Paroxetine (Paxil)

Class

SSRI (Selective Serotonin Reuptake Inhibitor)

Mechanism

Potent serotonin reuptake inhibitor (SERT) with strong affinity for muscarinic acetylcholine receptors (anticholinergic effects), contributing to sedative and cognitive side effects.

FDA-Approved Use

Major depressive disorder (MDD), panic disorder, generalized anxiety disorder (GAD), social anxiety disorder (SoAD), obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD)

Off-Label Use

Hot flashes, premenstrual dysphoric disorder (PMDD), post-stroke depression (PSD), post-stroke affective lability, depression in Parkinson’s disease (PD), agitation and aggression in neurodevelopmental disabilities

Formulation

Oral tablets, controlled-release tablets, and oral liquid solution (10 mg, 20 mg, 30 mg, 40 mg)

Titration

10–20 mg p.o. daily, titrating to 20–60 mg/day as tolerated

Dose Range

20–60 mg/day

Kinetics

Short half-life (~21 hours); metabolized primarily via CYP2D6; steady state in ~1 week

Common AEs

Sedation, weight gain, anticholinergic effects (dry mouth, constipation), sexual dysfunction, withdrawal symptoms with abrupt discontinuation

Serious/Rare AEs

Serotonin syndrome, hyponatremia, increased risk of bleeding

Monitoring

Monitor for serotonin syndrome, suicidality, and withdrawal symptoms during discontinuation

Black Box Warning

Increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults with MDD and other psychiatric disorders

Considerations

Paroxetine is generally avoided in older adults and patients with cognitive impairment due to its significant anticholinergic burden, which increases the risk of falls, delirium, and cognitive worsening. It may worsen fatigue or cognitive slowing in patients with multiple sclerosis (MS) or traumatic brain injury (TBI). Paroxetine is typically not a first-line agent in elderly or medically complex patients.