Abstract Introduction Olanzapine is an established antiemetic for the prevention of chemotherapy-induced nausea and vomiting (CINV), although the optimal dose for balancing efficacy and tolerability remains uncertain. We conducted a systematic review and network meta-analysis comparing olanzapine 2.5 mg, 5 mg, and 10 mg for CINV prophylaxis. Methods PubMed, Embase, and Cochrane CENTRAL were searched from inception to April 9, 2026 for randomized controlled trials evaluating olanzapine for CINV prophylaxis in adults receiving chemotherapy. A frequentist random-effects network meta-analysis was performed. Primary outcomes included complete response during the acute, delayed, long-delayed, and overall phases. Secondary outcomes included complete control, no nausea, no vomiting, and safety outcomes. Results A total of 54 randomized controlled trials involving 10,455 participants were included. Olanzapine-containing regimens consistently improved complete response, complete control, no nausea, and no vomiting outcomes compared with placebo-controlled regimens across all phases of CINV. Olanzapine 10 mg generally demonstrated the numerically largest efficacy estimates. However, direct comparisons between olanzapine 10 mg and 5 mg did not demonstrate statistically significant differences across efficacy outcomes, suggesting preserved efficacy with dose reduction. In highly emetogenic chemotherapy populations, olanzapine 5 mg demonstrated efficacy comparable to olanzapine 10 mg. In moderately emetogenic chemotherapy populations, olanzapine 5 mg consistently improved outcomes compared with placebo-controlled regimens. Dose reduction from olanzapine 10 mg to 5 mg was not clearly associated with lower sedation risk. Evidence for olanzapine 2.5 mg remained very limited but suggested the possibility of preserved efficacy with lower toxicity. Conclusions Olanzapine-containing regimens significantly improved prevention of CINV. Olanzapine 5 mg appeared to preserve substantial efficacy relative to olanzapine 10 mg, although dose reduction did not clearly reduce sedation risk. Additional randomized trials are needed to further define the optimal olanzapine dose.
Chow et al. (Thu,) studied this question.