Side Effects of Paroxetine CR 12.5mg
Paroxetine CR 12.5mg commonly causes nausea, headache, somnolence, dry mouth, sexual dysfunction, sweating, and insomnia, with nausea being the most frequent reason for discontinuation in clinical trials. 1
Most Common Side Effects (≥5% incidence)
Based on FDA-approved labeling, the following side effects occur at rates at least twice that of placebo in patients taking paroxetine CR 12.5-50mg daily: 1
Gastrointestinal Effects
- Nausea is the most prominent side effect, occurring in 3.2-4.0% of patients (leading to discontinuation) and is the most common reason patients stop the medication 1
- Dry mouth, constipation, and diarrhea occur frequently 1
- These gastrointestinal effects are characteristic of all SSRIs due to increased serotonergic activity in the gut 2
Central Nervous System Effects
- Somnolence (23% vs 9% placebo) is very common and may be dose-dependent 1
- Dizziness (13% vs 6% placebo), insomnia (13% vs 6% placebo), and tremor (8% vs 2% placebo) occur frequently 1
- Nervousness, anxiety, and confusion can occur, though less commonly 1
Sexual Dysfunction
- Sexual side effects are particularly prominent with paroxetine compared to other SSRIs 3
- In males: ejaculatory disturbance/delay (13% vs 0% placebo), erectile difficulties, and impotence (10% vs 0% placebo) 1
- In females: anorgasmia and difficulty reaching climax/orgasm (2% vs 0% placebo) 1
- Decreased libido occurs in 3% of patients 1
Other Common Effects
- Sweating occurs frequently and is a common reason for discontinuation 1
- Asthenia (weakness/fatigue) affects 1.6% of patients sufficiently to cause discontinuation 1
- Weight gain is more common with paroxetine than with sertraline, trazodone, or venlafaxine 3
Serious Adverse Events
Suicidality Risk
- SSRIs including paroxetine are associated with increased risk of nonfatal suicide attempts (odds ratio 1.57-2.25) compared to placebo, though not completed suicide 3
- This risk requires monitoring, particularly in younger patients and those with mental health conditions 3
Discontinuation Syndrome
- Paroxetine has a relatively short half-life (approximately 21-24 hours) which increases the risk of withdrawal symptoms if stopped abruptly 2, 4
- Gradual dose tapering is essential to minimize discontinuation effects 2
Drug Interactions
- Paroxetine is the most potent inhibitor of cytochrome P450 2D6 among all antidepressants (Ki = 0.065-4.65 micromoles) 5
- This creates significant potential for drug interactions with other medications metabolized by 2D6, including tricyclic antidepressants, certain beta-blockers, and tamoxifen 5
- Paroxetine also inhibits CYP3A4, creating additional interaction potential 5
Cardiovascular Effects
- Unlike tricyclic antidepressants, paroxetine does not cause significant cardiac conduction disturbances or cardiovascular effects at therapeutic doses 4
- However, monitoring is still warranted in patients with pre-existing cardiac conditions 4
Special Populations
Elderly Patients
- Higher plasma concentrations and slower elimination occur in elderly patients due to age-related changes in drug metabolism 2
- Starting at lower doses (potentially 10mg or less) is prudent in this population 2
- Cognitive impairment has been reported in elderly patients taking paroxetine 5
Patients with Renal or Hepatic Impairment
- Elimination is reduced in severe renal and hepatic impairment, requiring dose adjustment 2
- Despite altered pharmacokinetics, serious adverse events remain extremely rare even in overdose 2
Clinical Considerations
Tolerability Profile
- Paroxetine has minimal anticholinergic effects compared to tricyclic antidepressants, though it does have weak affinity for muscarinic receptors 2, 4
- The drug does not significantly impair psychomotor function at doses of 20-30mg 6
- Overall withdrawal rates due to adverse effects are lower than with tricyclic antidepressants 4