Comparative Efficacy of Pharmacological Interventions for Chronic Prostatitis/Chronic Pelvic Pain Syndrome: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent and debilitating urological condition affecting approximately 2–10% of men globally, with a substantial impact on quality of life, productivity, and healthcare utilization. Despite the availability of multiple pharmacological options, their comparative efficacy remains uncertain. This meta-analysis evaluated the efficacy of pharmacological interventions for CP/CPPS based on the NIH-Chronic Prostatitis Symptom Index (NIH-CPSI). Methods: A systematic search of PubMed, Scopus, ScienceDirect, and Google Scholar was conducted from database inception to January 2025 for randomized controlled trials (RCTs) comparing pharmacological therapies with placebo. The primary outcome was a mean reduction in NIH-CPSI total score, with a clinically meaningful improvement defined as a ≥6-point reduction. Pooled mean differences (MDs) with 95% confidence intervals (CIs) were calculated using random-effects models, and risk of bias was assessed using the Cochrane Risk of Bias tool. The certainty of evidence was evaluated using the GRADE approach. Results: Alpha-blockers demonstrated the most consistent benefit (MD: −5.13; 95% CI: −6.87 to −3.39; Low certainty), followed by Traditional Chinese Medicine (TCM) (MD: −3.14; 95% CI: −5.38 to −0.90; Low certainty) and analgesics (MD: −2.47; 95% CI: −4.24 to −0.70; Low certainty). In contrast, antibiotics (MD: −2.45; 95% CI: −5.53 to 0.64; Very Low certainty), pollen extracts (MD: −2.56; 95% CI: −10.83 to 5.71; Very Low certainty), and other agents such as botulinum toxin A and anticonvulsants (MD: −6.94; 95% CI: −19.79 to 5.91; Very Low certainty) did not achieve statistical significance. The certainty for all interventions was downgraded from High due to risk of bias and substantial heterogeneity (I² > 75%). Funnel plot asymmetry suggested potential publication bias; however, Egger’s test did not confirm statistical significance (p = 0.626). Conclusions: Among available pharmacological options, alpha-blockers and TCM provide the most reliable symptom improvement in men with CP/CPPS, while analgesics offer modest benefit. Antibiotics, pollen extracts, and other agents show inconsistent or non-significant effects. The high heterogeneity and generally low certainty of evidence reflect variability in study quality and populations, underscoring the need for rigorously designed, standardized future trials to guide patient-centered therapy selection.