What is the information about Paroxetine (SSRI)?

From the Guidelines

Paroxetine is a selective serotonin reuptake inhibitor (SSRI) that should be prescribed with caution due to its association with increased risk of suicidal thinking or behavior, discontinuation syndrome, and potential for drug-drug interactions. The medication is commonly used to treat depression, anxiety disorders, obsessive-compulsive disorder, post-traumatic stress disorder, and panic attacks. According to the most recent guideline evidence 1, paroxetine has special prescribing considerations, including the potential for discontinuation syndrome, which is characterized by symptoms such as dizziness, fatigue, and nausea.

When prescribing paroxetine, it is essential to start with a low dose and gradually increase it as needed, while monitoring for symptoms, especially in the first 24 to 48 hours after dosage changes 1. The typical starting dose for adults with depression is 20 mg once daily, which may be increased gradually to a maximum of 50 mg daily if needed. For anxiety disorders, dosing often starts lower at 10 mg daily.

Common side effects of paroxetine include nausea, drowsiness, dry mouth, insomnia, sexual dysfunction, and dizziness, which often improve over time 1. However, paroxetine has been associated with a higher risk of sexual dysfunction compared to other SSRIs 1. It is also important to note that paroxetine should not be stopped abruptly, as this can cause withdrawal symptoms; dosage should be tapered gradually under medical supervision.

In terms of potential interactions, paroxetine may interact with drugs metabolized by CYP2D6, and concomitant administration with monoamine oxidase inhibitors (MAOIs) is contraindicated due to the increased risk of serotonin syndrome 1. Overall, paroxetine can be an effective treatment option for various psychiatric conditions, but its use requires careful consideration of the potential risks and benefits, as well as close monitoring of patients, particularly during the initial treatment period.

From the FDA Drug Label

The efficacy of paroxetine in the treatment of major depressive disorder, social anxiety disorder, obsessive compulsive disorder (OCD), panic disorder (PD), generalized anxiety disorder (GAD), and posttraumatic stress disorder (PTSD) is presumed to be linked to potentiation of serotonergic activity in the central nervous system resulting from inhibition of neuronal reuptake of serotonin (5-hydroxy-tryptamine, 5-HT). Paroxetine is a potent and highly selective inhibitor of neuronal serotonin reuptake and has only very weak effects on norepinephrine and dopamine neuronal reuptake Paroxetine distributes throughout the body, including the CNS, with only 1% remaining in the plasma. Approximately 95% and 93% of paroxetine is bound to plasma protein at 100 ng/mL and 400 ng/mL, respectively.

Paroxetine (SSRI) Information:

• Indications: major depressive disorder, social anxiety disorder, obsessive compulsive disorder (OCD), panic disorder (PD), generalized anxiety disorder (GAD), and posttraumatic stress disorder (PTSD)
• Mechanism of Action: potentiation of serotonergic activity in the central nervous system resulting from inhibition of neuronal reuptake of serotonin (5-hydroxy-tryptamine, 5-HT)
• Pharmacokinetics: completely absorbed after oral dosing, extensively metabolized, and metabolites are considered to be inactive
• Protein Binding: approximately 95% and 93% of paroxetine is bound to plasma protein at 100 ng/mL and 400 ng/mL, respectively 2

From the Research

Overview of Paroxetine

• Paroxetine is a selective serotonin reuptake inhibitor (SSRI) with antidepressant and anxiolytic activity 3, 4, 5, 6, 7
• It is used to treat major depressive disorder, obsessive-compulsive disorder, panic disorder, social anxiety disorder, generalized anxiety disorder, and post-traumatic stress disorder in adults 3, 4, 5, 6, 7

Efficacy of Paroxetine

• Paroxetine has been shown to be effective in treating major depressive disorder, with a significant reduction in relapse or recurrence over 1 year 3, 4
• It is also effective in treating anxiety disorders, including obsessive-compulsive disorder, panic disorder, social anxiety disorder, and generalized anxiety disorder 3, 4, 5, 6, 7
• The efficacy of paroxetine is similar to that of other SSRIs and tricyclic antidepressants (TCAs) 3, 4, 5

Safety and Tolerability of Paroxetine

• Paroxetine is generally well tolerated, with a tolerability profile similar to that of other SSRIs 3, 4, 5
• Common adverse events include nausea, sexual dysfunction, somnolence, asthenia, headache, constipation, dizziness, sweating, tremor, and decreased appetite 3, 4, 5
• Paroxetine has been associated with an increased risk of congenital malformations, although this evidence is not conclusive 6
• It is not indicated for use in the pediatric population and is categorized as Pregnancy Class D 6

Pharmacokinetics and Pharmacodynamics of Paroxetine

• Paroxetine is a potent inhibitor of serotonin reuptake, with a high selectivity for the serotonin transporter 5
• It has a low affinity for other neurotransmitter systems, including norepinephrine, dopamine, and histamine 5
• Paroxetine is well absorbed orally and undergoes extensive first-pass metabolism, with a steady-state half-life of 21 hours 5