Phase 2 Trial Finds Ammoxetine Safe and Effective for Adults With MDD
Ammoxetine significantly reduced depressive symptoms and was well-tolerated in adult patients with major depressive disorder (MDD), according to phase 2 trial results published in JAMA Network Open.
“Although several first-line treatments [for MDD] exist with mild adverse effects, up to 50% to 60% of patients do not tolerate or respond to them,” wrote Shen He, MD, Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China, and study coauthors. “Ammoxetine, a novel selective serotonin and norepinephrine reuptake inhibitor, has been found to reduce adverse effects and hepatotoxicity and more potent inhibition of serotonin and norepinephrine transporters, making it more tolerable and effective.”
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The randomized clinical trial recruited 239 patients between ages 18 and 65 years with MDD from 15 study centers in China. Participants were randomized to receive either 40 mg/d of ammoxetine (n=80), 60 mg/d of ammoxetine (n=80), or placebo (n=79). Researchers measured the change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline to 8 weeks and recorded the rate of treatment-emergent adverse events (TEAEs) to evaluate safety.
Both the 40 mg and 60 mg groups saw significantly improved MADRS scores at 8 weeks compared with placebo. The least-squares mean changes (SE) from baseline were −16.7 (1.3) for the ammoxetine 40 mg group, −16.6 (1.3) for the ammoxetine 60 mg group, and −13.5 (1.3) for placebo.
In terms of safety, the rate of TEAEs was 85.0% in the 60 mg/d group and 78.8% in the 40 mg/d group. “These rates align with a meta-analysis reporting TEAE rates of 73.3% to 73.6% for escitalopram and 78.2% for other SSRIs, alongside 77.4% for SNRIs (including venlafaxine and duloxetine),” the researchers noted.
The researchers also pointed out that the ammoxetine exhibited lower discontinuation rates than other antidepressant drugs. No patients discontinued treatment due to liver function abnormalities or sexual dysfunction, common complications of other antidepressant medications.
“These results support the need for further phase 3 trial investigations, which should involve larger samples,” the authors concluded.