Side Effects of Paroxetine (Paxil)
Paroxetine (Paxil) has numerous side effects that can significantly impact quality of life, with approximately 63% of patients experiencing at least one adverse effect during treatment. The most common side effects of paroxetine include nausea, somnolence (sleepiness), sweating, decreased appetite, dizziness, sexual dysfunction, dry mouth, constipation, insomnia, and tremor. 1, 2
Common Side Effects
- Gastrointestinal effects: Nausea is the most common reason for discontinuation, along with dry mouth, constipation, and diarrhea 2
- Neurological effects: Somnolence (23% of patients), dizziness (13%), insomnia (13%), and tremor (8%) 2
- Sexual dysfunction: Ejaculatory disturbances (13%), decreased libido (3%), and other sexual problems are significantly more common with paroxetine than placebo 2
- Other common effects: Sweating, asthenia (weakness), anxiety, and headache 2
Serious Adverse Effects
- Serotonin syndrome: Characterized by mental status changes (agitation, confusion), autonomic hyperactivity (fever, tachycardia), and neuromuscular abnormalities (tremor, hyperreflexia). This can occur even at therapeutic doses, particularly in elderly patients 3, 1
- Discontinuation syndrome: Characterized by dizziness, fatigue, headache, nausea, sensory disturbances, anxiety, and irritability when paroxetine is stopped abruptly 1
- Bleeding risk: Increased risk of gastrointestinal bleeding, especially when combined with NSAIDs or antiplatelet medications 1
- QT prolongation: Can occur at higher doses, particularly in elderly patients 1
- Hyponatremia: Occurs in 0.5-12% of older adults, typically within the first month of treatment 1
Special Populations
Pregnancy
- Paroxetine is classified as pregnancy category D due to concerns about congenital cardiac malformations 1
- Third-trimester use has been linked to neonatal withdrawal symptoms including continuous crying, irritability, jitteriness, tremors, feeding difficulty, sleep disturbance, and in rare cases, seizures 1
- These neonatal symptoms typically appear within hours to days after birth and usually resolve within 1-4 weeks 1
Elderly Patients
- Higher risk of adverse effects due to altered pharmacokinetics 1
- Increased risk of cognitive impairment, hyponatremia, and falls 4
- Lower starting doses are recommended (10mg/day) 1
Breastfeeding
- Paroxetine is excreted in breast milk but at relatively low concentrations 1
- Considered one of the preferred SSRIs during breastfeeding due to minimal infant exposure 1
Drug Interactions
- Strong inhibitor of CYP2D6: Can increase levels of medications metabolized by this enzyme 4
- Contraindicated with MAOIs: Can cause severe, potentially fatal serotonin syndrome 1
- Tamoxifen: Paroxetine inhibits tamoxifen metabolism, potentially reducing its effectiveness in breast cancer treatment 4
- Other serotonergic medications: Increased risk of serotonin syndrome when combined with other drugs that increase serotonin levels 1, 2
Discontinuation Considerations
- Approximately 20% of patients discontinue paroxetine due to adverse effects in clinical trials 2
- Gradual tapering over 10-14 days is recommended to minimize withdrawal symptoms 1
- Paroxetine has a higher risk of discontinuation symptoms compared to other SSRIs due to its shorter half-life 1
Clinical Implications
- Paroxetine has more anticholinergic effects than other SSRIs 1
- Unlike benzodiazepines, paroxetine does not cause dependence and appears safer in overdose than tricyclic antidepressants 5
- Does not significantly impair psychomotor function or interact with alcohol at therapeutic doses 5
- Consider starting at lower doses (10mg/day) and titrating slowly, especially in elderly patients 1
When prescribing paroxetine, careful monitoring for side effects is essential, particularly during the initial weeks of treatment and when discontinuing the medication. The benefit-to-risk ratio should be carefully evaluated for each patient, with special caution in pregnant women, the elderly, and those on multiple medications.