Is paroxetine (selective serotonin reuptake inhibitor) used to treat anxiety?

Paroxetine for Anxiety

Yes, paroxetine is FDA-approved and highly effective for treating multiple anxiety disorders, including panic disorder, social anxiety disorder, generalized anxiety disorder, and post-traumatic stress disorder. 1

FDA-Approved Anxiety Indications

Paroxetine has the broadest FDA approval among SSRIs for anxiety disorders 2:

• Panic disorder (with or without agoraphobia) 1
• Social anxiety disorder (social phobia) 1
• Generalized anxiety disorder 1
• Post-traumatic stress disorder 1
• Obsessive-compulsive disorder 1

Notably, paroxetine is the only SSRI currently approved for both social anxiety disorder and generalized anxiety disorder, making it the only drug in its class indicated for all five major anxiety disorders. 3

Clinical Efficacy Evidence

Panic Disorder

In three 10-12 week placebo-controlled trials, paroxetine (10-60 mg/day) demonstrated significant superiority over placebo 1:

• 76% of patients on paroxetine 40 mg/day were panic attack-free at endpoint versus 44% on placebo 1
• Mean effective dose at completion was approximately 40 mg/day 1
• Long-term data show paroxetine significantly reduces relapse risk over 3 months compared to placebo 1

Social Anxiety Disorder

Three 12-week multicenter trials established efficacy 1:

• 69-77% of paroxetine-treated patients were CGI responders versus 29-42% on placebo 1
• Paroxetine 20 mg/day showed significant superiority; higher doses (40-60 mg) showed no additional benefit 1
• Efficacy maintained for 24 weeks to 1 year 2

Generalized Anxiety Disorder

Paroxetine demonstrated significant improvements in anxiety symptoms and global function compared to placebo 1:

• Similar efficacy to imipramine but greater efficacy than benzodiazepines 3
• Improvement maintained for up to 1 year 3

Obsessive-Compulsive Disorder

Two 12-week trials showed dose-dependent efficacy 1:

• Paroxetine 40-60 mg/day produced 6-7 point reductions on YBOCS versus 3-4 points with placebo 1
• Long-term extension data demonstrate sustained response and relapse prevention over 6 months 1

Mechanism and Pharmacology

Paroxetine is the most potent inhibitor of serotonin reuptake among all available SSRIs 4, 5:

• Selectively blocks presynaptic serotonin reuptake with minimal effects on norepinephrine or dopamine 1
• Elimination half-life of approximately 21 hours supports once-daily dosing 1
• Steady-state concentrations achieved after 7-14 days 1

Dosing Considerations

Start with 20 mg/day for most anxiety disorders; may increase to 40-60 mg/day as needed 1:

• Social anxiety disorder: 20 mg/day is typically sufficient 1
• Panic disorder: Mean effective dose ~40 mg/day 1
• OCD: Higher doses (40-60 mg/day) may be required 1
• Increase dose gradually in 10 mg increments at weekly intervals if needed 1

Pediatric Considerations

For children and adolescents (ages 6-18) with anxiety disorders, the American Academy of Child and Adolescent Psychiatry guidelines recommend 2:

• SSRIs as a class (including paroxetine) are more effective than placebo for social anxiety, generalized anxiety, separation anxiety, and panic disorder 2
• However, paroxetine has been associated with increased risk of suicidal thinking or behavior compared to other SSRIs 2
• Combination treatment (CBT plus SSRI) is preferred over monotherapy when feasible 2

Critical Safety Warnings

Discontinuation Syndrome

Paroxetine has the highest risk of discontinuation syndrome among SSRIs 2:

• Characterized by dizziness, nausea, paresthesias, anxiety, insomnia, and flu-like symptoms 2
• Occurs with missed doses or abrupt discontinuation 2
• Taper slowly when discontinuing to minimize withdrawal symptoms 2

Drug Interactions

Paroxetine interacts with drugs metabolized by CYP2D6 2:

• Contraindicated with MAOIs due to serotonin syndrome risk 2
• Exercise caution when combining with other serotonergic drugs 2
• May reduce effectiveness of tamoxifen by inhibiting conversion to active metabolite 2

Suicidality Risk

Black box warning for treatment-emergent suicidality, particularly in adolescents and young adults 2:

• Monitor closely during initial weeks of treatment and after dose changes 2
• Paroxetine shows higher suicidality risk compared to other SSRIs 2

Common Adverse Effects

Most frequent adverse events (≥5% and twice placebo rate) across anxiety disorders 1:

• Nausea, dry mouth, constipation, decreased appetite 1
• Somnolence, dizziness, tremor 1
• Sweating, asthenia 1
• Sexual dysfunction (abnormal ejaculation, impotence, decreased libido) 1

Sexual dysfunction and sweating are particularly common with paroxetine compared to other SSRIs 1, 5.

Comparative Advantages

Paroxetine is the preferred SSRI when treating patients with comorbid depression and multiple anxiety disorders 3:

• Only SSRI approved for all five major anxiety disorders plus depression 3
• High degree of psychiatric comorbidity between depression and anxiety makes broad-spectrum coverage advantageous 3
• Generally better tolerated than tricyclic antidepressants with lower anticholinergic burden 3, 4

Clinical Pitfalls to Avoid

1. Do not use paroxetine as first-line in adolescents given higher suicidality risk compared to other SSRIs like fluoxetine 2
2. Never abruptly discontinue due to severe withdrawal syndrome risk 2
3. Avoid in patients taking tamoxifen for breast cancer due to CYP2D6 inhibition 2
4. Screen for bipolar disorder before initiating, as SSRIs can precipitate mania 2
5. Monitor blood pressure as paroxetine can cause sustained hypertension in some patients 2