Table 1. Comparison of Bupropion and Other Antidepressants in Major Depressive Disorder.

Study	Drug Comparison with Mechanism of Action	Study Design	MADRS Change from Baseline to Study Endpoint	Conclusions
Koshino (2022) The efficacy and safety of bupropion sustained-release formulation for the treatment of major depressive disorder: a multi-center, randomized, double-blind, placebo-controlled study in Asian patients53	Bupropion vs Placebo	Double-blind, randomized placebo-controlled trial 569 Asian patients with a diagnosis of Major Depressive Disorder were treated with 125mg or 300 mg of Bupropion vs placebo over a period of 8 weeks.	Bupropion (150mg): -14.4 Bupropion (300mg): -12.9 Placebo: -13.9 Mean Difference (BU150): -0.5 95% CI: -2.7, 1.7 P-Value: .853 Mean Difference (BU300): N/A 95% CI: N/A	Bupropion did not exhibit significant improvement in MDD symptoms compared to placebo.
Tabuteau (2022) Effect of AXS-05 (Dextromethorphan-Bupropion) in Major Depressive Disorder: A Randomized Double-Blind Controlled Trial54	AXS-05 Bupropion 105mg + Dextromethorphan 45mg Non-competitive NMDA Antagonist	Double bind, randomized controlled trial 80 patients with the diagnosis of Major Depressive Disorder were randomized into groups receiving AXS-05 and bupropion (105 mg) over a period of 6 weeks.	AXS-05: -13.7 Bupropion: -8.8 Least-squares mean difference: -4.9 95% CI: -3.1, -6.8 P-Value: <.0001	Both AXS-05 and Bupropion were effective at reducing MDD symptoms with AXS-05 having a slightly greater effect.
Iosifescu (2022) Efficacy and Safety of AXS-05 (Dextromethorphan-Bupropion) in Patients With Major Depressive Disorder: A Phase 3 Randomized Clinical Trial (GEMINI)55	AXS-05 vs Placebo	Double bind, randomized placebo-controlled trial 327 patients with DSM-5 diagnosis of MDD were randomized to receive placebo or AXS-05 for 6 weeks.	AXS-05: -15.9 Placebo: -12.0 Least-squares mean difference: -3.9 95% CI: -1.4, -6.4 P-Value: .002	AXOS-05 exhibited significantly greater improvements in all outcomes measured at all time points including MADRS score when compared to placebo.
Shen (2019) Efficacy and safety of bupropion hydrochloride extended-release versus escitalopram oxalate in Chinese patients with major depressive disorder: Results from a randomized, double-blind, non-inferiority trial56	Bupropion vs Escitalopram Selective Serotonin Reuptake Inhibitor (SSRI)	Double bind, randomized controlled trial 534 patients in China with the diagnosis of MDD were randomized to receive 150-300mg of Bupropion extended release or 10-20mg of Escitalopram for 8 weeks.	Escitalopram: -19.5 Bupropion: -18.6 Least-squares mean difference: 0.9 95% CI: -.69, 2.4 P-Value: .278	Bupropion was non-inferior to escitalopram when treating major depressive symptoms in an outpatient setting after eight weeks.

AXOS-05: 45mg Dextromethorphan + 105mg Bupropion

HAMD-17: Hamilton Depression Rating Scale-17

MADRS: Montgomery-Asberg Depression Rating Scale

MDD: Major Depressive Disorder