Brand name: Paxil
Drug class: Selective Serotonin-reuptake Inhibitors
- Selective Serotonin-reuptake Inhibitors
- Serotonin-reuptake Inhibitors
- SSRIs
VA class: CN609
Chemical name: trans-(-)-3-[(1,3-Benzodioxol-5-yloxy)methyl]-4-(4-fluorophenyl)piperidine hydrochloride hemihydrate
Molecular formula: C₁₉H₂₀FNO₃•HCl•½H₂O
CAS number: 110429-35-1

Medically reviewed by Drugs.com on Apr 4, 2022. Written by ASHP.

Introduction

Antidepressant; selective serotonin-reuptake inhibitor (SSRI).

Uses for PARoxetine

Major Depressive Disorder

Management of major depressive disorder.

Efficacy in hospital settings not established.

Obsessive-Compulsive Disorder (OCD)

Management of OCD; SSRIs reduce but do not completely eliminate obsessions and compulsions.

Panic Disorder

Management of panic disorder with or without agoraphobia.

Social Phobia

Management of social phobia (social anxiety disorder).

Anxiety Disorders

Management of generalized anxiety disorder.

Posttraumatic Stress Disorder (PTSD)

Management of PTSD (alone or in combination with psychotherapy).

Premenstrual Dysphoric Disorder (PMDD)

Management of PMDD.

Premature Ejaculation

Has been used for the management of premature ejaculation^{† [off-label]}.

Diabetic Neuropathy

Has been used for the management of diabetic neuropathy^{† [off-label]}.

Chronic Headache

Has been used for the management of chronic headache^{† [off-label]}.

PARoxetine Dosage and Administration

General

• Allow at least 2 weeks to elapse between discontinuance of an MAO inhibitor intended to treat psychiatric disorders and initiation of paroxetine, and vice versa. (See Contraindications and Serotonin Syndrome under Cautions and also see Specific Drugs under Interactions.)

• Monitor for possible worsening of depression, suicidality, or unusual changes in behavior, especially at the beginning of therapy or during periods of dosage adjustments. (See Worsening of Depression and Suicidality Risk under Cautions.)

• Sustained therapy may be required; periodically reassess for need for continued therapy.

• Avoid abrupt discontinuance of therapy; to avoid withdrawal reactions, taper dosage gradually over a period of several weeks. (See Withdrawal of Therapy under Cautions.)

Administration

Oral Administration

Administer orally once daily (in the morning) without regard to meals; however, administration with food may minimize adverse GI effects.

Shake oral suspension well just prior to administration.

Swallow extended-release tablets whole; do not chew or crush.

Dosage

Available as paroxetine hydrochloride; dosage expressed in terms of paroxetine.

Adults

Major Depressive Disorder

Oral

Conventional tablets or suspension: Initially, 20 mg once daily. If no improvement, dosage may be increased in 10-mg increments at weekly intervals.

Extended-release tablets: Initially, 25 mg once daily. If no improvement, dosage may be increased in 12.5-mg increments at weekly intervals.

Optimum duration not established; may require several months of therapy or longer. Antidepressant efficacy demonstrated for up to 1 year at mean dosage of 30 mg daily as conventional tablets or suspension, which corresponds to a 37.5 mg daily dosage as extended-release tablets.

Obsessive-Compulsive Disorder

Oral

Conventional tablets or suspension: Initially, 20 mg once daily. If no improvement, dosage may be increased in 10-mg increments at weekly intervals, to 40 mg daily.

Optimum duration not established; efficacy has been demonstrated in a 6-month relapse prevention trial. Obsessive-compulsive disorder is chronic and requires several months or longer of sustained therapy. May continue therapy in responding patients, but use lowest effective dosage and periodically reassess need for continued therapy.

Panic Disorder

Oral

Conventional tablets or suspension: Initially, 10 mg once daily. If no improvement, dosage may be increased in 10-mg increments at weekly intervals, to 40 mg daily.

Extended-release tablets: Initially, 12.5 mg once daily. If no improvement, dosage may be increased in 12.5-mg increments at weekly intervals.

Optimum duration not established; efficacy demonstrated in a 3-month relapse prevention trial. May continue therapy in responding patients, but use lowest effective dosage and periodically reassess need for continued therapy.

Social Phobia

Oral

Conventional tablets or suspension: 20 mg once daily; no additional clinical benefit was observed with higher dosages.

Extended-release tablets: Initially, 12.5 mg once daily. If dosage is increased, use 12.5-mg increments at weekly intervals.

Long-term efficacy (>12 weeks) not demonstrated; may consider continuation in patient who responds, but use lowest effective dosage and periodically reassess need for continued therapy.

Anxiety Disorders

Oral

Conventional tablets or suspension: Initially, 20 mg daily; no additional clinical benefit was observed with higher dosages. If needed, dosage may be increased in 10-mg increments at weekly intervals.

Optimum duration not established; efficacy has been demonstrated in a 24-week relapse prevention trial. Generalized anxiety disorder is chronic. May continue therapy in responding patients. If used for extended periods, adjust dosage so that patients are maintained on lowest effective dosage and periodically reassess need for continued therapy.

Posttraumatic Stress Disorder

Oral

Conventional tablets or suspension: 20 mg daily; insufficient evidence to suggest greater clinical benefit with higher dosages. If needed, dosage may be increased in 10-mg increments at weekly intervals.

Consider alternative therapy if patient fails to achieve ≥25% reduction in PTSD symptoms at week 8. If >75% reduction in PTSD symptoms and response maintained for ≥3 months, may consider up to 24 months of drug therapy. If used for extended periods, adjust dosage so that patients are maintained on lowest effective dosage and periodically reassess need for continued therapy.

Premenstrual Dysphoric Disorder

Oral

Conventional tablets or suspension^{† [off-label]}: 5–30 mg daily.

Extended-release tablets: Initially, 12.5 mg once daily; may be administered daily throughout menstrual cycle or only during luteal phase. Dosage may be increased in intervals of ≥1 week. Dosages of 12.5–25 mg were effective in clinical studies.

Premature Ejaculation† [off-label]

Oral

Conventional tablets or suspension: 10–40 mg once daily. Alternatively, 20 mg taken 3–4 hours before planned intercourse on an “as needed” basis.

Diabetic Neuropathy†

Oral

Conventional tablets or suspension: 40 mg daily.

Chronic Headache†

Oral

Conventional tablets or suspension: 10–50 mg daily for 3–9 months.

Prescribing Limits

Adults

Major Depressive Disorder

Oral

Conventional tablets or suspension: Maximum 50 mg daily.

Extended-release tablets: 62.5 mg daily.

Obsessive-Compulsive Disorder

Oral

Conventional tablets or suspension: Maximum 60 mg daily.

Panic Disorder

Oral

Conventional tablets or suspension: Maximum 60 mg daily.

Extended-release tablets: 75 mg daily.

Social Phobia

Oral

Extended-release tablets: 37.5 mg daily.

Special Populations

Hepatic Impairment

Oral

In patients with severe hepatic impairment, an initial dosage of 10 mg daily (as conventional tablets or suspension) or 12.5 mg daily (as extended-release tablets). If no clinical improvement is apparent, dosage may be titrated with caution up to a maximum of 40 mg daily (for conventional tablets or suspension) or 50 mg (for extended-release tablets).

Renal Impairment

Oral

In patients with severe renal impairment, an initial dosage of 10 mg daily (as conventional tablets or suspension) or 12.5 mg daily (as extended-release tablets). If no clinical improvement is apparent, dosage may be titrated with caution up to a maximum of 40 mg daily (for conventional tablets or suspension) or 50 mg (for extended-release tablets).

Geriatric or Debilitated Patients

Initially, 10 mg daily (as conventional tablets or suspension) or 12.5 mg daily (as extended-release tablets); if no clinical improvement is apparent, dosage may be titrated up to a maximum of 40 mg daily (as conventional tablets or suspension) or 50 mg daily (as extended-release tablets).

Cautions for PARoxetine

Contraindications

• Paroxetine is contraindicated in patients who are currently receiving or have recently (i.e., within 2 weeks) received therapy with an MAO inhibitor intended to treat psychiatric disorders. Conversely, MAO inhibitors intended to treat psychiatric disorders are contraindicated within 2 weeks of paroxetine discontinuance. (See Serotonin Syndrome under Cautions and also see Specific Drugs under Interactions.)

• Initiation of paroxetine is contraindicated in patients receiving MAO inhibitors such as linezolid or IV methylene blue. (See Specific Drugs under Interactions.)

• Concurrent therapy with thioridazine. (See Drug Interaction with Thioridazine under Warnings.)

• Concurrent pimozide therapy. (See Interactions.)

• Known hypersensitivity to paroxetine or any ingredient in the formulation.

Warnings/Precautions

Warnings

Worsening of Depression and Suicidality Risk

Possible worsening of depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior in both adult and pediatric patients with major depressive disorder, whether or not they are taking antidepressants; may persist until clinically important remission occurs. However, suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide.

Appropriately monitor and closely observe patients receiving paroxetine for any reason, particularly during initiation of therapy (i.e., the first few months) and during periods of dosage adjustments. (See Boxed Warning and also see Pediatric Use under Cautions.)

Anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and/or mania may be precursors to emerging suicidality. Consider changing or discontinuing therapy in patients whose depression is persistently worse or in those with emerging suicidality or symptoms that might be precursors to worsening depression or suicidality, particularly if severe, abrupt in onset, or not part of patient’s presenting symptoms. If decision is made to discontinue therapy, taper paroxetine dosage as rapidly as is feasible but consider risks of abrupt discontinuance. (See General under Dosage and Administration.)

Prescribe in smallest quantity consistent with good patient management to reduce risk of overdosage.

Observe these precautions for patients with psychiatric (e.g., major depressive disorder, obsessive-compulsive disorder) or nonpsychiatric disorders.

Bipolar Disorder

May unmask bipolar disorder. (See Activation of Mania or Hypomania under Cautions.) Paroxetine is not approved for use in treating bipolar depression.

Screen for risk of bipolar disorder by obtaining detailed psychiatric history (e.g., family history of suicide, bipolar disorder, depression) prior to initiating therapy.

Serotonin Syndrome

Potentially life-threatening serotonin syndrome reported with SSRIs and SNRIs alone, but particularly during concurrent therapy with other serotonergic drugs (e.g., 5-HT₁ receptor agonists [“triptans”], TCAs, amphetamines, buspirone, fentanyl, lithium, tramadol, tryptophan, St. John's wort [Hypericum perforatum]) and with drugs that impair the metabolism of serotonin (particularly MAO inhibitors, both those used to treat psychiatric disorders and others, such as linezolid and methylene blue). (See Interactions.)

Symptoms of serotonin syndrome may include mental status changes (e.g., agitation, hallucinations, delirium, coma), autonomic instability (e.g., tachycardia, labile BP, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or GI symptoms (e.g., nausea, vomiting, diarrhea).

Paroxetine is contraindicated in patients who are currently receiving or have recently (i.e., within 2 weeks) received therapy with MAO inhibitors intended to treat psychiatric disorders. Do not initiate paroxetine in patients treated with other MAO inhibitors such as linezolid or IV methylene blue. (See Specific Drugs under Interactions.)

If concurrent therapy with other serotonergic drugs is clinically warranted, advise patient of potentially increased risk for serotonin syndrome, particularly during initiation of therapy and dosage increases.

Monitor patients receiving paroxetine for the development of serotonin syndrome. If manifestations occur, immediately discontinue paroxetine and any concurrently administered serotonergic agents and initiate supportive and symptomatic treatment.

Drug Interaction with Thioridazine

May inhibit CYP2D6, resulting in increased risk of QT-interval prolongation and/or ventricular tachycardia of the torsades de pointes type associated with elevated plasma concentrations of thioridazine. (See Contraindications.)

Fetal/Neonatal Morbidity and Mortality

May increase risk of fetal defects (e.g., cardiovascular malformations, principally ventricular and atrial septal defects; other major congenital malformations) when administered to pregnant women.

If a patient becomes pregnant during treatment, advise patient of the potential hazard to the fetus. Unless the potential benefits to the mother justify continuing treatment, consider discontinuing paroxetine therapy or switching to another antidepressant. (See General under Dosage and Administration.) For women who intend to become pregnant or are in their first trimester of pregnancy, initiate paroxetine only after consideration of other available treatment options.

Possible complications, sometimes severe and requiring prolonged hospitalization, respiratory support, enteral nutrition, and other forms of supportive care in neonates exposed to paroxetine, other SSRIs, or SNRIs late in the third trimester; may arise immediately upon delivery.

Conflicting findings from available studies evaluating possible risk of persistent pulmonary hypertension of the newborn (PPHN) following in utero exposure to SSRIs; currently unclear whether SSRI use during pregnancy can cause PPHN.

Carefully consider both the potential risks and benefits of treatment when used during the third trimester of pregnancy. Be aware that in a longitudinal study involving women with a history of major depressive disorder who were euthymic while receiving antidepressant therapy at the beginning of pregnancy, women who discontinued antidepressant therapy during pregnancy were more likely to experience a relapse of depression than those who remained on antidepressant therapy.

Consult joint APA and ACOG guidelines (at [Web]) for additional information on management of depression in women prior to conception and during pregnancy, including treatment algorithms.

General Precautions

Activation of Mania or Hypomania

Possible activation of mania or hypomania. Use with caution in patients with a history of mania. (See Bipolar Disorder under Cautions.)

Seizures

Seizures have been reported. Limited experience with use of paroxetine in patients with a history of seizures; use with caution in such patients. Discontinue if seizures occur.

Akathisia

Akathisia has been reported. Most likely to occur within the first few weeks of therapy.

Hyponatremia

May occur secondary to SIADH; apparently reversible following discontinuance of the drug and/or fluid restriction. Occurs mainly in older patients and those receiving diuretics or otherwise volume depleted. (See Geriatric Use under Cautions.)

Abnormal Bleeding

Possible increased risk of bleeding, including upper GI bleeding; use with caution.

Concomitant use of an NSAIA (e.g., aspirin) or warfarin may potentiate such risk.

Concomitant Disease

May be less cardiotoxic than most older antidepressant agents but experience is limited in patients with recent MI or unstable heart disease. Use with caution.

May cause mydriasis. Use with caution in patients with angle-closure glaucoma.

Cognitive and Motor Performance

Does not appear to produce substantial cognitive or motor impairment, but patients should be cautioned to avoid activities requiring alertness or physical coordination until effects on individual are known.

Withdrawal of Therapy

Possible withdrawal reactions following abrupt discontinuance or intermittent noncompliance with therapy. Avoid abrupt discontinuance of therapy; taper dosage gradually over a period of several weeks.

If intolerable symptoms occur, reinstitute at the previously prescribed dosage until such symptoms abate. Clinicians may resume dosage reductions at that time but at a more gradual rate.

Electroconvulsive Therapy (ECT)

Effects of concomitant use with ECT have not been systematically evaluated.

Specific Populations

Pregnancy

See Fetal/Neonatal Morbidity and Mortality under Cautions.

Effect of paroxetine on labor and delivery unknown. However, there have been postmarketing reports of premature births in pregnant women who have received paroxetine or other SSRIs.

Lactation

Distributed into human milk; use with caution.

Pediatric Use

Safety and efficacy not established in children <18 years of age.

FDA warns that a greater risk of suicidal thinking or behavior (suicidality) occurred during the first few months of antidepressant treatment compared with placebo in children and adolescents with major depressive disorder, obsessive-compulsive disorder (OCD), or other psychiatric disorders based on pooled analyses of 24 short-term, placebo-controlled trials of 9 antidepressant drugs (SSRIs and others). However, a more recent meta-analysis of 27 placebo-controlled trials of 9 antidepressants (SSRIs and others) in patients <19 years of age with major depressive disorder, OCD, or non-OCD anxiety disorders suggests that the benefits of antidepressant therapy in treating these conditions may outweigh the risks of suicidal behavior or suicidal ideation. No suicides occurred in these pediatric trials.

Carefully consider these findings when assessing potential benefits and risks of paroxetine in a child or adolescent for any clinical use. (See Suicidality in the Boxed Warning and also see Worsening of Depression and Suicidality Risk under Cautions.)

Geriatric Use

Possible decreased clearance; however, efficacy and adverse effects similar to those in younger adults. Initiate therapy at a lower dosage. (See Geriatric or Debilitated Patients under Dosage and Administration.)

May be more likely than younger patients to develop hyponatremia and transient SIADH. Periodically monitor serum sodium concentrations, especially during the first several months of therapy.

In pooled data analyses, a reduced risk of suicidality was observed in adults ≥65 years of age with antidepressant therapy compared with placebo. (See Boxed Warning and also see Worsening of Depression and Suicidality Risk under Cautions.)

Hepatic Impairment

Increased plasma concentrations and decreased clearance reported. Use with caution; use at a reduced initial dosage if impairment is severe. (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Increased plasma concentrations and decreased clearance reported. Use with caution; use at a reduced initial dosage if impairment is severe. (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Nervous system effects (e.g., asthenia, somnolence, dizziness, insomnia, tremor, nervousness), GI effects (e.g., nausea, decreased appetite, constipation, dry mouth), impotence, ejaculatory dysfunction, female genital disorders (e.g., anorgasmia or difficulty reaching climax/orgasm), sweating.

Interactions for PARoxetine

Metabolized partially by CYP2D6. Inhibits the activity of CYP2D6 and to a lesser extent CYP3A4.

Drugs Metabolized by Hepatic Microsomal Enzymes

Substrates of CYP2D6 or CYP3A4: possible increased plasma concentrations of the substrates.

Use with caution and consider reducing dosage of concomitantly administered CYP2D6 substrate, particularly those with a narrow therapeutic index, such as TCAs, class IC antiarrhythmics, and some phenothiazines.

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors or inducers of CYP isoenzymes (e.g., CYP2D6): potential pharmacokinetic interaction (altered paroxetine metabolism and plasma concentrations).

Drugs Associated with Serotonin Syndrome

Potentially life-threatening serotonin syndrome with other serotonergic drugs. If concomitant use of other serotonergic drugs with paroxetine is clinically warranted, advise patients of the increased risk for serotonin syndrome, particularly during treatment initiation and dosage increases.

If serotonin syndrome occurs, immediately discontinue paroxetine and any concurrently administered serotonergic agents; initiate supportive and symptomatic treatment. (See Serotonin Syndrome under Cautions.)

Drugs Affecting Hemostasis

Potential pharmacologic interaction (increased risk of bleeding) with concomitant use of drugs that affect hemostasis. Use with caution.

Specific Drugs

PARoxetine Pharmacokinetics

Absorption

Bioavailability

Completely absorbed following oral administration.

Oral bioavailability in humans not fully elucidated to date.

Equally bioavailable from commercially available conventional tablets and suspension.

Food

Food does not substantially affect the absorption of paroxetine.

Special Populations

In geriatric patients, trough paroxetine concentrations are 70–80% greater than in younger patients.

In patients with renal impairment (Cl_cr <30 mL/minute), mean plasma paroxetine concentrations are approximately 4 times greater than those seen in healthy individuals.

Hepatic impairment may increase plasma concentrations twofold.

Distribution

Extent

Widely distributed in the body, including the CNS and breast milk.

Plasma Protein Binding

≥93%

Elimination

Metabolism

Extensively metabolized, partially by CYP2D6. Metabolites are essentially inactive. Inhibits activity of CYP2D6.

Elimination Route

Eliminated principally in urine and feces (probably via bile).

Half-life

Averages approximately 21–24 hours.

Special Populations

In geriatric individuals, elimination half-life may be increased (e.g., to about 36 hours).

Stability

Storage

Oral

Conventional Tablets

15–30°C.

Extended-release Tablets

≤25°C.

Suspension

≤25°C.

Actions

• Mechanism of action as an antidepressant is presumed to be linked to potentiation of serotonergic activity in the CNS resulting from its inhibition of CNS neuronal reuptake of serotonin (5-HT).

• Has little or no effect on other neurotransmitters or any clinically important anticholinergic, antihistaminic, or adrenergic (α₁, α₂, β) blocking activity at usual therapeutic dosages.

• Generally less sedating than most older antidepressants.

Advice to Patients

• Importance of providing copy of written patient information (medication guide) each time paroxetine is dispensed. Importance of advising patients to read the patient information before taking paroxetine and each time the prescription is filled.

• Risk of suicidality; importance of patients, caregivers, and families being alert to and immediately reporting emergence of suicidality, worsening depression, or unusual changes in behavior, especially during the first few months of therapy or during periods of dosage adjustment. (See Worsening of Depression and Suicidality Risk under Cautions.)

• Potential risk of serotonin syndrome, particularly with concurrent use of paroxetine and 5-HT₁ receptor agonists (also called triptans), tramadol, tryptophan, other serotonergic agents, or antipsychotic agents. Importance of immediately contacting clinician if manifestations of serotonin syndrome develop (e.g., restlessness, hallucinations, delirium, loss of coordination, fast heart beat, increased body temperature, sweating, muscle stiffness, labile BP, diarrhea, coma, nausea, vomiting, confusion).

• Importance of continuing therapy even if improvement is not evident for 4 weeks, unless directed otherwise by clinician.

• Importance of avoiding some activities (e.g., operating machinery, driving a motor vehicle) until effects on the individual are known.

• Importance of patients informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, or of use of alcohol-containing beverages or products.

• Risk of fetal harm. Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. If a woman becomes pregnant while receiving paroxetine, inform her of the potential hazard to the fetus. Unless the potential benefits to the mother justify continuing treatment, consider either discontinuing paroxetine therapy or switching to another antidepressant. For women who intend to become pregnant or are in their first trimester of pregnancy, initiate paroxetine only after consideration of other available treatment options. (See Pregnancy under Cautions.)

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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Frequently asked questions

• SSRI’s vs SNRI’s - What's the difference between them?
• What are some common side effects of antidepressants?

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