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Paroxetine (Paxil) belongs to a class of antidepressant agents known as selective serotonin-reuptake inhibitors (SSRIs). It also has sedative and motor-impairing properties, as well as amnestic, anticonvulsant, and skeletal muscle relaxant effects, and can also be used to treat hot flashes associated with menopause. It is very important not to take any MAOI (monoamino oxidase inhibitors) during or within 14 days of taking an SSRI due to the posibility of a dangerous drug interaction.

Introduction to Paroxetine


Using Paroxetine

Ways of Administration

Effects of Paroxetine

Pharmacology of Paroxetine

LD50 (mg/kg) (hydrochloride hemihydrate) :
Mice : 500 orally, 845 subcutaneously

Chemistry of Paroxetine

Column 1 Column 2
Systematic(IUPAC) name: (3S,4R)-3-[(1,3-Benzodioxol-5-yloxy)methyl]-4-(4-fluorophenyl)piperidine
Synonyms: (-)-trans-4-(p-fluorophenyl)-3-[[3,4-(methylendioxy)phenoxy]methyl]piperidine, FG-7051, BRL-29060; Aropax, Deroxat, ParoLich, Paroxat, Paxil, Sereupin, Seroxat, Tagonis (hydrochloride hemihydrate); Pexeva, Paroxetine mesylate, Divarius, Euplix (methanesulfonate)
Molecular Formula: C19H20FNO3
Molar mass: 329.37 g/mol, 374.94 g/mol (hydrochloride hemihydrate), 425.47 g/mol (methanesulfonate)
CAS Registry Number: 61869-08-7, 110429-35-1 (hydrochloride hemihydrate), 78246-49-8 (hydrochloride), 64006-44-6 (maleate), 217797-14-3 (methanesulfonate)
Melting Point: 129-131 °C (hydrochloride hemihydrate), 136-138°C (maleate), 147-150°C (methanesulfonate)
Boiling Point: no data
Flash Point: no data
Solubility: Hydrochloride hemihydrate 5.4 mg/mL in water; Methanesulfonate > 1 g/mL in water
Additionnal data: none
Notes: Maleate crystals from ethanol-ether; methanesulfonate aspect odorless off-white powder

The Dangers of Paroxetine

It shares the common side effects and contraindications of other SSRIs, with high rates of nausea, somnolence, and sexual side effects. Paroxetine is also associated with clinically significant weight gain. This drug should not be used on pediatric patients, as it remains ineffective and possibly dangerous to children.

The development of a potentially life-threatening serotonin syndrome or Neuroleptic Malignant Syndrome (NMS)-like reactions have been reported with SNRIs and SSRIs alone, including treatment with PAXIL, but particularly with concomitant use of serotonergic drugs (including triptans) with drugs that impair metabolism of serotonin (including MAOIs), or with antipsychotics or other dopamine antagonists.

Cases of akathisia and activation syndrome have been observed during paroxetine treatment.

Paroxetine and other SSRIs have been shown to cause sexual side effects in most patients, both males and females. In males, paroxetine is also linked to sperm DNA fragmentation.

Discontinuation/Withdrawal Syndrome

Discontinuing paroxetine is associated with a high risk of withdrawal syndrome. GlaxoSmithKline was forced to admit that paroxetine can cause severe withdrawal symptoms when stopped. In 2001, the WHO ranked paroxetine as one of the most difficult antidepressants to withdraw from.

The FDA published a new product warning about the drug, and in the same week the International Federation of Pharmaceutical Manufacturers Associations declared the company guilty of misleading the public about paroxetine [being easily discontinued].

A well-described discontinuation syndrome occurs with the selective serotonin reuptake inhibitors, common symptoms including dizziness, headache, nausea and lethargy. Rare antidepressant discontinuation syndromes include extrapyramidal syndromes and mania/hypomania. Common withdrawal symptoms for paroxetine include nausea, dizziness, lightheadedness and vertigo; insomnia, nightmares and vivid dreams; feelings of electricity in the body, as well as crying and anxiety.

All these syndromes, even isolated discontinuation symptoms, share three common features that facilitate diagnosis; abrupt onset within days of stopping the antidepressant, a short duration when untreated and rapid resolution when the antidepressant is reinstated.

Strategies for the prevention and management of such symptoms include warning patients about the possibility of discontinuation symptoms, encouraging good antidepressant adherence and tapering antidepressants at the end of treatment.

Side Effects

Among the common adverse effects associated with paroxetine treatment of depression and listed in the prescribing information, those with the greatest difference from placebo are nausea (26% on paroxetine vs 9% on placebo), somnolence (23% vs. 9% on placebo), ejaculatory disturbance (13% vs. 0% on placebo), other male genital disorders (10% vs. 0% on placebo), asthenia (15% vs. 6% on placebo), sweating (11% vs. 2% on placebo), dizziness (13% vs. 6% on placebo), insomnia (13% vs. 6% on placebo), dry mouth (18% vs. 12% on placebo), constipation (14% vs. 9% on placebo), and tremor (8% vs. 2% on placebo).

Other side effects include high blood pressure, headache, agitation, weight gain, impaired memory and paresthesia, decreased fertility.


Acute overdosage is often manifested by emesis, lethargy, ataxia, tachycardia and seizures. Plasma, serum or blood concentrations of paroxetine may be measured to monitor therapeutic administration, confirm a diagnosis of poisoning in hospitalized patients or to aid in the medicolegal investigation of fatalities. Plasma paroxetine concentrations are generally in a range of 40–400 μg/L in persons receiving daily therapeutic doses and 200–2000 μg/L in poisoned patients. Postmortem blood levels have ranged from 1–4 mg/L in acute lethal overdose situations.

Pregnancy Issues

An analysis of World Health Organization data showing SSRIs taken during pregnancy may cause withdrawal symptoms, including convulsions, in newborn children: among "93 suspected cases of SSRI-induced neonatal withdrawal syndrome...64 were associated with paroxetine, 14 with fluoxetine, nine with sertraline, and seven with citalopram".

For pregnant women and women planning to become pregnant, "treatment with all SSRIs or selective norepinephrine reuptake inhibitors (or both) during pregnancy be individualized, and paroxetine use among pregnant women or women planning to become pregnant be avoided, if possible." According to the prescribing information "epidemiological studies have shown that infants born to women who had first trimester paroxetine exposure had an increased risk of cardiovascular malformations, primarily ventricular and atrial septal defects (VSDs and ASDs).

"The teratogenic potential of paroxetine that has been reported in some studies remains unproven." Gentile called for large, epidemiologic, prospective, controlled studies on "mothers who accept taking paroxetine during pregnancy". Other reviews vary on whether the teratogenic risks outweigh the risk of disease relapse if the drug is discontinued: some advocate discontinuation, while others suggest caution; even where the overview of antidepressants generally is favorable, paroxetine is singled out for specific risks. Paroxetine use during pregnancy increases the risk of spontaneous abortion.

Increased Suicide Risks

The FDA conducted a statistical analysis of paroxetine clinical trials in children and adolescents in 2004, finding an increase in "suicidality" and ideation as compared to placebo; the trend for increased "suicidality" was observed in both trials for depression and for anxiety disorders. A University of North Carolina review of SSRIs found the average risk of suicide among adolescents was 4%, versus 2% on placebo, and among all patients "the greatest risk of self-harm was among paroxetine users."

United Nations


Paroxetine is only available in the USA with a doctor's prescription. Statistics from 2007 show it's the fifth-most commonly prescribed anti-depressant drugs in America.


Other Countries


[1]Merck Index, fifteenth edition (2013)
Categories: Antidepressants, Category SSRI

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