What is the usage and dosage of Paroxetine (Selective Serotonin Reuptake Inhibitor) tablets?

Paroxetine Tablet: Usage and Dosage

Paroxetine is a potent selective serotonin reuptake inhibitor (SSRI) approved for major depressive disorder, obsessive-compulsive disorder, panic disorder, social anxiety disorder, generalized anxiety disorder, and post-traumatic stress disorder in adults, with typical dosing starting at 20 mg once daily and ranging up to 50-60 mg/day depending on indication. 1, 2, 3

Approved Indications and Dosing

Major Depressive Disorder

• Starting dose: 20 mg once daily 2, 3
• Therapeutic range: 20-50 mg/day 2, 3
• Treatment duration: 4-12 months after remission for first episode; prolonged treatment for recurrent depression 4

Anxiety Disorders (OCD, Panic Disorder, Social Anxiety Disorder, GAD, PTSD)

• Starting dose: 20 mg once daily 2, 3
• Therapeutic range: 20-60 mg/day 2, 3
• Maintenance: Continue for 24 weeks to 1 year to prevent relapse 2, 3

Dysthymia and Minor Depression

• Dosing: 10-40 mg/day 2, 3

Critical Pharmacokinetic Considerations

Nonlinear Kinetics

• Paroxetine exhibits nonlinear pharmacokinetics due to CYP2D6 enzyme saturation, causing disproportionate plasma concentration increases with dose escalation 4, 1
• Long-term use of 20 mg/day converts approximately 43% of normal metabolizers into functional poor metabolizers through auto-inhibition 4
• Steady-state levels achieved after 4-14 days with elimination half-life of 21 hours, supporting once-daily dosing 5

Genetic Variability

• CYP2D6 poor metabolizers may have plasma concentrations up to 7-fold higher than extensive metabolizers, requiring lower starting doses 4
• Consider genetic testing for CYP2D6 status before significant dose increases in patients with poor tolerance or unusual response 4

Dose Escalation Strategy

When Increasing Above 20 mg

• Dosage adjustment after the 20 mg starting dose should be guided by clinical effect, particularly when coadministered with enzyme inhibitors like cimetidine 1
• Monitor for emergence or worsening of adverse effects within 24-48 hours after dose increases 4
• Be particularly vigilant for serotonin syndrome symptoms (confusion, agitation, tremors, hyperreflexia, autonomic instability) 4

Common Pitfalls

• Higher doses are associated with increased dropout rates due to adverse effects, particularly during the first few weeks 4
• Higher doses carry increased risk of discontinuation syndrome compared to other SSRIs 4
• If poor tolerance occurs at doses above 20 mg, consider CYP2D6 genetic testing or switching to an alternative antidepressant 4

Special Population Dosing

Elderly Patients (≥60 years)

• Starting dose: 10 mg once daily 2, 3, 6
• Therapeutic range: 10-40 mg/day 2, 3, 6
• Higher plasma concentrations and slower elimination occur in elderly patients due to pharmacokinetic changes 5, 6
• Paroxetine may not be ideal for older adults due to anticholinergic effects 4

Renal and Hepatic Impairment

• Elimination is reduced in severe renal and hepatic impairment, requiring dose reduction 5, 6
• Initial dose should be reduced with subsequent adjustments guided by clinical effect 1

Drug Interactions Requiring Dose Adjustment

• Cimetidine increases paroxetine plasma concentrations by approximately 50%; adjust dose after 20 mg starting dose based on clinical effect 1
• Phenobarbital and phenytoin reduce paroxetine AUC by 25-50%; subsequent adjustments should be guided by clinical effect 1

Critical Drug Interactions

Contraindicated Combinations

• MAOIs (including linezolid and methylene blue): Absolute contraindication due to serotonin syndrome risk 1
• Pimozide: Contraindicated due to 151% increase in pimozide AUC and QT prolongation risk 1
• Thioridazine: Contraindicated 1

CYP2D6 Substrate Interactions

• Paroxetine significantly inhibits CYP2D6, saturating this enzyme early during dosing in >90% of patients 1
• Desipramine: Increases Cmax, AUC, and T½ by 2-, 5-, and 3-fold respectively 1
• Risperidone: Increases plasma concentrations approximately 4-fold 1
• Atomoxetine: Increases steady-state AUC by 6- to 8-fold and Cmax by 3- to 4-fold; initiate atomoxetine at reduced dose 1

Serotonergic Drug Cautions

• Exercise caution when coadministering with triptans, lithium, fentanyl, tramadol, or St. John's Wort due to serotonin syndrome risk 1
• Concomitant use with other SSRIs, SNRIs, or tryptophan is not recommended 1
• If triptan coadministration is necessary, observe patient carefully during initiation and dose increases 1

Bleeding Risk

• Warfarin: Pharmacodynamic interaction may increase bleeding risk despite unaltered prothrombin time; use with caution 1

Discontinuation Protocol

Tapering Strategy

• Gradual dose reduction over 10-14 days is recommended to limit withdrawal symptoms 4
• Paroxetine has the highest association with discontinuation syndrome among SSRIs 4, 7

Monitoring Requirements

Routine Monitoring

• Assess for activation symptoms (anxiety, agitation, insomnia, nervousness) within 24-48 hours of dose changes 4
• Use standardized symptom rating scales to objectively track response 8
• Monitor for serotonin syndrome after dose increases or when adding serotonergic medications 4

Cardiac Monitoring

• For patients with cardiac risk factors, consider ECG monitoring due to potential QT prolongation 4

Pediatric Considerations

• Paroxetine is NOT indicated for use in the pediatric population 7
• If used off-label, parental oversight is paramount with specific monitoring for suicidal ideation or behavioral activation 9

Adverse Effect Profile

Most Common Adverse Events

• Nausea, sexual dysfunction, somnolence, asthenia, headache, constipation, dizziness, sweating, tremor, and decreased appetite 2, 3, 7
• Paroxetine induces more sedation, constipation, sexual dysfunction, discontinuation syndrome, and weight gain compared to other SSRIs 7

Anticholinergic Effects

• Paroxetine is less activating but more anticholinergic than other SSRIs 4
• Has some affinity for muscarinic cholinergic receptors, though much less than tricyclic antidepressants 5

Pregnancy Considerations

• Paroxetine is categorized as Pregnancy Class D 7
• Recent data suggest increased rates of congenital malformations, though evidence is not conclusive 7

Comparative Efficacy

• Paroxetine is the most potent inhibitor of serotonin reuptake among currently available SSRIs 5, 7
• Efficacy is at least as effective as tricyclic antidepressants and comparable to other SSRIs for major depressive disorder 2, 3
• Paroxetine is the only SSRI approved for all five anxiety disorders plus major depressive disorder, making it particularly useful for comorbid depression and anxiety 2, 3