What medications are similar to Trintellix (vortioxetine)?

Medications Similar to Trintellix (Vortioxetine)

Trintellix (vortioxetine) belongs to the class of second-generation antidepressants, and the most similar medication is vilazodone, which shares a comparable mechanism combining serotonin reuptake inhibition with 5-HT1A receptor partial agonism. 1

Medications in the Same Mechanistic Class

Vilazodone (Viibryd)

• Vilazodone is the closest alternative to vortioxetine, as both are selective serotonin reuptake inhibitors (SSRIs) with 5-HT1A receptor partial agonist activity 2, 3
• Like vortioxetine, vilazodone enhances serotonergic activity through selective serotonin reuptake inhibition while also acting as a partial agonist at 5-HT1A receptors 2, 3
• The recommended therapeutic dose is 40 mg daily with food, as absorption decreases by approximately 50% when taken without food 2
• Common adverse effects include diarrhea (26-29%), nausea (22-24%), vomiting (4-5%), and insomnia (6-7%) 2
• Vilazodone shows improvement in depressive symptoms within 1 week with increased remission rates at 6 weeks 3
• Sexual dysfunction rates are lower compared to traditional SSRIs due to the 5-HT1A partial agonist activity 3

Other Second-Generation Antidepressants

The American College of Physicians guidelines classify vortioxetine and vilazodone alongside other second-generation antidepressants (SGAs), which show no significant differences in efficacy for treating major depressive disorder 1. These include:

SSRIs (Selective Serotonin Reuptake Inhibitors)

• Citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline are all considered equivalent in efficacy to vortioxetine 1
• Selection should be based on adverse effect profiles, cost, and patient preferences rather than efficacy differences 1
• SSRIs have higher rates of sexual dysfunction compared to vortioxetine and vilazodone 1, 3

SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors)

• Venlafaxine, desvenlafaxine, duloxetine, and levomilnacipran are alternatives 1
• Head-to-head studies show no clinically significant difference between vortioxetine and SNRIs as a class for response or remission 4
• Duloxetine may be slightly more effective than vortioxetine for response rates, but vortioxetine has better tolerability with fewer adverse effects 4
• Venlafaxine showed no statistically significant differences compared to vortioxetine in two studies 4

Other Unique Mechanism Antidepressants

• Bupropion: The only antidepressant with no serotonergic activity; works on norepinephrine and dopamine; associated with lower sexual dysfunction rates 1, 3
• Mirtazapine: Enhances norepinephrine and serotonin by blocking alpha-2 presynaptic receptors; has faster onset (1-2 weeks) but causes sedation and weight gain 1, 3
• Trazodone: 5-HT2A/C antagonist and SSRI; primarily used off-label for insomnia at lower doses 3

Key Distinguishing Features of Vortioxetine

Vortioxetine has unique procognitive properties that distinguish it from other antidepressants, including vilazodone 5, 6:

• Vortioxetine improves objective cognitive measures (Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test) covering executive function, attention, processing speed, learning, and memory 5
• These cognitive benefits are largely independent of its effect on depressive symptoms 5
• Vortioxetine's multimodal mechanism includes antagonism at 5-HT3, 5-HT1D, and 5-HT7 receptors, agonism at 5-HT1A receptors, and partial agonism at 5-HT1B receptors 3, 6

Clinical Decision-Making Algorithm

When selecting an alternative to vortioxetine:

1. If procognitive effects are important: No other antidepressant has demonstrated comparable direct cognitive benefits; consider continuing vortioxetine or switching to vilazodone as the mechanistically closest alternative 5, 6, 7

2. If sexual dysfunction is a concern: Choose bupropion (lowest rates), vilazodone, or vortioxetine over traditional SSRIs 1, 3

3. If faster onset is needed: Mirtazapine shows improvement within 1-2 weeks versus 2-4 weeks for most SGAs 1, 3

4. If cost is a primary concern: Generic SSRIs (sertraline, citalopram, fluoxetine) are equivalent in efficacy 1

5. If treatment resistance occurs: The STAR*D trial showed no difference among bupropion, sertraline, and venlafaxine when switching after initial treatment failure; one in four patients became symptom-free after switching 1

Important Caveats

• All second-generation antidepressants require 6-8 weeks for adequate trial before modifying treatment 1
• Monitor closely for suicidality within the first 1-2 weeks of initiating any antidepressant, as SSRIs are associated with increased risk of suicide attempts 1
• 38% of patients do not achieve treatment response and 54% do not achieve remission with first-line SGA therapy, necessitating treatment modification 1
• When combining antidepressants with other serotonergic drugs, monitor for serotonin syndrome 2
• Vortioxetine and vilazodone both require dose adjustments when used with strong CYP3A4 inhibitors 2