafenacin may considered to be high-priority add-on treatment due to the superior efficacy than other medications.

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