Paroxetine

• Major Depressive Disorder
• Generalized Anxiety Disorder
• Panic Disorder
• Social Anxiety Disorder
• OCD
• PTSD

Paroxetine is a selective serotonin reuptake inhibitor (SSRI) antidepressant used to treat major depressive disorder, various anxiety disorders, and other psychiatric conditions. Known for its potent serotonin reuptake inhibition, it is also notable for having more anticholinergic activity than other SSRIs.

Mechanism of Action

Paroxetine works primarily by:

• Selectively inhibiting serotonin reuptake: Blocks the serotonin transporter (SERT) in presynaptic neurons
• Increasing synaptic serotonin: Enhanced serotonergic neurotransmission improves mood and reduces anxiety
• Mild anticholinergic activity: More than other SSRIs; contributes to some side effects
• Weak norepinephrine reuptake inhibition: Minor contribution to clinical effects

Therapeutic effects typically develop over 2-4 weeks as neuroplastic changes occur.

Available Formulations

Immediate-Release:

• Tablets: 10 mg, 20 mg, 30 mg, 40 mg
• Oral suspension: 10 mg/5 mL

Controlled-Release (Paxil CR):

• Tablets: 12.5 mg, 25 mg, 37.5 mg

Mesylate Salt (Pexeva):

• Tablets: 10 mg, 20 mg, 30 mg, 40 mg

Medical Uses

FDA-Approved Indications:

• Major depressive disorder (MDD)
• Generalized anxiety disorder (GAD)
• Panic disorder
• Social anxiety disorder (social phobia)
• Obsessive-compulsive disorder (OCD)
• Posttraumatic stress disorder (PTSD)
• Premenstrual dysphoric disorder (PMDD) - CR formulation

Dosing Guidelines

Major Depressive Disorder:

• IR: Start 20 mg daily; range 20-50 mg daily; max 50 mg
• CR: Start 25 mg daily; range 25-62.5 mg daily; max 62.5 mg

Panic Disorder:

• IR: Start 10 mg daily; target 40 mg daily; max 60 mg

OCD:

• IR: Start 20 mg daily; target 40 mg daily; max 60 mg

Social Anxiety/GAD:

• IR: 20 mg daily; max 60 mg (social anxiety), 50 mg (GAD)

PMDD (CR only):

• 12.5-25 mg daily throughout cycle or during luteal phase only

Important Safety Information

Black Box Warning:

• Increased risk of suicidal thinking and behavior in children, adolescents, and young adults (18-24 years) with major depressive disorder and other psychiatric disorders
• Monitor closely for clinical worsening and emergence of suicidal thoughts

Contraindications:

• Concurrent use of MAOIs (or within 14 days)
• Concurrent use of thioridazine
• Concurrent use of pimozide

Warnings and Precautions:

• Serotonin syndrome
• Discontinuation syndrome (paroxetine has highest incidence among SSRIs)
• Bleeding risk (especially with NSAIDs, aspirin, anticoagulants)
• Activation of mania/hypomania
• Hyponatremia (SIADH)
• Bone fracture risk
• Sexual dysfunction

Drug Interactions

CYP2D6 Inhibition (Strong):

• Paroxetine strongly inhibits CYP2D6
• Increases levels of: tamoxifen metabolites blocked, codeine activation blocked, many antipsychotics, beta-blockers, atomoxetine

Serotonergic Drugs:

• Risk of serotonin syndrome with triptans, tramadol, tryptophan, other antidepressants

Bleeding Risk:

• NSAIDs, aspirin, warfarin increase bleeding risk

MAOIs:

• Contraindicated; wait 14 days before or after MAOI use

Special Populations

• Hepatic Impairment: Start with lower doses; max 40 mg (IR)
• Renal Impairment: CrCl <30: Start 10 mg (IR); max 40 mg
• Elderly: Start 10 mg (IR) or 12.5 mg (CR); max 40 mg (IR)
• Pregnancy: Category D; associated with cardiac malformations and persistent pulmonary hypertension
• Lactation: Present in breast milk; generally considered acceptable but monitor infant
• Pediatric: Not approved for depression in children; increased suicidality risk