PAXIL (Paroxetine) Indications
PAXIL is FDA-approved for treating major depressive disorder, obsessive-compulsive disorder, panic disorder, social anxiety disorder, generalized anxiety disorder, posttraumatic stress disorder, and premenstrual dysphoric disorder. 1
FDA-Approved Indications
According to the FDA drug label, PAXIL (paroxetine) is indicated for: 1
- Major Depressive Disorder (MDD) 2
- Obsessive-Compulsive Disorder (OCD) 2
- Panic Disorder 2
- Social Anxiety Disorder (Social Phobia) 2
- Generalized Anxiety Disorder (GAD) 2
- Posttraumatic Stress Disorder (PTSD) 2
- Premenstrual Dysphoric Disorder 2
Clinical Context and Evidence
Paroxetine is notably the only SSRI approved for all five anxiety disorders in addition to major depressive disorder, making it particularly valuable for patients with comorbid depression and anxiety. 3, 4
Efficacy Profile
Depression: Paroxetine 10-50 mg/day is significantly more effective than placebo and at least as effective as tricyclic antidepressants in 6-24 week trials for major depressive disorder. 3, 4
Anxiety Disorders: Paroxetine 20-60 mg/day demonstrates superior efficacy to placebo after 8-12 weeks of treatment across all approved anxiety disorders. 3, 4
OCD: Higher dosing strategies (up to 60 mg) show superior efficacy compared to lower doses for obsessive-compulsive disorder. 2
Panic Disorder: Paroxetine 10-60 mg/day significantly reduces panic attack frequency and maintains efficacy for up to 6 months, with faster onset of effect compared to clomipramine. 5
Important Safety Considerations
Black box warning: PAXIL carries an FDA black box warning for treatment-emergent suicidality, particularly in adolescents and young adults. 2, 1
Additional critical warnings include: 1
- Serotonin syndrome risk, especially when combined with MAOIs or other serotonergic drugs
- Discontinuation syndrome (paroxetine has higher risk than other SSRIs due to shorter half-life) 2
- Sexual dysfunction (paroxetine has higher rates than fluoxetine, fluvoxamine, nefazodone, or sertraline) 2
- Increased risk of nonfatal suicide attempts compared to placebo 2
Metabolism and Drug Interactions
Paroxetine is metabolized primarily through CYP2D6, which is subject to genetic polymorphism. 2 This has important implications:
- Paroxetine inhibits CYP2D6, potentially affecting metabolism of other drugs 2
- Genetic variation in CYP2D6 contributes to differential risk-to-benefit ratios among patients 2
- Caution needed when combining with drugs metabolized by CYP2D6 2
Clinical Practice Recommendations
The American College of Physicians recommends selecting second-generation antidepressants based on adverse effect profiles, cost, and patient preferences, as efficacy does not differ significantly among agents. 2 However, paroxetine's unique approval for the broadest range of anxiety disorders makes it a first-line option when treating comorbid depression and anxiety. 3, 4