Paroxetine

Key points

• Its elimination half-life runs from about 15 to 20 hours after a single dose.
• Its own metabolism is accomplished in part by the CYP2D6 liver enzyme.
• Each tablet’s sodium content is low enough that the label describes it as essentially sodium-free.

How it works

Studies at clinically relevant doses in humans have demonstrated that paroxetine blocks the uptake of serotonin into human platelets, and in vitro studies in animals suggest it is a potent and highly selective inhibitor of neuronal serotonin reuptake, with only weak effects on norepinephrine and dopamine neuronal reuptake. Its major metabolites are essentially inactive, since their relative potencies are at most 1/50 of the parent compound.

Safety specific to paroxetine

Antidepressants, including paroxetine, increased the risk of suicidal thinking and behaviour relative to placebo in children, adolescents and young adults during short-term studies of major depressive disorder and other psychiatric disorders, according to the PAXIL CR prescribing information. Anyone considering paroxetine for a child, adolescent or young adult must weigh this risk against the clinical need. Short-term studies did not show an increase in this risk with antidepressants relative to placebo in adults beyond age 24, and showed a reduction in risk in adults aged 65 and older, though depression and certain other psychiatric disorders are themselves associated with an increased risk of suicide. Patients of all ages starting antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality or unusual changes in behaviour, and families and caregivers should be advised of the need for close observation and communication with the prescriber. The extended-release brand PAXIL CR is not approved for use in paediatric patients, and paroxetine should not be used in the treatment of children and adolescents under 18 years of age.

Because a major depressive episode may be the initial presentation of bipolar disorder, this should be screened for before starting treatment. Paroxetine must not be combined with monoamine oxidase inhibitors (MAOIs), including the antibiotic linezolid, which acts as a reversible non-selective MAOI, or with thioridazine, and combination with pimozide is likewise contraindicated.

Paroxetine can cause serotonin syndrome, which is why the interactions above matter. The label describes symptoms that may include mental status changes such as agitation, hallucinations or coma, autonomic instability such as a fast or unstable heartbeat and raised temperature, neuromuscular changes such as exaggerated reflexes and loss of coordination, and gastrointestinal symptoms. In its most severe form it can resemble neuroleptic malignant syndrome, with high temperature, muscle rigidity, rapidly fluctuating vital signs and altered mental state. The label asks that patients be monitored for these signs and symptoms emerging.

In pregnancy, epidemiological studies have shown that infants exposed to paroxetine in the first trimester have an increased risk of congenital malformations, particularly cardiovascular malformations. Neonates exposed late in the third trimester to paroxetine or other SSRIs and serotonin and norepinephrine reuptake inhibitors have developed complications requiring prolonged hospitalisation, respiratory support and tube feeding.

Further reading

• PAXIL CR- paroxetine hydrochloride tablet, film coated, extended release
• Paroxetine 40 mg Tablets