Paxil (Paroxetine): Medication Overview
Paxil is the brand name for paroxetine hydrochloride, a selective serotonin reuptake inhibitor (SSRI) antidepressant that is FDA-approved for treating multiple psychiatric conditions including major depressive disorder, obsessive-compulsive disorder, panic disorder, social anxiety disorder, generalized anxiety disorder, and posttraumatic stress disorder. 1
Drug Classification and Mechanism
- Paroxetine is the most potent inhibitor of serotonin reuptake among all currently available SSRIs, working by selectively blocking the reuptake of serotonin (5-HT) in the central nervous system 2, 3
- It is a phenylpiperidine derivative with minimal effects on norepinephrine, dopamine, or histamine systems, resulting in fewer autonomic side effects compared to tricyclic antidepressants 3
- The drug has some anticholinergic activity at muscarinic receptors, though significantly less than older antidepressants 3
FDA-Approved Indications
Paxil is approved for the broadest range of anxiety disorders among all SSRIs, making it particularly valuable when treating comorbid depression and anxiety 2, 1:
- Major Depressive Disorder (MDD)
- Obsessive-Compulsive Disorder (OCD)
- Panic Disorder (with or without agoraphobia)
- Social Anxiety Disorder (Social Phobia)
- Generalized Anxiety Disorder (GAD)
- Posttraumatic Stress Disorder (PTSD)
- Premenstrual Dysphoric Disorder 2
Formulations and Dosing
- Available as immediate-release tablets (10 mg, 20 mg, 30 mg, 40 mg) and oral suspension (10 mg/5 mL) 1
- A controlled-release formulation (Paxil CR) was developed to improve gastrointestinal tolerability 4
- Typical dosing ranges from 10-60 mg daily depending on the condition being treated 2
Critical Safety Warnings
The FDA has issued a black box warning for treatment-emergent suicidality, particularly in adolescents and young adults 2, 1. Healthcare providers must monitor for:
- New or worsening depression, anxiety, or agitation
- Emergence of suicidal thoughts or behaviors
- Unusual changes in mood or behavior, especially during initial treatment or dose changes 1
Important Adverse Effects and Considerations
Paroxetine has a higher propensity for discontinuation syndrome compared to other SSRIs due to its shorter half-life 2:
- Symptoms include dizziness, sensory disturbances, anxiety, irritability, nausea, and "electric shock-like" sensations 1
- Requires gradual tapering over 10-14 days when discontinuing 2
Other significant concerns include:
- Serotonin syndrome risk, especially when combined with MAOIs or other serotonergic drugs 2, 1
- Increased bleeding risk when used with NSAIDs, aspirin, or warfarin 1
- QT prolongation concerns (though less than citalopram) 2
- Sexual dysfunction, nausea, somnolence, and weight gain 2, 4
- Greater anticholinergic effects than other SSRIs, causing more sedation and constipation 4
Drug Interactions
Paroxetine is both a substrate and inhibitor of cytochrome P450 2D6, creating significant interaction potential 2, 3:
- Contraindicated with MAOIs (must allow 2-week washout period) 1
- Contraindicated with thioridazine and pimozide due to cardiac risks 1
- Interacts with drugs metabolized by CYP2D6 including tamoxifen, metoprolol, and certain antipsychotics 2
- Can reduce conversion of tamoxifen to its active metabolite in breast cancer patients 2
Pharmacokinetics
- Well absorbed orally with extensive first-pass metabolism 3
- Elimination half-life of approximately 21 hours, consistent with once-daily dosing 3
- Steady-state achieved after 4-14 days 3
- Wide inter-individual variation in pharmacokinetics, with higher concentrations and slower elimination in elderly patients 3
- Reduced elimination in severe renal and hepatic impairment 3
Special Populations
In elderly patients (≥60 years), paroxetine requires dose adjustment 2:
- Start at lower doses (10 mg daily) due to altered pharmacokinetics 3
- Monitor closely for hyponatremia, which occurs more frequently in older adults 2
In pregnancy, paroxetine carries specific risks 1: