Paroxetine: English spelling of the SSRI paroxetin
Paroxetine is the English spelling of the substance paroxetin. In English-language literature, international SmPCs and several brand names (Paxil in the USA, Seroxat in the EU) this form is used. In Germany the German spelling paroxetin is common. Pharmacologically, both refer to the same selective serotonin reuptake inhibitor (SSRI).
Paroxetine is among the most potent SSRIs but is also characterised by a comparatively pronounced discontinuation syndrome, strong CYP2D6 binding and a higher risk of weight gain. These properties influence clinical choice compared with sertraline, citalopram, escitalopram or fluoxetine.
Mechanism of action
Paroxetine selectively inhibits the serotonin reuptake transporter (SERT) on the presynaptic neuron. This raises serotonin concentration in the synaptic cleft, enhancing activation of postsynaptic serotonin receptors. The antidepressant and anxiolytic action results from adaptation of serotonergic circuits over several weeks.
Compared with other SSRIs, paroxetine additionally has:
- Weak anticholinergic effects via muscarinic receptors, which can contribute to dry mouth, constipation and sexual dysfunction
- Weak inhibition of the noradrenaline reuptake transporter (NET) at higher doses
- Very strong CYP2D6 inhibition, leading to clinically relevant interactions
Paroxetine is metabolised hepatically, with non-linear pharmacokinetics on dose escalation. Plasma half-life is about 21 hours, so once-daily dosing is sufficient.
Indications
- Major depression: acute and maintenance therapy
- Generalised anxiety disorder (GAD)
- Panic disorder with or without agoraphobia
- Social phobia: paroxetine is among the best-studied SSRIs in this indication
- Post-traumatic stress disorder (PTSD)
- Obsessive-compulsive disorder (OCD): often higher doses required
- Premenstrual dysphoric disorder (PMDD): off-label or specifically approved
- Vasomotor symptoms in menopause: low-dose paroxetine (Brisdelle in the USA)
Dosing and administration
Major depression and GAD: starting dose 20 mg in the morning, titration to 20 to 50 mg per day.
Panic disorder: start with 10 mg, slow titration to 20 to 40 mg.
Social phobia: 20 to 50 mg per day.
OCD: 20 to 60 mg per day, often at the upper end.
Vasomotor symptoms: 7.5 mg in the evening.
Take regardless of meals. Careful titration reduces initial gastrointestinal complaints and sleep disturbances.
Slow tapering: reduce dose stepwise over several weeks when stopping, to minimise withdrawal symptoms.
Side effects
Very common: nausea, sexual dysfunction (loss of libido, anorgasmia, erectile dysfunction), sleep disturbance, dizziness, dry mouth, sweating, tremor.
Common: weight gain, fatigue, constipation, diarrhoea, visual disturbance, yawning, asthenia, akathisia, abnormal dreams.
Uncommon: hyponatraemia (especially in older patients), raised liver values, pruritus, allergic skin reactions, tachycardia, syncope.
Rare and very rare: serotonin syndrome, Stevens Johnson syndrome, anaphylaxis, hepatitis, pancreatitis, suicidal thoughts (especially at therapy start and in younger patients), bone fractures.
Discontinuation syndrome:
- With abrupt or too rapid tapering: dizziness, paraesthesia (electric shock-like), nausea, sleep disturbance, irritability, flu-like symptoms, sensory phenomena
- Onset usually 1 to 3 days after the last dose, duration 2 to 4 weeks, longer in some cases
- Prophylaxis: slow tapering over weeks to months
- Among SSRIs, paroxetine has the most pronounced discontinuation syndrome
Interactions
- MAO inhibitors (tranylcypromine, moclobemide): risk of serotonin syndrome, combination contraindicated; minimum 14-day interval
- Linezolid, methylene blue: also risk of serotonin syndrome
- Other serotonergic substances (SNRIs, triptans, tramadol, pethidine, lithium, St John's wort): additive effect, often clinically tolerable, but counsel about warning signs
- CYP2D6 substrates (metoprolol, codeine, tamoxifen, tricyclics): level changes; especially caution with tamoxifen as efficacy may be diminished
- NSAIDs and anticoagulants: increased bleeding risk through SSRI-related platelet inhibition
- Cimetidine: raised paroxetine levels
- Phenytoin, phenobarbital, carbamazepine: level fall
Special considerations
Pregnancy: paroxetine shows a slightly increased risk of congenital heart defects compared with other SSRIs (mainly first trimester) and neonatal adaptation problems. If an SSRI is needed in pregnancy, sertraline or fluoxetine are usually preferred.
Breastfeeding: paroxetine passes in small amounts into milk; breastfeeding is possible after individual assessment. Watch the infant for poor feeding or irritability.
Children and adolescents: increased risk of suicidal thoughts and behaviour, use only on strict indication and with child psychiatry support.
Older patients: increased sensitivity, risk of hyponatraemia and fractures. Low starting doses, careful titration.
Tamoxifen: paroxetine can reduce activation of tamoxifen to its active metabolite endoxifen, with theoretically lower antitumour activity. In breast cancer patients, prefer alternatives such as venlafaxine or citalopram.
Driving: caution in the first weeks or with dose changes, since dizziness, concentration problems or drowsiness can occur.
Patient communication: realistic expectation of effect (4 to 6 weeks for full effect), counselling about side effects and discontinuation, shared decision-making increases adherence and confidence in therapy.
Related substances
- Paroxetin, German spelling of the same substance
- Agomelatine, melatonergic antidepressant
- Desvenlafaxine, SNRI antidepressant
- Buspirone, anxiolytic for augmentation
- Bupropion, NDRI in depression with reduced drive
Frequently asked questions
Paroxetine or paroxetin?
Paroxetine is the English spelling, paroxetin the German. Both refer to the same SSRI substance.
Why does paroxetine cause particular problems on stopping?
Paroxetine has a relatively short half-life and no active long-acting metabolites. On stopping, levels fall rapidly, which can trigger withdrawal symptoms. Substances with long half-life like fluoxetine are more favourable in this regard. A slow taper over weeks to months markedly reduces complaints.
Why is paroxetine problematic with tamoxifen?
Paroxetine is a strong CYP2D6 inhibitor. Tamoxifen is converted to its active metabolite endoxifen via CYP2D6. Inhibition therefore reduces antitumour effect. In women with breast cancer, paroxetine should be avoided and switched to alternatives such as venlafaxine or citalopram.
How quickly does paroxetine work?
Initial effects on sleep and drive can be noticed after 1 to 2 weeks, the full antidepressant effect develops over 4 to 6 weeks. In anxiety disorders improvement can take longer. Patience and consistent intake are important.
Sources
- EMA European Medicines Agency
- BfArM Federal Institute for Drugs and Medical Devices
- AWMF guideline depression and anxiety disorders
- Gelbe Liste paroxetin monograph
Legal notice and disclaimer
The information on this page is provided for general information purposes only and does not constitute medical advice, diagnosis or treatment recommendation. It does not replace the advice of a licensed physician or pharmacist. Medicines should only be used after a doctor's prescription or pharmacy supply. All information is based on summaries of product characteristics and accepted scientific sources at the time of writing; the current SmPC of the manufacturer is always decisive. Sanoliste accepts no liability for completeness, timeliness or accuracy. In a medical emergency, dial the emergency number 112.