Description

Simple

A medication used to treat depression, anxiety, OCD, and PTSD, as well as the symptoms of menopause such as hot flashes.

Clinical

A selective serotonin reuptake inhibitor used to treat major depressive disorder, panic disorder, OCD, social phobia, generalized anxiety disorder, the vasomotor symptoms of menopause, and premenstrual dysphoric disorder.

Overview

Paroxetine is a selective serotonin reuptake inhibitor (SSRI) drug commonly known as Paxil. It has a variety of uses, including the treatment of anxiety disorders, major depression, posttraumatic stress disorder, and symptoms of menopause, among others.[26] It was approved by the FDA in the early 1990s and marketed by SmithKline Beecham.[32,33] A unique feature of this drug is that it is highly potent and selective in its inhibition of serotonin reuptake and has little effect on other neurotransmitters.[13] Because of its potent inhibition of serotonin reuptake, paroxetine is more likely to cause withdrawal effects upon cessation. Paroxetine is well tolerated in most patients with a similar adverse effect profile to other members of its drug class.[Read more

Paroxetine is a selective serotonin reuptake inhibitor (SSRI) drug commonly known as Paxil. It has a variety of uses, including the treatment of anxiety disorders, major depression, posttraumatic stress disorder, and symptoms of menopause, among others.[26] It was approved by the FDA in the early 1990s and marketed by SmithKline Beecham.[32,33] A unique feature of this drug is that it is highly potent and selective in its inhibition of serotonin reuptake and has little effect on other neurotransmitters.[13] Because of its potent inhibition of serotonin reuptake, paroxetine is more likely to cause withdrawal effects upon cessation. Paroxetine is well tolerated in most patients with a similar adverse effect profile to other members of its drug class.[13] The controlled release formulation was designed to decrease the likelihood of nausea that is sometimes associated with paroxetine.[28,36] Read Less

Pharmacology

Indication

Paroxetine is indicated for the management of depression, obsessive-compulsive disorder, panic disorder, social anxiety disorder, generalized anxiety disorder, posttraumatic stress disorder.[29] One form of paroxetine,... Read more

Paroxetine is indicated for the management of depression, obsessive-compulsive disorder, panic disorder, social anxiety disorder, generalized anxiety disorder, posttraumatic stress disorder.[29] One form of paroxetine, commercially known as Brisdelle, is used to manage mild to moderate vasomotor symptoms of menopause.[30] Off-label, paroxetine may be used for the treatment of premature ejaculation or irritable bowel syndrome (IBS).[4,5,24] Read Less

Pharmacodynamic

Paroxetine treats the symptoms of depression, various anxiety disorders, posttraumatic stress disorder, obsessive-compulsive disorder, and the vasomotor symptoms of menopause via the inhibition of serotonin reuptake.[ Read more

Paroxetine treats the symptoms of depression, various anxiety disorders, posttraumatic stress disorder, obsessive-compulsive disorder, and the vasomotor symptoms of menopause via the inhibition of serotonin reuptake.[26,29,30] The onset of action of paroxetine is reported to be approximately 6 weeks.[19]

Due its serotonergic activity, paroxetine, like other SSRI drugs, may potentiate serotonin syndrome. This risk is especially high when monoamine oxidase (MAO) inhibitors are given within 2 weeks of paroxetine administration. Upon cessation of MAO inhibitors, a 2-week interval before paroxetine administration is recommended. Do not coadminister these agents.[27] Read Less

Mechanism of action

Paroxetine enhances serotonergic activity via the inhibition presynaptic reuptake of serotonin by the serotonin (SERT) receptor.[ Read more

Paroxetine enhances serotonergic activity via the inhibition presynaptic reuptake of serotonin by the serotonin (SERT) receptor.[21,11] This inhibition raises the level of serotonin in the synaptic cleft, relieving various symptoms. This drug has been demonstrated to be a stronger inhibitor of serotonin reuptake than other members of the same drug class, including [Citalopram], [Fluoxetine], and [Fluvoxamine].[13] The mechanism of action of paroxetine in relieving the vasomotor symptoms of menopause is unknown, according to the Brisdelle prescribing information[30], but may occur due to its effects on thermoregulation.[25]

Paroxetine shows a clinically insignificant affinity for adrenergic alpha-1 and alpha-2 receptors and β-adrenergic receptors, dopamine D1 and D2 receptors, histamine H1 receptors and serotonin 5-HT1A, 5-HT2A and 5-HT2C receptors.[13] This drug shows some affinity for muscarinic cholinergic receptors and 5-H2B receptors.[22,23] The delayed onset of paroxetine therapeutic effects may be explained by the initial paroxetine actions on the 5-HT neurons. In rats, paroxetine activates 5-HT1A receptors when it is first administered, inhibiting the stimulation of the 5-HT neurons and subsequent release of serotonin at the synaptic cleft.[13] Read Less

Absorption

Paroxetine is readily absorbed from the gastrointestinal tract. Due to the first-pass metabolism, the bioavailability ranges from 30-60%. Cmax is attained 2 to 8 hours after an oral dose.[ Read more

Paroxetine is readily absorbed from the gastrointestinal tract. Due to the first-pass metabolism, the bioavailability ranges from 30-60%. Cmax is attained 2 to 8 hours after an oral dose.[7] Mean Tmax is 4.3 hours in healthy patients.[31] The steady-state concentration of paroxetine is achieved within 7 to 14 days of oral therapy.[13] In a pharmacokinetic study, AUC in healthy patients was 574 ng·h/mL and 1053 ng·h/mL in those with moderate renal impairment.[31] Read Less

Protein binding

Paroxetine is 95% bound to plasma proteins.[7, Read more

Paroxetine is 95% bound to plasma proteins.[7,14,29] Read Less

Volume of distribution

Paroxetine has a large volume of distribution and is found throughout the body, including in the central nervous system. Only 1% of the drug is found in the plasma.[29]Paroxetine is found in the breast milk at concent... Read more

Paroxetine has a large volume of distribution and is found throughout the body, including in the central nervous system. Only 1% of the drug is found in the plasma.[29]Paroxetine is found in the breast milk at concentrations similar to the concentrations found in plasma.[13] Read Less

Clearance

The apparent oral clearance of paroxetine is 167 L/h.[14] The clearance... Read more

The apparent oral clearance of paroxetine is 167 L/h.[14] The clearance of paroxetine in patients with renal failure is significantly lower and dose adjustment may be required, despite the fact that it is mainly cleared by the liver. Dose adjustments may be required in hepatic impairment.[14,29,31] Read Less

Half life

The mean elimination half-life of paroxetine is about 21 hours.[29] In healthy young subjects, mean elimination half-life was found to be 17.3 hours.[ Read more

The mean elimination half-life of paroxetine is about 21 hours.[29] In healthy young subjects, mean elimination half-life was found to be 17.3 hours.[31] One resource mentions the half-life ranges from 1-4 days.[15] Read Less

Route of elimination

About 2/3 of a single paroxetine dose is found to be excreted in the urine and the remainder is found to be excreted in feces. Almost all of the dose is eliminated as metabolites; 3% is found to be excreted as unchanged paroxetine.[ Read more

About 2/3 of a single paroxetine dose is found to be excreted in the urine and the remainder is found to be excreted in feces. Almost all of the dose is eliminated as metabolites; 3% is found to be excreted as unchanged paroxetine.[13] About 64% of a 30 mg oral dose was found excreted in the urine, with 2% as the parent drug and 62% appearing as metabolites. Approximately 36% of the dose was found to be eliminated in the feces primarily as metabolites and less than 1% as the parent compound.[29] Read Less

Toxicity

The acute LD50 in mice and rats is 350 mg/kg.[35]

Overdose information

The lowest dose of paroxetine reported to lead to a fatal outcome is approximately 400 mg. The largest reported paroxetine overdose fr... Read more

The acute LD50 in mice and rats is 350 mg/kg.[35]

Overdose information

The lowest dose of paroxetine reported to lead to a fatal outcome is approximately 400 mg. The largest reported paroxetine overdose from which a patient has survived and recovered is a dose of 2000 mg. Common manifestations in a paroxetine overdose include fatigue, fever, insomnia hypertension, tachycardia, nausea, vomiting, somnolence, tremor, dizziness, agitation, confusion, anxious symptoms, headache, insomnia, hyperhidrosis, dilated pupils, seizures, paresthesia, serotonin syndrome, involuntary muscle contraction, and change in mental status. It should be noted that in some cases, patients may have consumed alcohol in addition to taking an overdose of paroxetine.[31] Some of these symptoms may also be seen with clinical use. There is no specific antidote to an overdose of paroxetine.[12] Read Less

Adverse Effects

Contraindications