Direct Answer: No, 98mg of Zoloft (sertraline) is NOT equivalent to 20mg of Trintellix (vortioxetine)
There is no established dose equivalence between sertraline and vortioxetine because they are fundamentally different antidepressants with distinct mechanisms of action, and no direct comparative studies exist to establish such equivalence. The comparison you're attempting is not clinically valid or supported by evidence.
Why This Comparison Cannot Be Made
Different Mechanisms of Action
Sertraline is a selective serotonin reuptake inhibitor (SSRI) that works primarily by blocking serotonin reuptake at the serotonin transporter 1
Vortioxetine is a multimodal antidepressant with multiple pharmacologic actions: it acts as a serotonin transporter blocker, 5-HT3 and 5-HT7 receptor antagonist, and 5-HT1A receptor agonist, modifying both glutamate and GABA release 2, 3, 4
These fundamentally different mechanisms mean that dose equivalence calculations used for comparing SSRIs to each other cannot be applied to vortioxetine 5
Absence of Comparative Data
The systematic dose equivalence study that established sertraline 98.5mg as equivalent to fluoxetine 40mg did not include vortioxetine because no randomized controlled trials directly comparing these medications exist 5
Vortioxetine was approved more recently and has not been included in the flexible-dose comparative trials needed to establish dose equivalence 3
What We Know About Each Medication
Sertraline Dosing
- Therapeutic dose range: 50-200mg daily 1
- Mean steady-state plasma concentration at 50mg/day: 12±17 ng/mL (geometric mean) 1
- At 100mg/day: 19±18 ng/mL (geometric mean) 1
Vortioxetine Dosing
- Therapeutic dose range: 5-20mg daily 2, 3
- Recommended starting dose: 10mg once daily 3
- The drug displays high affinity for serotonin transporter and multiple serotonin receptor subtypes 3
Clinical Implications
If Switching Between These Medications
Cross-titration is required rather than direct dose substitution 1
When switching from sertraline to vortioxetine, taper sertraline gradually over 10-14 days minimum while initiating vortioxetine at its standard starting dose of 10mg 6
Monitor for withdrawal symptoms from sertraline (irritability, agitation, dizziness, sensory disturbances) and new side effects from vortioxetine (nausea, headache) 6, 2
Efficacy Considerations
Both medications are effective for major depressive disorder, but vortioxetine has demonstrated unique procognitive effects not typically seen with SSRIs like sertraline 2, 3
Vortioxetine may be more effective than SSRIs for cognitive symptoms of depression, which represents a distinct therapeutic advantage rather than simple dose equivalence 2
Second-generation antidepressants including sertraline show no significant differences in overall efficacy for depression, but individual response varies 1
Common Pitfall to Avoid
Do not attempt to calculate dose equivalence between different antidepressant classes (SSRI vs. multimodal agent) using ratios derived from within-class comparisons. The dose equivalence methodology only applies when comparing drugs with similar mechanisms of action through head-to-head flexible-dose trials 5. Vortioxetine's multimodal mechanism makes such comparisons invalid and potentially dangerous for clinical decision-making.