Paxil (Paroxetine)

  • Generic name: Paroxetine hydrochloride
  • Brand names: Paxil, Paxil CR (Controlled-Release); Seroxat, Seroxat CR
  • Drug class: Selective serotonin reuptake inhibitor (SSRI), Antidepressant

What is Paxil used for?

  • Depression
  • Panic disorder
  • Obsessive-compulsive disorder
  • Anxiety
  • Social phobia
  • Post-traumatic stress disorder
  • Premenstrual syndrome

Paxil CR vs Paroxetine

Paxil CR incorporates a multi-layer formulation called Geomatrix, which helps to slow dissolution and absorption. Regular paroxetine appears to reach steady state concentration at the same time, if not sooner than Paxil CR. Their half-lives are almost identical, with the CR actually having a shorter half-life than the regular (15-20 hours vs 21 hours)2.

Many people think that Paxil CR has a much longer half-life than in reality. Nevertheless the withdrawal symptoms of Paxil CR can be just as severe as of the regular paroxetine.

The main selling point of Paxil CR is improved tolerability, particularly less nausea. Generic paroxetine is significantly cheaper than Paxil CR.


  • Use with or within 14 days of MAO inhibitors
  • Concurrent use with thioridazine or pimozide

Drug interactions

Paroxetine is a very potent inhibitor of CYP2D6 and has greater potential for drug interactions than other SSRIs.

  • Antipsychotics (clozapine, haloperidol, risperidone, perphenazine): increased concentrations of antipsychotic medications.
  • Antiarrhythmic agents class Ic (encainide, flecainide, propafenone): possible inhibition of metabolism by paroxetine.
  • Metoprolol: severe hypotension possible.
  • NSAIDs (e.g. ibuprofen, naproxen): increased risk of bleeding. Concurrent use is not contraindicated but be aware of increased risk of bleeding, especially in persons with additional risk factors.
  • Pravastatin: increased blood glucose levels4.
  • Tricyclic antidepressants: increased peak plasma concentrations of TCA and increased sedation and anticholinergic symptoms. Use with caution.
  • Tramadol: risk of serotonin syndrome. Tramadol is metabolized by CYP2D6. So, concomitant use of tramadol with paroxetine may result in some inhibition of the tramadol metabolism, leading to decreased analgesic activity7. This combination should be used with great caution. Alternative analgesic may be preferable.

Paroxetine in combination with other medications

Trazodone is sometimes added to paroxetine to treat insomnia or resistant depression3. Talk to your doctor before using trazodone together with paroxetine, because this combination can produce severe serotonin syndrome.

Alprazolam (Xanax): no evidence for pharmacologic interactions between paroxetine and alprazolam5.

Clonazepam (Klonopin): drug interactions unlikely. Combined treatment with paroxetine and clonazepam provides more rapid onset of benefit for panic disorder6.


Paroxetine hcl has the highest rate and severity of withdrawal symptoms in comparison with other SSRIs, due to its shortest half-life of about 21 hours. Abrupt withdrawal results in rapid decrease of paroxetine levels in the brain which does not allow for brain adaptation. The drug has no active metabolites and leaves the body in 24 hours.

Paroxetine is very likely to cause pronounced withdrawal symptoms, and requires very gradual down-titration. Abrupt discontinuation can cause dizziness, abnormal dreams, and tingling sensations.

Further reading


  • 1. Paxil Prescribing Information PDF
  • 2. Paxil CR Prescribing Information PDF
  • 3. Fang Y, Yuan C, Xu Y, Chen J, Wu Z, Cao L, Yi Z, Hong W, Wang Y, Jiang K, Cui X, Calabrese JR, Gao K; OPERATION Study Team. A pilot study of the efficacy and safety of paroxetine augmented with risperidone, valproate, buspirone, trazodone, or thyroid hormone in adult Chinese patients with treatment-resistant major depression. J Clin Psychopharmacol. 2011 Oct;31(5):638-42
  • 4. Tatonetti NP, Denny JC, Murphy SN, Fernald GH, Krishnan G, Castro V, Yue P, Tsao PS, Kohane I, Roden DM, Altman RB. Detecting drug interactions from adverse-event reports: interaction between paroxetine and pravastatin increases blood glucose levels. Clin Pharmacol Ther. 2011 Jul;90(1):133-42 PubMed
  • 5. Calvo G, García-Gea C, Luque A, Morte A, Dal-Ré R, Barbanoj M. Lack of pharmacologic interaction between paroxetine and alprazolam at steady state in healthy volunteers. J Clin Psychopharmacol. 2004 Jun;24(3):268-76.
  • 6. Pollack MH, Simon NM, Worthington JJ, Doyle AL, Peters P, Toshkov F, Otto MW. Combined paroxetine and clonazepam treatment strategies compared to paroxetine monotherapy for panic disorder. J Psychopharmacol. 2003 Sep;17(3):276-82.
  • 7. Laugesen S, Enggaard TP, Pedersen RS, Sindrup SH, Brøsen K. Paroxetine, a cytochrome P450 2D6 inhibitor, diminishes the stereoselective O-demethylation and reduces the hypoalgesic effect of tramadol. Clin Pharmacol Ther. 2005 Apr;77(4):312-23.
  • 8. Wurst KE, Poole C, Ephross SA, Olshan AF. First trimester paroxetine use and the prevalence of congenital, specifically cardiac, defects: a meta-analysis of epidemiological studies. Birth Defects Res A Clin Mol Teratol. 2010 Mar;88(3):159-70. PubMed
  • 9. Begg EJ, Duffull SB, Saunders DA, Buttimore RC, Ilett KF, Hackett LP, Yapp P, Wilson DA. Paroxetine in human milk. Br J Clin Pharmacol. 1999 Aug;48(2):142-7. PubMed

Last updated: February, 2015

Advanced Consumer Info

paroxetine hcl

  • Pregnancy Category: D. Exposure to paroxetine in the first trimester of pregnancy may increase the risk for cardiac malformations8.
  • Breastfeeding: Paroxetine is considered "safe" during breast feeding because the dose transferred to the infant is quite below the recommended safety limit of 10% of the weight adjusted maternal dose and no adverse effects were reported9.
  • Elimination half-life: 21 hours
  • Mechanism of action: Paroxetine is a potent and selective inhibitor of the reuptake of serotonin (5-hydroxytryptamine). It exhibits some affinity for the muscarinic cholinergic receptors.
  • Paroxetine is more likely to cause sexual problems, weight gain, and withdrawal symptoms than the other SSRIs.