Sertraline vs Paroxetine
## Overview
Sertraline and paroxetine are both widely prescribed SSRIs with broad anxiety and depression indications, but sertraline is generally preferred due to paroxetine's unfavorable tolerability profile and teratogenicity risk.
## Mechanism of Action
Both block SERT. Paroxetine additionally antagonizes muscarinic receptors, contributing to anticholinergic side effects. Paroxetine also inhibits norepinephrine reuptake weakly.
## Pharmacokinetics
Sertraline: half-life 26 h, minimal CYP inhibition, linear pharmacokinetics. Paroxetine: half-life 21 h, very potent CYP2D6 inhibitor with auto-inhibition causing nonlinear dose-concentration relationship.
## Pharmacodynamics
Equivalent antidepressant efficacy. Paroxetine's anticholinergic properties may provide some additional anxiolytic benefit but at the cost of side effects (cognitive blunting, weight gain, sexual dysfunction — paroxetine has the highest incidence of sexual dysfunction of any SSRI).
## Safety Considerations
Paroxetine is contraindicated in pregnancy (cardiac teratogen), causes the most severe SSRI discontinuation syndrome, and has the most drug interactions. Sertraline is FDA Pregnancy Category C (PLLR: potential fetal risk, benefit may outweigh risk), preferred in pregnant patients requiring an SSRI.
## Key Takeaways
- Both effective for MDD, OCD, panic, PTSD, social anxiety, PMDD
- Sertraline: fewer interactions, less weight gain, less sexual dysfunction, safer in pregnancy
- Paroxetine: most discontinuation syndrome, anticholinergic burden, worst sexual dysfunction
Fazit
Sertraline is preferred over paroxetine in most clinical situations. Paroxetine may be appropriate as a second-line agent for treatment-resistant anxiety when other SSRIs have failed, but its tolerability and safety limitations should be weighed carefully.