Paroxetine Classification and Mechanism
Paroxetine is a selective serotonin reuptake inhibitor (SSRI) antidepressant that works by blocking the reuptake of serotonin in the central nervous system. 1
Pharmacological Class
- Paroxetine belongs to the SSRI class of antidepressants, specifically a phenylpiperidine derivative. 2
- It is the most potent inhibitor of serotonin reuptake among all currently available SSRIs. 3, 2
- The drug demonstrates high selectivity for serotonin over norepinephrine, with minimal effects on dopamine reuptake. 1, 2
Mechanism of Action
- Paroxetine's therapeutic efficacy results from potentiation of serotonergic activity through inhibition of neuronal serotonin reuptake. 1
- The drug blocks serotonin uptake into human platelets in a concentration-dependent manner. 1
- Unlike tricyclic antidepressants, paroxetine has minimal affinity for muscarinic, alpha-adrenergic, dopaminergic, and histaminergic receptors, resulting in fewer anticholinergic and cardiovascular side effects. 1, 2
FDA-Approved Indications
- Major depressive disorder 3, 1
- Obsessive-compulsive disorder (OCD) 3, 1
- Panic disorder 3, 1
- Social anxiety disorder (social phobia) 3, 1
- Generalized anxiety disorder (GAD) 3, 1
- Posttraumatic stress disorder (PTSD) 3, 1
- Premenstrual dysphoric disorder 3
Key Pharmacokinetic Properties
- Paroxetine is completely absorbed after oral administration but undergoes extensive first-pass metabolism. 1
- The mean elimination half-life is approximately 21 hours, supporting once-daily dosing. 1, 2
- Steady-state concentrations are typically achieved within 10 days, though some patients may require longer. 1
- The drug is primarily metabolized by cytochrome P450 2D6 (CYP2D6) and also inhibits this enzyme, creating potential for drug-drug interactions. 3, 1, 2
Important Clinical Considerations
- Paroxetine carries a black box warning for treatment-emergent suicidality, particularly in adolescents and young adults. 3
- The American Academy of Child and Adolescent Psychiatry notes that paroxetine has been associated with increased risk of suicidal thinking or behavior compared to other SSRIs. 3
- Paroxetine is notably associated with discontinuation syndrome due to its shorter half-life, characterized by dizziness, sensory disturbances, anxiety, and flu-like symptoms. 3
- The drug interacts with medications metabolized by CYP2D6, requiring caution with concomitant use. 3