What are the recommended doses of paroxetine (selective serotonin reuptake inhibitor) for adults with depression or anxiety, considering factors such as history of suicidal thoughts, bipolar disorder, and impaired renal function?

Paroxetine Dosing for Depression and Anxiety Disorders in Adults

Standard Dosing by Indication

For major depressive disorder, start paroxetine at 20 mg once daily in the morning, with dose increases of 10 mg at weekly intervals up to a maximum of 50 mg/day for non-responders. 1

Major Depressive Disorder

• Initial dose: 20 mg/day as a single morning dose 1
• For patients not responding to 20 mg, increase in 10 mg increments at intervals of at least 1 week 1
• Maximum dose: 50 mg/day 1
• Maintenance dosing averages approximately 30 mg/day for sustained efficacy up to 1 year 1
• The 20 mg starting dose represents both the minimal effective dose and the optimal dose for most patients 2

Obsessive-Compulsive Disorder (OCD)

• Target dose: 40 mg/day 1
• Start at 20 mg/day, then increase in 10 mg increments at weekly intervals 1
• Dosing range in clinical trials: 20-60 mg/day 1
• Maximum dose: 60 mg/day 1
• Higher doses (60 mg) demonstrate superior efficacy compared to lower doses for OCD 3

Panic Disorder

• Target dose: 40 mg/day 1
• Start at 10 mg/day (lower than depression dosing) 1
• Increase in 10 mg increments at weekly intervals 1
• Dosing range: 10-60 mg/day 1
• Maximum dose: 60 mg/day 1

Social Anxiety Disorder

• Recommended dose: 20 mg/day 1
• This is both the initial and recommended maintenance dose 1
• Clinical trials used 20-60 mg/day, but available evidence does not suggest additional benefit above 20 mg/day 1
• Maximum evaluated dose: 60 mg/day 1

Generalized Anxiety Disorder (GAD) and Post-Traumatic Stress Disorder (PTSD)

• Effective dosing range: 20-60 mg/day 4, 5
• Paroxetine is the only SSRI approved for GAD and all five anxiety disorders 4, 5

Special Population Considerations

Elderly Patients (≥60 years)

• Therapeutic dose range: 20-40 mg/day 2
• Start at lower doses due to higher plasma concentrations and slower elimination in elderly patients 6
• Elderly patients have prolonged elimination half-life compared to younger adults 7
• Serious adverse events are extremely rare even in this population 6

Renal Impairment

• Severe renal impairment requires dose reduction due to prolonged elimination half-life and increased plasma concentrations 7
• Start at lower doses and titrate cautiously 7

Hepatic Impairment

• Reduce dose in hepatic impairment due to increased plasma concentrations and prolonged elimination 7

CYP2D6 Poor Metabolizers

• CYP2D6 poor metabolizers are at significantly higher risk of toxicity with elevated paroxetine blood levels 3
• Paroxetine is metabolized through CYP2D6, which is subject to genetic polymorphism 3, 7
• Consider genetic testing if unexpected adverse effects occur at standard doses 3
• Poor metabolizers have nonlinear pharmacokinetics with dose escalation 7

Critical Safety Considerations

Bipolar Disorder

• Never use paroxetine monotherapy in bipolar disorder 8
• Always combine with a mood stabilizer to prevent mood destabilization or manic episodes 8
• The only FDA-approved combination for bipolar depression is olanzapine/fluoxetine, not paroxetine 8

Suicidality Warning

• Black box warning for treatment-emergent suicidality, particularly in adolescents and young adults 3
• Close monitoring is essential, especially during initial treatment and dose changes 3

Drug Interactions

• Paroxetine inhibits CYP2D6, creating significant drug-drug interaction risks 3
• Caution with other CYP2D6 substrates including venlafaxine and other medications metabolized through this pathway 3

Administration Guidelines

Timing and Food

• Administer as a single daily dose, usually in the morning 1
• Can be taken with or without food 1

Dose Adjustment Intervals

• Minimum interval between dose changes: 1 week 1, 2
• Steady-state concentrations are reached after 7-14 days 7
• Terminal elimination half-life is approximately 24 hours 7

Duration of Treatment

• Acute episodes of major depressive disorder require several months or longer of sustained therapy 1
• Maintenance therapy efficacy is demonstrated for up to 1 year 1
• For anxiety disorders, improvement is maintained for 24 weeks to 1 year 4, 5
• Periodically reassess patients to determine need for continued treatment 1

Common Adverse Effects

The most common adverse events include nausea, sexual dysfunction, somnolence, asthenia, headache, constipation, dizziness, sweating, tremor, and decreased appetite 4, 5. Paroxetine is generally better tolerated than tricyclic antidepressants and has a tolerability profile similar to other SSRIs 4, 5.