PAROXETINE

brands

Class

• Neuroscience-based Nomenclature: serotonin reuptake inhibitor (S-RI)
• SSRI (selective serotonin reuptake inhibitor); often classified as an antidepressant, but it is not just an antidepressant

PAROXETINE commonly prescribed for

(Bold for FDA approved)

How PAROXETINE works

• Boosts neurotransmitter serotonin

• Blocks serotonin reuptake pump (serotonin transporter)

• Desensitizes serotonin receptors, especially serotonin 1A autoreceptors

• Presumably increases serotonergic neurotransmission

• Paroxetine also has mild anticholinergic actions

• Paroxetine may have mild norepinephrine reuptake blocking actions

How long until PAROXETINE works

• Some patients may experience relief of insomnia or anxiety early after initiation of treatment

• Onset of therapeutic actions usually not immediate, but often delayed 2–4 weeks

• If it is not working within 6–8 weeks for depression, it may require a dosage increase or it may not work at all

• By contrast, for generalized anxiety, onset of response and increases in remission rates may still occur after 8 weeks of treatment and for up to 6 months after initiating dosing

• May continue to work for many years to prevent relapse of symptoms

Notable Side Effects

• Sexual dysfunction (dose-dependent; men: delayed ejaculation, erectile dysfunction; men and women: decreased sexual desire, anorgasmia)

• Gastrointestinal (decreased appetite, nausea, diarrhea, constipation, dry mouth)

• Mostly CNS (insomnia but also sedation, agitation, dose-dependent tremors, headache, dizziness)

• Weight gain

• Activation (short-term; patients with diagnosed or undiagnosed bipolar or psychotic disorders may be more vulnerable to CNS-activating actions of SSRIs

• Autonomic (dose-dependent sweating)

• Bruising and rare bleeding

• Syndrome of inappropriate antidiuretic hormone secretion (SIADH)

Life Threatening Side Effects

• Rare seizures

• Rare induction of mania

• Rare activation of suicidal ideation and behavior (suicidality) (short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo beyond age 24)

weight gain

not usual

sedation

common

What to do about PAROXETINE side effects

• Wait

• Wait

• Wait

• If paroxetine is sedating, take at night to reduce daytime drowsiness

• Reduce dose to 5–10 mg (12.5 mg for CR) until side effects abate, then increase as tolerated, usually to at least 20 mg (25 mg CR)

• In a few weeks, switch or add other drugs

usual dosage range

• Depression: 20–50 mg (25–62.5 mg CR)

• Vasomotor symptoms: 7.5 mg at bedtime

• Anxiety disorders and OCD: 10–60 mg/day (12.5–75 mg CR)

Dosage Forms

• Tablet 10 mg scored, 20 mg scored, 30 mg, 40 mg

• Controlled-release tablet 12.5 mg, 25 mg, 37.5 mg

• Capsule 7.5 mg

• Liquid 10 mg/5 mL – 250 mL bottle

long term use

• Safe

habit forming

• No

Renal Impairment

• Lower dose (initial 10 mg/day [12.5 mg CR], maximum 40 mg/day [50 mg/day CR])

Hepatic Impairment

• Lower dose (initial 10 mg/day [12.5 mg CR], maximum 40 mg/day [50 mg/day CR])

Cardiac Impairment

Preliminary research suggests that paroxetine is safe in these patients

• Treating depression with SSRIs in patients with acute angina or following myocardial infarction may reduce cardiac events and improve survival as well as mood

Elderly

• Lower dose (initial 10 mg/day [12.5 mg CR], maximum 40 mg/day [50 mg/day CR])

• Risk of SIADH with SSRIs is higher in the elderly

• Reduction in the risk of suicidality with antidepressants compared to placebo in adults age 65 and older

Children and Adolescents

• Carefully weigh the risks and benefits of pharmacological treatment against the risks and benefits of nontreatment with antidepressants and make sure to document this in the patient’s chart

• Monitor patients face-to-face regularly, particularly during the first several weeks of treatment

• Use with caution, observing for activation of known or unknown bipolar disorder and/ or suicidal ideation, and inform parents or guardians of this risk so they can help observe child or adolescent patients

• Not specifically approved, but preliminary evidence suggests possible efficacy in children and adolescents with OCD or social phobia

Pregnancy

• Effective June 30, 2015, the FDA requires changes to the content and format of pregnancy and lactation information in prescription drug labels, including the elimination of the pregnancy letter categories; the Pregnancy and Lactation Labeling Rule (PLLR or final rule) applies only to prescription drugs and will be phased in gradually for drugs approved on or after June 30, 2001

• Not generally recommended for use during pregnancy, especially during first trimester

• Epidemiological data have shown an increased risk of cardiovascular malformations (primarily ventricular and atrial septal defects) in infants born to women who took paroxetine during the first trimester (absolute risk is small)

• Unless the benefits of paroxetine to the mother justify continuing treatment, consider discontinuing paroxetine or switching to another antidepressant

• Paroxetine use late in pregnancy may be associated with higher risk of neonatal complications, including respiratory distress

• At delivery there may be more bleeding in the mother and transient irritability or sedation in the newborn

• Must weigh the risk of treatment (first trimester fetal development, third trimester newborn delivery) to the child against the risk of no treatment (recurrence of depression, maternal health, infant bonding) to the mother and child

• For many patients this may mean continuing treatment during pregnancy

• SSRI use beyond the 20th week of pregnancy may be associated with increased risk of pulmonary hypertension in newborns, although this is not proven

• Exposure to SSRIs late in pregnancy may be associated with increased risk of gestational hypertension and preeclampsia

• Neonates exposed to SSRIs or SNRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding; reported symptoms are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome, and include respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying

Breast Feeding

• Some drug is found in mother’s breast milk

• Trace amounts may be present in nursing children whose mothers are on paroxetine

• If child becomes irritable or sedated, breast feeding or drug may need to be discontinued

• Immediate postpartum period is a high-risk time for depression, especially in women who have had prior depressive episodes, so drug may need to be reinstituted late in the third trimester or shortly after childbirth to prevent a recurrence during the postpartum period

• Must weigh benefits of breast feeding with risks and benefits of antidepressant treatment versus nontreatment to both the infant and the mother

• For many patients, this may mean continuing treatment during breast feeding