Paroxetine (Paxil): Uses, Dosage, Side Effects, and What to Expect

Paroxetine (brand name: Paxil / Paxil CR) is a selective serotonin reuptake inhibitor (ssri). Paroxetine is the most potent serotonin reuptake inhibitor among the SSRIs. It also has mild norepinephrine reuptake inhibition, significant anticholinergic activity (more than any other SSRI), and weak inhibition of nitric oxide synthase. These additional properties explain some of its unique characteristics: the anticholinergic activity contributes to sedation, dry mouth, constipation, and weight gain, while also making it the SSRI most likely to cause sexual dysfunction. Its short half-life (21 hours) and inhibition of its own metabolism make discontinuation particularly challenging.

• Major Depressive Disorder
• Generalized Anxiety Disorder
• Social Anxiety Disorder
• Panic Disorder
• Obsessive-Compulsive Disorder
• PTSD
• Premenstrual Dysphoric Disorder (Paxil CR)

Common off-label uses:

• Premature ejaculation (most effective SSRI for this)
• Hot flashes (Brisdelle — a branded low-dose formulation)
• Irritable bowel syndrome

Depression: start 20 mg/day, may increase by 10 mg/week to max 50 mg. Panic/social anxiety/GAD: start 20 mg, target 20-50 mg. OCD: start 20 mg, target 40-60 mg. Paxil CR: start 25 mg, max 62.5 mg. Take in the morning or evening; food reduces GI side effects. Elderly: start at 10 mg.

Initial effects in 1-2 weeks. Full antidepressant response in 4-6 weeks. OCD: 8-12 weeks.

• Sexual dysfunction (highest rate among SSRIs — up to 70%)
• Weight gain (most weight-gaining SSRI)
• Sedation and drowsiness
• Dry mouth
• Constipation
• Nausea
• Dizziness
• Sweating

• Severe discontinuation syndrome (worst among SSRIs due to short half-life and self-inhibiting metabolism)
• Suicidal ideation in young adults (black box warning)
• Serotonin syndrome
• Hyponatremia
• Increased bleeding risk
• Birth defects (cardiac malformations — FDA Category D, the only SSRI with Category D)

Strong CYP2D6 inhibitor — significantly increases levels of tamoxifen (reduces its efficacy — avoid combination), codeine, many antipsychotics, and tricyclic antidepressants. Contraindicated with MAOIs, pimozide, and thioridazine.

FDA Category D — the only SSRI in this category. Associated with increased risk of cardiac malformations (particularly atrial and ventricular septal defects) when used in the first trimester. PPHN risk with third-trimester use. Generally avoided during pregnancy; switch to sertraline or fluoxetine if antidepressant is needed.

The most difficult SSRI to discontinue. Its short half-life, lack of an active metabolite, and inhibition of its own metabolism (CYP2D6) create a steep drop in brain serotonin levels when doses are reduced. Discontinuation symptoms (brain zaps, dizziness, flu-like symptoms, irritability, electric shock sensations, vivid dreams) can be severe. Taper extremely gradually — 10% reductions every 2-4 weeks. Some patients require liquid formulation for precise micro-tapering over months.