What are the side effects of Paxil (paroxetine)?

Side Effects of Paxil (Paroxetine)

Paxil causes side effects in approximately 63% of patients, with the most common being nausea, sexual dysfunction, somnolence, sweating, and dizziness, while serious risks include serotonin syndrome, discontinuation syndrome, increased bleeding risk, and cardiac congenital malformations in pregnancy. 1

Common Side Effects (Occurring in ≥5% of Patients)

The most frequently reported adverse effects that occur at least twice as often as placebo include: 2

Gastrointestinal Effects:

• Nausea (most common, reported in up to 26% of patients) 2
• Dry mouth 2
• Constipation 2
• Decreased appetite 1, 2
• Diarrhea 2

Neurological Effects:

• Somnolence (23% vs 9% placebo) 2
• Dizziness (13% vs 6% placebo) 2
• Insomnia (13% vs 6% placebo) 2
• Tremor (8% vs 2% placebo) 1, 2

Sexual Dysfunction (Gender-Specific):

• Ejaculatory disturbance in males (13% vs 0% placebo) 2
• Other male genital disorders including impotence (10% vs 0% placebo) 2
• Female genital disorders including anorgasmia (2% vs 0% placebo) 2
• Decreased libido (3% vs 0% placebo) 1, 2

Other Common Effects:

• Sweating 1, 2
• Asthenia (weakness) 1, 2
• Nervousness 2

Serious Adverse Effects Requiring Immediate Attention

Serotonin Syndrome:

• Can occur even at therapeutic doses, particularly in elderly patients 1
• Characterized by mental status changes, autonomic hyperactivity (fever, tachycardia), and neuromuscular abnormalities (tremor, rigidity, myoclonus) 1
• Risk dramatically increases when combined with MAOIs or other serotonergic drugs 1, 2

Cardiovascular Risks:

• Increased gastrointestinal bleeding risk, especially when combined with NSAIDs, aspirin, or antiplatelet medications 1, 2
• QT prolongation can occur at higher doses, particularly in elderly patients 1

Metabolic Effects:

• Hyponatremia occurs in 0.5-12% of older adults, typically within the first month of treatment 1

Discontinuation Syndrome

Paroxetine has the highest risk of discontinuation symptoms among all SSRIs due to its shorter half-life. 1

Withdrawal symptoms include: 1

• Dizziness
• Fatigue and headache
• Nausea
• Sensory disturbances (electric shock sensations)
• Anxiety and irritability

Critical Management: Gradual tapering over 10-14 days is essential to minimize withdrawal symptoms 1. Abrupt discontinuation should be avoided unless severe allergic reaction occurs 2.

Special Population Considerations

Pregnancy - Category D

Paroxetine poses significant fetal risks and should be avoided in pregnancy when possible: 1, 2

• Increased risk of congenital cardiac malformations 1, 2
• Third-trimester use linked to neonatal withdrawal symptoms including continuous crying, irritability, jitteriness, tremors, feeding difficulty, sleep disturbance, and rarely seizures 1
• Neonatal symptoms typically appear within hours to days after birth and resolve within 1-4 weeks 1
• Risk of persistent pulmonary hypertension in newborns 2

Elderly Patients

Elderly patients require special dosing considerations: 1

• Higher risk of adverse effects due to altered pharmacokinetics 1
• Start at 10mg/day (half the standard dose) and titrate slowly 1
• Increased risk of hyponatremia 1
• Greater susceptibility to serotonin syndrome 1

Breastfeeding

• Paroxetine is excreted in breast milk at relatively low concentrations 1
• Considered one of the preferred SSRIs during breastfeeding due to minimal infant exposure 1

Discontinuation Rates Due to Side Effects

20% of patients discontinued paroxetine in clinical trials for major depression due to adverse events (compared to lower rates for other conditions: 16.1% social anxiety disorder, 11.8% OCD, 9.4% panic disorder). 2

The most common side effects leading to discontinuation (≥1% and at least twice placebo rate) were: 2

• Nausea (3.2% vs 1.1% placebo)
• Somnolence (2.3% vs 0.7% placebo)
• Asthenia (1.6% vs 0.4% placebo)
• Abnormal ejaculation (1.6% vs 0% placebo)

Important Drug Interactions

Absolute Contraindications: 1, 2

• MAOIs (risk of fatal serotonin syndrome) - must wait appropriate washout period 1, 2

Significant Interactions Requiring Monitoring: 2

• Warfarin, aspirin, NSAIDs (increased bleeding risk)
• Tamoxifen (paroxetine inhibits conversion to active metabolite)
• Drugs metabolized by CYP2D6 (tricyclic antidepressants, metoprolol, etc.)
• Other serotonergic drugs (triptans, tramadol, St. John's wort, lithium)
• Pimozide (cardiac effects)

Unique Characteristics Compared to Other SSRIs

Paroxetine has more anticholinergic effects than other SSRIs 1, which explains higher rates of:

• Dry mouth
• Constipation
• Urinary hesitancy (3% vs 1% placebo) 2

Paroxetine is the most potent inhibitor of CYP2D6 among antidepressants, leading to more drug-drug interactions than other SSRIs. 3

Clinical Pitfalls to Avoid

1. Never stop abruptly - always taper gradually over 10-14 days minimum 1
2. Screen for MAOI use before initiating therapy 1, 2
3. Avoid in pregnancy unless benefits clearly outweigh risks; consider alternative SSRIs 1, 2
4. Reduce starting dose by 50% in elderly patients (start 10mg instead of 20mg) 1
5. Monitor for bleeding when combined with anticoagulants or antiplatelet agents 1, 2
6. Counsel patients about sexual side effects before starting treatment, as these occur in >10% of patients 2