BACKGROUND: Existing meta-analytic evidence on bipolar mania treatment has revealed that augmentation therapy (AUG) with antipsychotics (AP) and mood stabilizers (MS) is more effective than monotherapy. However, the speed of the onset of treatment effects and subsequent changes in risk/benefit are unclear. METHODS: We searched the Cochrane CENTRAL, MEDLINE, and EMBASE databases until January 2021. Our primary outcomes were response and tolerability. We set three time points:1, 3, and 6 weeks after randomization. RESULTS: Seventeen studies compared AUG therapy and MS monotherapy (comparison 1), and eight studies compared AUG therapy and AP monotherapy (comparison 2). In comparison 1, AUG therapy resulted in significantly more responses than monotherapy, with an odds ratio (OR) of 1.45 (95% confidence interval [CI]: 1.17 to 1.80) at 3 weeks and 1.59 (95%CI: 1.28 to 1.99) at 6 weeks. Significant improvement was observed in the first week with a standardized mean difference (SMD) of -0.25 (95%CI: -0.38 to -0.12). In comparison 2, AUG therapy was significantly more effective than monotherapy, with an OR of 1.73 (95%CI: 1.25 to 2.40) at 3 weeks and 1.74 (95%CI: 1.11 to 2.73) at 6 weeks. Significant improvement was observed in the first week with an SMD of -0.23 (95%CI: -0.39 to -0.07). Regarding tolerability, there was no significant difference between AUG therapy and monotherapy at 3 and 6 weeks in both comparisons. CONCLUSIONS: Early AUG therapy should be considered, as it has shown efficacy from weeks 1 to 6, although attention to side effects is necessary for acute mania treatment.