Paroxetine Side Effects
Paroxetine commonly causes nausea, sexual dysfunction, somnolence, dizziness, insomnia, tremor, sweating, and weight gain, with sexual dysfunction occurring at notably higher rates than other SSRIs. 1
Common Side Effects (≥5% incidence, at least twice placebo rates)
Based on FDA labeling data, the most frequently reported adverse effects include 1:
Gastrointestinal
- Nausea (most common reason for discontinuation)
- Dry mouth
- Constipation
- Diarrhea
- Decreased appetite
Neurological
- Somnolence (23% vs 9% placebo)
- Dizziness (13% vs 6% placebo)
- Insomnia (13% vs 6% placebo)
- Tremor (8% vs 2% placebo)
- Headache
Sexual Dysfunction (Gender-Specific)
- Ejaculatory disturbance in men (13% vs 0% placebo)
- Other male genital disorders (10% vs 0% placebo)
- Female genital disorders (anorgasmia, difficulty reaching orgasm)
- Decreased libido
Critical distinction: Paroxetine has higher rates of sexual dysfunction than fluoxetine, fluvoxamine, nefazodone, or sertraline 2
Other Common Effects
- Asthenia (weakness/fatigue)
- Sweating
- Nervousness/anxiety
Weight Gain
Paroxetine causes significantly more weight gain than sertraline, trazodone, or venlafaxine 2
Serious Adverse Events
Suicidality
SSRIs including paroxetine increase risk for nonfatal suicide attempts (OR 1.57, CI 0.99-2.55) compared to placebo, though not completed suicide 2. Monitor particularly in younger adults.
Rare but Important
- Serotonin syndrome (especially with MAOIs or other serotonergic drugs)
- Hyponatremia
- Seizures
- Cardiovascular effects (blood pressure/heart rate changes)
- QT prolongation in infants (maternal use)
- Hepatotoxicity (rare)
Drug Interactions
Paroxetine has the highest P450 2D6 inhibitory constant of all antidepressants 3. This creates significant interactions with:
- Tamoxifen (reduces efficacy, increases breast cancer mortality risk)
- Other 2D6 substrates
- 3A4 substrates
Discontinuation Rates
20% of patients discontinued paroxetine in major depression trials due to adverse events 1. Nausea and vomiting were the leading causes of discontinuation across all indications.
Overdose Presentation
Common overdose symptoms include somnolence, coma, nausea, tremor, tachycardia, confusion, vomiting, and dizziness. More serious manifestations: seizures (including status epilepticus), ventricular dysrhythmias, serotonin syndrome, rhabdomyolysis, and hepatic dysfunction 1.
Clinical Pitfalls
- Sexual dysfunction is likely underreported in clinical trials 2
- Behavioral activation/hyperactivity can occur, particularly in children <10 years 4
- Dose-dependent side effects mean starting at lower doses (7.5-20 mg) reduces adverse event burden 5
- Abrupt discontinuation causes withdrawal symptoms; taper gradually