Paroxetine vs Citalopram

## Overview

Paroxetine and citalopram are both SSRIs but occupy very different positions in clinical practice. Citalopram is considered among the cleanest SSRIs pharmacologically, while paroxetine has the most complex off-target profile.

## Mechanism of Action

Both inhibit SERT. Paroxetine also blocks muscarinic receptors (anticholinergic), inhibits norepinephrine reuptake weakly, and has the highest SERT affinity of classical SSRIs. Citalopram's pharmacology is essentially limited to SERT inhibition.

## Pharmacokinetics

Paroxetine: half-life ~21 h, potent CYP2D6 inhibitor with auto-inhibition (nonlinear PK). Citalopram: half-life ~35 h, minimal CYP inhibition, linear PK, CYP2C19-dependent.

## Safety Profile

Paroxetine's anticholinergic burden causes cognitive side effects, constipation, dry mouth, and urinary retention — problematic in elderly patients. Its severe discontinuation syndrome (often described as "brain zaps," dizziness, nausea) is unmatched among SSRIs. Citalopram's main safety concern is QTc prolongation, managed with dose capping at 40 mg. Paroxetine is Pregnancy Category D; citalopram is Category C.

## Clinical Use

Citalopram is the SSRI most often used by non-psychiatrists (primary care) due to its simplicity and tolerability. Paroxetine is less commonly initiated due to its side effect burden, but may be considered for severe anxiety or OCD when other SSRIs have failed.

## Key Takeaways

- Citalopram: clean pharmacology, QTc concern, max 40 mg, preferred in primary care
- Paroxetine: most off-target effects, severe discontinuation, worst in pregnancy, avoid in elderly
- Both equivalent in antidepressant efficacy