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.

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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