Venlafaxine More Effectively Treats Symptoms of Major Depressive Disorder After Menopause Than Fluoxetine

Side view of elderly asian woman with thoughtful face expression
To date, there has not been proven evidence for serotonin-norepinephrine reuptake inhibitors over selective serotonin reuptake inhibitors in postmenopausal patients with major depressive disorder. Consequently, study researchers aimed to compare the efficacy and safety of venlafaxine vs fluoxetine in the treatment of postmenopausal MDD.

Venlafaxine was more successful than fluoxetine at treating major depressive disorder (MDD) among patients who were postmenopausal, according to results of a multicenter, randomized, single-blind, active-controlled trial published in BMC Psychiatry.

Patients with MDD were recruited at the Beijing Anding Hospital and Beijing Chaoyang Hospital between 2013 and 2017. Patients were randomized in a 1:1 ratio to receive 20-60 mg/d fluoxetine (n=90) or 75-255 mg/d venlafaxine (n=82) for 8 weeks. The primary endpoint was change in Hamilton Depression Rating Scale (HAMD-24) scores and secondary endpoints were change in anxiety and somatization factor scores and Clinical Global Impressions-Improvement (CGI-I) scores.

The venlafaxine and fluoxetine cohorts comprised patients who were aged 56.7±6.8 and 56.9±5.8 years, BMI was 23.9±3.8 and 23.0±2.9 kg/m2, MDD onset at 52.3±7.9 and 51.5±8.2 years of age, HAMD-24 scores were 30.5±7.3 and 31.7±8.5 points, and CGI-I scores were 3.7±1.2 and 3.7±1.0 points, respectively.

At 8 weeks HAMD-24 scores were more greatly reduced among venlafaxine recipients (F[1,144], 12.0; P =.001) with a least-squares mean difference of -2.22 (95% CI, -7.08 to -0.41) points.

Total anxiety and somatization factor scores were more greatly reduced among the venlafaxine recipients (F[1,137], 14.5; P <.001) with a least-squares mean difference of -2.33 (95% CI, -2.25 to -0.19) points. CGI-I response was observed among 68.9% of the venlafaxine group and 48.5% of the fluoxetine cohort (P =.019).

Treatment-emergent adverse events were observed among 27.0% of the venlafaxine and 32.3% of the fluoxetine recipients (P =.435) of which 18.0% and 26.9% were deemed to be related with the study drug (P =.151), respectively. All events were mild or moderate including nausea (15.7%), somnolence (6.7%), and dizziness (5.6%) for venlafaxine and nausea (11.8%), dry mouth (7.5%), dizziness (6.5%), and headache (5.4%) for fluoxetine.

This study may have been limited by the choice to not monitor changes in estrogen levels throughout the course of the trial.

The study authors concluded 8 weeks of venlafaxine more effectively treated the symptoms of MDD among patients who were postmenopausal than fluoxetine. Both study drugs were well-tolerated.

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Zhou J, Wang X, Feng L, et al. Venlafaxine vs. fluoxetine in postmenopausal women with major depressive disorder: an 8-week, randomized, single-blind, active-controlled study. BMC Psychiatry. Published online May 19, 2021. doi:10.1186/s12888-021-03253-8