Efficacy and Safety of Ammoxetine in Major Depressive Disorder

1. Ammoxetine, a novel SNRI developed from duloxetine, was effective at treating adults with major depressive disorder (MDD) and was safe and well-tolerated.

Evidence Rating Level: 1 (Excellent)

The World Health Organization estimates that (MDD) will become the primary cause of disability worldwide by 2030. While selective serotonin re-uptake inhibitors (SSRIs) and selective serotonin and norepinephrine re-uptake inhibitors (SNRIs) are often recommended as first-line therapy given their relatively safe biochemical profile, unfortunately only 30-40% of patients reach remission with these medications. SNRIs may be more efficacious than SSRIs although there is a limited variety of SNRIs. Thus, there is a need for new medications within this class. This phase 2, multicenter, placebo-controlled, parallel-group study investigated the efficacy and safety of ammoxetine, a novel SNRI developed from duloxetine which has demonstrated promising efficacy and safety profiles in phase 1 trials. 239 adults with MDD were randomized in a 1:1:1 ratio to receive ammoxetine 60 mg/day, ammoxetine 40 mg/day, or placebo. Compared to placebo, both ammoxetine 60 mg/day and 40 mg/day significantly decreased Montgomery-Åsberg Depression Rating Scale (MADRS) scores (97.3% CI, −6.2 to 0.0; P = .02 and 97.3% CI, −6.3 to −0.3; P = .02, respectively) after 8 weeks of treatment. However, there was no significant difference in remission rates of MADRS or scores as assessed by the Hamilton Rating Scale for Depression or Clinical Global Impressions-Severity scale. The side effects of constipation, parageusia, weight loss, hyperhidrosis, decreased appetite, dry mouth, diarrhea, dizziness, and nausea were present in at least twice as many patients in the intervention groups as in the placebo group. Notably, no patients discontinued treatment due to sexual dysfunction. Overall, this study found that ammoxetine is effective at treating MDD safe, and generally well tolerated, although further trials with larger samples are required.

Click here to read this study in JAMA Network Open

Image: PD

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