paroxetine

General Information

Paroxetine (Paxil) is an SSRI used across mood and anxiety disorders but notable for anticholinergic burden, weight gain, and discontinuation syndrome.

Potent CYP2D6 inhibition requires careful coordination with other psychotropics.

Compared with many SSRIs, paroxetine has a higher likelihood of discontinuation symptoms; gradual tapering and anticipatory counseling are central to safe switching.

The contrast view and the Paroxetine evidence feed can help balance anticholinergic load, discontinuation risk, and interaction profiles when considering regimen changes.

Perinatal planning matters: paroxetine has less favorable pregnancy data than some SSRIs, so alternatives are often preferred when feasible. When discontinuing, taper gradually to reduce discontinuation symptoms.

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Selective serotonin reuptake inhibition with mild norepinephrine reuptake inhibition at higher doses and notable muscarinic/histamine antagonism.

• SERT inhibitor with M1/H1 antagonism.

Metabolism and Pharmacokinetics

• Extensive hepatic metabolism via CYP2D6; nonlinear kinetics due to enzyme saturation; half-life ~21 h.
• Eliminated primarily in urine as metabolites.
• Older age and hepatic impairment can increase exposure; lower starting doses and slower titration help reduce anticholinergic adverse effects.

Dosing and Administration

• Start 20 mg once daily (morning); titrate by 10 mg weekly to 20–50 mg/day (IR).
• Controlled-release: start 25 mg daily; increase to 37.5–62.5 mg/day as needed.
• Taper by 10 mg every 1–2 weeks to mitigate discontinuation symptoms.
• When discontinuation symptoms occur despite tapering, slower dose reductions (smaller steps over longer intervals) are often better tolerated than abrupt pauses or rapid reductions.

Monitoring & Labs

• Suicidality and psychiatric activation during initiation and dose changes; align follow-up cadence with clinical risk.
• Weight and metabolic trends when appetite increases or weight gain becomes clinically meaningful; lifestyle supports are often introduced early.
• Discontinuation symptoms during tapering (dizziness, paresthesias, irritability); taper steps are often kept predictable to reduce abrupt stoppage.
• Sodium in older adults or diuretic users if symptoms suggest hyponatremia.
• Drug–drug interaction review at every visit due to potent CYP2D6 inhibition (TCAs, antipsychotics, tamoxifen).
• Anticholinergic adverse effects (constipation, urinary retention, cognitive clouding), especially in older adults and when other anticholinergics are on the medication list.

Paroxetine tends to be more discontinuation-prone than longer half-life SSRIs; plan tapering early rather than waiting until medication changes are urgent or time-sensitive overall.

Adverse Effects

Interactions

• Potent CYP2D6 inhibitor—adjust doses of TCAs, antipsychotics, tamoxifen, beta-blockers.
• Contraindicated with MAOIs; observe 14-day washout when switching.
• Additive serotonergic toxicity with triptans, SNRIs, linezolid, St. John’s wort.

Other Useful Information

• Baseline weight and metabolic labs are commonly tracked; alternatives may be preferred for patients at high metabolic risk.
• Anticholinergic effects can be more problematic in hepatic impairment and older adults; lower starting doses and slower titration are often used.
• When CYP2D6 substrates are part of a regimen (antipsychotics, TCAs, some beta-blockers), coordinate dosing and side-effect monitoring proactively to reduce sedation, orthostasis, or anticholinergic toxicity risk.

References

1. Paxil (paroxetine) prescribing information — DailyMed (2025)
2. APA Clinical Practice Guideline for the Treatment of Depression — American Psychiatric Association (2023)Guidelinedepressionclinical
3. CANMAT 2024 Clinical Guidelines for Major Depressive Disorder — Canadian Journal of Psychiatry (2024)