Sexual Side Effects with Vortioxetine
Vortioxetine has significantly lower rates of sexual dysfunction compared to traditional SSRIs and is not significantly different from placebo in causing sexual side effects. 1, 2
Evidence-Based Risk Profile
Vortioxetine demonstrates minimal sexual dysfunction risk across all phases of sexual response:
The FDA label explicitly states that vortioxetine may cause sexual dysfunction symptoms including ejaculatory delay/failure, decreased libido, and erectile dysfunction in males, and decreased libido with delayed/absent orgasm in females—however, clinical trial data show these rates are comparable to placebo 1
In a head-to-head randomized controlled trial in healthy adults, vortioxetine 10 mg showed significantly less sexual dysfunction than paroxetine (mean difference +2.74 points on CSFQ-14; P=0.009), while paroxetine caused significantly more sexual dysfunction than placebo 2
Pooled analysis of 7 clinical trials found that vortioxetine 5-20 mg/day had rates of treatment-emergent sexual dysfunction that were not significantly different from placebo, with vortioxetine 5 mg definitively non-inferior to placebo 3
Vortioxetine had significantly lower sexual dysfunction rates compared to duloxetine 60 mg/day in the same pooled analysis 3
Comparison to Traditional SSRIs
Vortioxetine's sexual side effect profile is dramatically more favorable than SSRIs:
When patients with well-treated depression experiencing SSRI-induced sexual dysfunction (from citalopram, paroxetine, or sertraline) were switched to vortioxetine versus escitalopram, vortioxetine showed significantly greater improvements in sexual function (CSFQ-14 score improvement: 8.8 vs 6.6; P=0.013) 4
Benefits were significant across four of five dimensions and all three phases of sexual functioning (desire, arousal, orgasm) compared to escitalopram 4
In real-world clinical practice, 83.81% of patients who switched to vortioxetine due to poorly tolerated antidepressant-related sexual dysfunction experienced improvement, with 43.2% reporting they felt "greatly improved" 5
Clinical Decision Algorithm
When sexual function is a concern in depression treatment:
First-line consideration: Vortioxetine (10-20 mg daily) or bupropion (significantly lower sexual dysfunction at 8-10% incidence) 6, 1
Avoid entirely: Paroxetine (70.7% sexual dysfunction rate—highest among all antidepressants) 7, 6
If already on an SSRI with sexual dysfunction: Switch to vortioxetine rather than another SSRI, as this strategy maintains antidepressant efficacy while improving sexual function 4, 5
Mechanism Explaining Lower Risk
Vortioxetine's multimodal mechanism accounts for its favorable sexual profile:
Unlike pure SSRIs, vortioxetine acts as an antagonist at 5-HT3, 5-HT1D, and 5-HT7 receptors, an agonist at 5-HT1A receptors, and a partial agonist at 5-HT1B receptors—this receptor profile suggests limited impact on sexual functioning 3, 8
The 5-HT3 receptor blockade produces increased levels of dopamine and norepinephrine in the prefrontal cortex, which may counteract the sexual dysfunction typically caused by serotonin reuptake inhibition alone 8
Critical Prescribing Considerations
The FDA mandates specific counseling about sexual function:
Prescribers must inquire about sexual function prior to initiating vortioxetine and specifically ask about changes during treatment, as sexual dysfunction may not be spontaneously reported 1
Obtain a detailed history including timing of symptom onset to distinguish medication effects from underlying psychiatric disorder 1
Discuss potential management strategies proactively to support informed treatment decisions 1
Dosing and Tolerability
Vortioxetine dosing for depression:
Therapeutic range: 10-20 mg once daily, with maximum dose of 20 mg daily 1, 8
Improvement in depressive symptoms typically noted at 2 weeks, with full therapeutic effect at 4-6 weeks 8
Most common adverse effect is nausea (not sexual dysfunction), followed by constipation and vomiting 1, 8
Nausea led to discontinuation in only 4.0% of patients in clinical trials 1
Important Caveats
Underreporting remains a concern:
Sexual dysfunction rates are vastly underreported in clinical trials across all antidepressants, with actual rates likely higher than published figures 6
Spontaneously reported sexual adverse events were low in vortioxetine trials despite systematic assessment showing measurable effects—emphasizing the need for active inquiry rather than waiting for patient reports 3
Treatment continuation rates after switching to vortioxetine are high (83.3%), suggesting real-world tolerability matches clinical trial data 5