Paroxetine is a selective serotonin reuptake inhibitor (SSRI), and, as such, is identified as an antidepressant. It is FDA approved for major depressive disorder (MDD), obsessive-compulsive disorder (OCD), social anxiety disorder (SAD), panic disorder, posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), and premenstrual dysphoric disorder (PMDD), vasomotor symptoms associated with menopause. Paroxetine is not FDA approved for use in children and adolescents less than 18 years of age; however, clinicians do use off-label in this group.
As an SSRI class drug, paroxetine's signature mechanism of action is to block the serotonin reuptake transporter (SERT) and thus increase the concentration of synaptic serotonin. Current theory suggests that the diminished serotonin concentration in the depressed brain induces the upregulation of serotonergic receptors. By increasing the synaptic serotonin concentration, paroxetine thus induces the downregulation of the previously upregulated serotonin receptors, thus normalizing the receptor concentration.  Furthermore, in a radioligand study, paroxetine showed some affinity for muscarinic, adrenergic (alpha and beta), dopaminergic (D2), serotonergic (5-HT2), and histaminergic (H1) receptors. These receptors have also appeared to contribute to its antidepressant effects, as well as its side effect profile.
Paroxetine is administered orally. The medication should be titrated based on the patient's symptoms and tolerance to dosage. The drug can be taken with or without food. In addition to regular tablets, it is available in a controlled-release tablet, as well as liquid form. Paroxetine may be administered at any time of the day, depending on toleration.
The steady-state mean values of T1/2 is 21 hours. Paroxetine undergoes metabolism via hepatic CYPP450 2D6. The urine excretes 2%, 62% metabolized over a 10-day post-dosing period, 36% excreted in the feces. Paroxetine inhibits CYP2D6 and, thus, its own metabolism; plasma concentrations can potentially double following dosage increases of 50%. 
For Major Depression 
Generalized Anxiety Disorder 
Immediate release formulas
Premenstrual Dysphoric Disorders 
Vasomotor Disorder Secondary to Menopause 
Controlled release tablets: 12.5 mg PO daily and titrated to 25 mg PO weekly
Obsessive-Compulsive Disorder 
Immediate release formulation
Panic Disorder 
Post Traumatic Stress Disorder 
Social Phobias 
Immediate release formulation
Controlled release formulation
Renal Impairment: Adults 
For patients with renal impairment, the dosage is based on creatinine clearance, as shown below.
Hepatic Impairment Adults 
In hepatic impairment, plasma concertation of two times normal can occur.
Many of the side effects of paroxetine are dose-dependent. The most common side effects include drowsiness, dry mouth, loss of appetite, sweating, sleep disturbance, and sexual side effects. Clinicians can address sexual side effects medications like sildenafil). Discontinuation syndrome is more common and more severe with paroxetine than with other SSRIs; this may be due in part to the fact that it inhibits its own metabolism. Withdrawal symptoms from discontinuation include dizziness, lethargy, nausea, vomiting, headache, fever, chills, vivid dreams, electric shock-like-sensation, dyskinesia, anxiety, crying, irritability, and depersonalization.
Other Adverse Effects
There are only a few absolute contraindications for the use of paroxetine. Absolute contraindications include concurrent use of monoamine oxidase inhibitors (MAOIs), thioridazine, and pimozide. Concomitant use of MAOIs and paroxetine can precipitate serotonin syndrome. Concurrent use of thioridazine and paroxetine can induce cardiac arrhythmias; similar effects can occur with pimozide and paroxetine.
Precautions that should be acknowledged when prescribing paroxetine include concurrent tricyclic antidepressant (TCA) use, concomitant tamoxifen use, and drugs affecting hepatic metabolism. Paroxetine inhibits TCA metabolism, leading to possible TCA toxicity. Tamoxifen is active once metabolized by CYP4502D6; thus, paroxetine essentially inactivates tamoxifen.
Paroxetine is not recommended for use during pregnancy or if breastfeeding. Based on epidemiological studies, infants exposed to paroxetine during the first trimester had an increased risk for cardiovascular malformations.
Patients initiated on paroxetine should receive close observation, initially, and monitored for worsening clinical symptoms, behavior changes (mania, social function, anxiety), or suicidal ideations. Labs should include serum sodium concentration to rule out SIADH. Vital signs should be monitored for signs of serotonergic hyperactivity. Serotonin syndrome precipitates via the manifestation of changes in mental status, autonomic instability, gastrointestinal symptoms, hyperreflexia, and myoclonus. Serotonin syndrome is treated by discontinuing any of the offending agents. If symptoms continue to escalate, the clinician can administer cyproheptadine.
Though it is rarely lethal in overdose by itself, patients can develop somnolence, nausea, tremor, heart rhythm disturbances, confusion, vomiting, dizziness, and mydriasis. During toxicity, a patient’s airway, oxygenation, and ventilation require evaluation first. The treatment for overdose includes symptomatic supportive treatment. There is no specific treatment for paroxetine toxicity.
Interprofessional teamwork can impact a patient's outcome positively. The increase in communication between the various department such as pharmacy and psychiatry can overall benefit the patient. Each department acknowledges what the patients' needs and implement the plan. The pharmacist can provide the dosing for the patient and monitor toxicity levels and consult with the prescriber for changes. Each patient is unique; some may require a different dosage because of renal of hepatic dysfunction. This approach allows the patient to have a correct dosage based on their co-morbid conditions. Nursing should be alert to signs of adverse drug events, improvement in status, or the need for further evaluation, and report such to the clinician. The psychiatrist can also monitor the patient clinically for improvement, or if needed, make changes in the medication. This interprofessional paradigm can improve patient outcomes through enhanced treatment strategies and information sharing. [Level 5]
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