Version July 2025
IR tablets, suspension; ER tablets: Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening and for emergence of suicidal thoughts and behaviors. Paroxetine is not approved for use in pediatric patients.
IR capsules: Selective serotonin reuptake inhibitors (SSRIs) increased the risk of suicidal thoughts and behavior in pediatric and young adult patients in short-term trials for the treatment of major depressive disorder and other psychiatric disorders. Because paroxetine is an SSRI, closely monitor paroxetine-treated patients closely for emergence of suicidal thoughts and behaviors. Brisdelle is not approved for use in any psychiatric condition or in pediatric and young adult patients.
Dosage guidance:
Dosing: Some experts suggest a lower starting dose of 5 to 10 mg once daily (immediate release) or 12.5 mg once daily (extended release) and gradual titration in increments of ≤10 mg (immediate release) or 12.5 mg (extended release), particularly in patients with anxiety who are sensitive to antidepressant-associated overstimulation effects (eg, anxiety, insomnia) (Ref).
Dosage form information: Paroxetine is available as IR and ER formulations; both formulations are dosed once daily but are not interchangeable on a milligram to milligram basis. Where dosing for the ER formulation is not provided for an indication, may convert between formulations using equivalence shown in "Dosing conversions" section below.
Body dysmorphic disorder (alternative agent) (off-label use): Immediate release: Oral: Initial: 20 mg once daily; may increase dose gradually based on response and tolerability in increments of 20 mg/day at intervals of every 2 to 3 weeks to a usual dose of 60 mg/day; doses up to 100 mg/day, if tolerated, may be necessary in some patients for optimal response (Ref). Note: An adequate trial for assessment of effect is 12 to 16 weeks, including a dose of 60 mg for at least 4 of those weeks, if needed and tolerated (Ref).
Generalized anxiety disorder: Immediate release: Oral: Initial: 10 to 20 mg once daily; may increase dose based on response and tolerability in increments of 10 mg/day at intervals ≥1 week up to 50 mg/day (Ref). Doses may be increased every 3 to 4 days if warranted in inpatient settings. Some experts recommend maintaining the initial therapeutic dose day for 4 to 6 weeks to assess for efficacy before increasing further (Ref).
Major depressive disorder (unipolar):
Immediate release: Oral: Initial: 20 mg once daily; may increase dose based on response and tolerability in increments of 10 to 20 mg/day at intervals ≥1 week to a maximum of 50 mg/day. Usual dose: 20 to 40 mg/day (Ref).
Extended release: Oral: Initial: 25 mg once daily; may increase dose based on response and tolerability in increments of 12.5 mg/day at intervals ≥1 week to a maximum of 62.5 mg/day. Usual dose: 25 to 50 mg/day (Ref).
Obsessive-compulsive disorder: Immediate release: Oral: Initial: 20 mg once daily; may increase dose based on response and tolerability in increments of 10 mg/day at intervals ≥1 week up to a recommended dose of 40 to 60 mg/day; maximum dose: 60 mg/day (Ref). Some experts recommend doses as high as 100 mg/day when lower doses are well-tolerated but ineffective (Ref). Note: An adequate trial for assessment of effect in obsessive-compulsive disorder is considered ≥6 weeks at the maximum tolerated dose (Ref).
Panic disorder:
Immediate release: Oral: Initial: 10 mg once daily for 3 to 7 days; may increase dose based on response and tolerability in increments of 10 mg/day at intervals ≥1 week up to a usual dose of 20 to 40 mg/day (Ref); maximum dose: 60 mg/day. Some experts maintain dose at 20 mg for 4 weeks before considering further dose increases. May require 6 weeks at maximally tolerated dose for adequate treatment trial (Ref).
Extended release: Oral: Initial: 12.5 mg once daily; may increase dose based on response and tolerability in increments of 12.5 mg/day at intervals ≥1 week up to a maximum of 75 mg/day. Some experts maintain dose at 25 mg for 4 weeks before considering further dose increases. May require 6 weeks at maximally tolerated dose for adequate treatment trial (Ref).
Posttraumatic stress disorder: Immediate release: Oral: Initial: 20 mg once daily; may increase dose based on response and tolerability in increments of 10 to 20 mg/day at intervals ≥1 week up to 60 mg/day (Ref).
Premature ejaculation (off-label use): Immediate release: Oral: Initial: 10 mg once daily; may increase dose based on response and tolerability in increments of 10 mg/day at intervals ≥1 week to a usual dosage of 20 mg/day (Ref). Some patients may require up to 40 mg/day for optimal response (Ref); some experts suggest 3- to 4-week titration intervals (Ref).
Premenstrual dysphoric disorder: Note: Some experts prefer selective serotonin reuptake inhibitors (SSRIs) other than paroxetine for this use (Ref).
Continuous daily dosing regimen:
Immediate release (off-label): Oral: Initial: 10 mg once daily; increase to usual effective dose of 20 mg once daily over the first month; in a subsequent menstrual cycle, a further increase to 40 mg/day may be necessary in some patients for optimal response (Ref).
Extended release: Oral: Initial: 12.5 mg once daily; increase to usual effective dose of 25 mg once daily over the first month; in a subsequent menstrual cycle, a further increase to 50 mg/day (based on equivalent IR dose) may be necessary in some patients for optimal response (Ref).
Intermittent regimens:
Luteal phase dosing regimen:
Immediate release (off-label): Oral: Initial: 10 mg once daily during the luteal phase of menstrual cycle only (ie, beginning therapy 14 days before anticipated onset of menstruation and continued to the onset of menses); over the first month, may increase to usual effective dose of 20 mg once daily during the luteal phase; in a subsequent menstrual cycle, a further increase to 30 mg/day during the luteal phase may be necessary in some patients for optimal response (Ref).
Extended release: Oral: Initial: 12.5 mg once daily during the luteal phase of menstrual cycle only (ie, beginning therapy 14 days before anticipated onset of menstruation and continued to the onset of menses); over the first month, may increase to usual effective dose of 25 mg once daily during the luteal phase; in a subsequent menstrual cycle, a further increase to 37.5 mg/day (based on equivalent IR dose) during the luteal phase may be necessary in some patients for optimal response (Ref).
Symptom-onset dosing regimen (off-label): Immediate release: Oral: Initial: 10 mg once daily from the day of symptom onset until a few days after the start of menses; over the first month, may increase dose based on response and tolerability up to 20 mg/day; in a subsequent menstrual cycle, a further increase to 30 mg/day may be necessary in some patients for optimal response (Ref).
Social anxiety disorder:
Immediate release: Oral: Initial: 10 to 20 mg once daily; after 4 to 6 weeks at this dose, may increase dose based on response and tolerability in increments of 10 mg/day at intervals ≥1 week to a maximum of 60 mg/day (Ref).
Extended release: Oral: Initial: 12.5 to 25 mg once daily; after 4 to 6 weeks at this dose, may increase dose based on response and tolerability in increments of 12.5 mg/day at intervals ≥1 week up to a maximum of 37.5 mg/day (Ref). Note: Doses up to 75 mg/day (based on equivalent IR dose) may be necessary in some patients for optimal response (Ref).
Vasomotor symptoms associated with menopause (alternative agent): Note: Nonhormonal alternative for the management of vasomotor symptoms associated with menopause in patients with contraindications to hormonal therapy or who prefer not to use hormonal therapy (Ref).
Immediate release :
Capsule: Oral: 7.5 mg once daily at bedtime.
Tablet (off-label): Oral: 10 to 20 mg once daily at bedtime (Ref).
Extended release (off-label): Oral: 12.5 to 25 mg once daily at bedtime (Ref).
Dosing conversions: Immediate release 10 mg is equivalent to extended release 12.5 mg (Ref).
Discontinuation of therapy: Paroxetine is likely to cause discontinuation symptoms if stopped abruptly. When discontinuing treatment that has lasted for ≥4 weeks, gradually taper the dose (eg, over 3 to 4 weeks) to minimize withdrawal symptoms and detect reemerging symptoms (Ref). For brief treatment (eg, 2 to 3 weeks), may taper over 1 to 2 weeks; <2 weeks of treatment generally does not warrant taper (Ref). Reasons for a slower taper (eg, over ≥4 weeks) include prior history of antidepressant withdrawal symptoms or high doses of antidepressants (Ref). If intolerable withdrawal symptoms occur, resume the previously prescribed dose and/or decrease dose at a more gradual rate (Ref). Select patients (eg, those with a history of discontinuation syndrome) on long-term treatment (>6 months) may benefit from tapering over >3 months (Ref). Evidence supporting ideal taper rates is limited (Ref).
Switching antidepressants: Evidence for ideal antidepressant switching strategies is limited; strategies include cross-titration (gradually discontinuing the first antidepressant while at the same time gradually increasing the new antidepressant) and direct switch (abruptly discontinuing the first antidepressant and then starting the new antidepressant at an equivalent dose or lower dose and increasing it gradually). Cross-titration (eg, over 1 to 4 weeks depending upon sensitivity to discontinuation symptoms and adverse effects) is standard for most switches, but is contraindicated when switching to or from an MAOI. A direct switch may be an appropriate approach when switching to another agent in the same or similar class (eg, when switching between two SSRIs), when the antidepressant to be discontinued has been used for <1 week, or when the discontinuation is for adverse effects. When choosing the switch strategy, consider the risk of discontinuation symptoms, potential for drug interactions, other antidepressant properties (eg, half-life, adverse effects, pharmacodynamics), and the degree of symptom control desired (Ref).
Switching to or from an MAOI:
Allow 14 days to elapse between discontinuing an MAOI and initiation of paroxetine.
Allow 14 days to elapse between discontinuing paroxetine and initiation of an MAOI.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function:
CrCl >60 mL/minute: No dosage adjustment necessary (Ref).
CrCl 30 to 60 mL/minute: There are no dosage adjustments provided in manufacturer's labeling; however, AUCs after a single paroxetine dose were approximately 2 times that of individuals with normal function (Ref). Consider a 25% to 50% reduction in initial dose and titrate based on efficacy and tolerability, not to exceed the usual indication-specific maximum recommended dose (refer to dosing in adults) (Ref).
CrCl <30 mL/minute: AUCs after a single paroxetine dose were ~3.5 times that of patients with normal kidney function (Ref).
Immediate release: Initial: 5 to 10 mg/day; increase if needed by increments of no more than 10 mg/day at intervals of at least 1 week based on efficacy and tolerability; maximum dose: 40 mg/day or the indication-specific maximum recommended dose (refer to dosing in adults), whichever is less (Ref).
Extended release: Initial: 12.5 mg/day; increase if needed by 12.5 mg/day increments at intervals of at least 1 week based on efficacy and tolerability to a maximum dose of 50 mg/day or the indication-specific maximum recommended dose (refer to dosing in adults), whichever is less (Ref).
Hemodialysis, intermittent (thrice weekly): Not likely to be significantly dialyzable due to large Vd and high protein binding (Ref).
Oral: Dose for CrCl <30 mL/minute (Ref).
Peritoneal dialysis: Not likely to be significantly dialyzable due to large Vd and high protein binding (Ref).
Oral: Dose for CrCl <30 mL/minute (Ref).
CRRT:
Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) and minimal residual kidney function unless otherwise noted. Close monitoring of response and adverse reactions due to drug accumulation is important.
Oral: Dose as for CrCl <30 mL/minute (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration):
Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Close monitoring of response and adverse reactions due to drug accumulation is important.
Oral: Dose as for CrCl <30 mL/minute (Ref).
The liver dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Matt Harris, PharmD, MHS, BCPS, FAST; Jeong Park, PharmD, MS, BCTXP, FCCP, FAST; Arun Jesudian, MD; Sasan Sakiani, MD.
Note: Paroxetine is extensively metabolized by the liver to inactive metabolites, with a first-pass effect that can become saturated leading to nonlinear pharmacokinetics (Ref). In patients with cirrhosis, both half-life and exposure may be increased (Ref).
Liver impairment prior to treatment initiation:
Initial or dose titration in patients with preexisting liver cirrhosis:
Child-Turcotte-Pugh class A and B:
Immediate release: Oral: Initial: Use lowest recommended indication-specific dose; may titrate, if necessary, based on response and tolerability; use with caution (Ref).
Extended release: Oral: Initial: Use lowest recommended indication-specific dose; may titrate, if necessary, based on response and tolerability; use with caution (Ref).
Child-Turcotte-Pugh class C:
Immediate release: Oral: Initial: 10 mg/day; increase if needed by increments of no more than 10 mg/day at intervals of at least 1 week based on efficacy and tolerability; use with caution; maximum dose: 40 mg/day or the indication-specific maximum recommended dose, whichever is less (Ref).
Extended release: Oral: Initial: 12.5 mg/day; increase if needed by 12.5 mg/day increments at intervals of at least 1 week based on efficacy and tolerability; use with caution: maximum dose: 50 mg/day or the indication-specific maximum recommended dose, whichever is less (Ref).
Liver impairment developing in patients already receiving paroxetine:
Chronic disease progression (eg, outpatient):
Child-Turcotte-Pugh class A to C: Oral: No dosage adjustment necessary; use with caution (Ref).
Note: Avoid use (Ref).
Major depressive disorder (unipolar), obsessive-compulsive disorder, panic disorder, social anxiety disorder:
Immediate release: Oral: Initial: 10 mg/day; may increase dose based on response and tolerability in increments of 10 mg/day at intervals ≥1 week to a maximum of 40 mg/day.
Extended release: Oral: Initial: 12.5 mg/day; may increase dose based on response and tolerability in increments of 12.5 mg/day at intervals ≥1 week to a maximum of 37.5 mg/day (social anxiety disorder) or 50 mg/day (major depressive disorder, panic disorder).
Note: An adequate trial for assessment of effect in obsessive-compulsive disorder is considered to be ≥6 weeks at the maximum tolerated dose (Ref).
Dosing conversions: Refer to adult dosing.
Discontinuation of therapy: Refer to adult dosing.
Switching antidepressants: Refer to adult dosing.
(For additional information see "Paroxetine: Pediatric drug information")
Dosage guidance:
Dosage form information: Immediate-release paroxetine is available in two salts, hydrochloride (eg, Paxil) and mesylate (eg, Brisdelle, Pexeva); use extra precaution to ensure correct product selection. Paroxetine is available as immediate-release and extended-release formulations; both formulations are dosed once daily but are not interchangeable on a mg to mg basis; based on adult bioavailability data, immediate-release 10 mg is equivalent to extended-release 12.5 mg (Ref).
Major depressive disorder (unipolar): Limited data available:
Note: The use of paroxetine should be reserved for refractory cases when other options are ineffective or unacceptable/intolerable to the patient; therapy should not be initiated in a primary care setting; patients should be closely monitored for adverse effects (eg, suicidal thoughts/behaviors) (Ref). Therapy should be initiated at a low dose and titrated every 1 to 2 weeks based on response and tolerability (Ref).
Children ≥12 years and Adolescents: Oral: Immediate release (hydrochloride salt): Initial: 10 mg once daily; usual reported effective dose: 20 mg/day; maximum daily dose: 60 mg/day (Ref).
Obsessive-compulsive disorder (OCD): Limited data available:
Note: In the management of OCD in children and adolescents, if pharmacotherapy deemed necessary it should be in combination with cognitive behavioral therapy (CBT) and a selective serotonin reuptake inhibitor (SSRI) should be used first line; a preferred agent has not been identified (Ref).
Children ≥7 years and Adolescents <18 years: Oral: Immediate release (hydrochloride salt): Initial: 10 mg once daily; titrate every 7 to 14 days in 10 mg/day increments; mean reported effective dose: 32 mg/day; maximum daily dose: 60 mg/day (Ref).
Social anxiety disorder: Limited data available:
Note: In pediatric patients, selective serotonin reuptake inhibitor (SSRI) therapy is considered first-line pharmacologic treatment for moderate to severe anxiety disorders in combination with cognitive behavioral therapy (CBT); a preferred SSRI has not been defined; therapeutic selection should be based on pharmacokinetic and pharmacodynamic data, patient tolerability, cost, and unique risks/precautions with specific agents (Ref).
Children ≥8 years and Adolescents <18 years: Oral: Immediate release (hydrochloride salt): Initial: 10 mg once daily; titrate at intervals of at least 7 days in 10 mg/day increments; maximum daily dose: 50 mg/day. Dosing based on a 16-week multicenter, randomized, double-blind, placebo-controlled trial that reported the efficacy of paroxetine in pediatric patients (aged 8 to 17 years) with social anxiety disorder; 163 patients were randomized to receive paroxetine; the overall mean dose was 21.7 mg/day for children and 26.1 mg/day for adolescents (Ref).
Discontinuation of therapy: Consider planning discontinuation of therapy during lower-stress times, recognizing non-illness-related factors could cause stress or anxiety and be misattributed to OCD treatment discontinuation (Ref). To discontinue therapy, gradually taper the dose to minimize the incidence of discontinuation syndromes (withdrawal) and allow for the detection of reemerging disease state symptoms (eg, relapse). Evidence supporting ideal taper rates after illness remission is sparse, particularly in pediatric patients; however, a general consensus is to taper over several weeks to months and to resume the previous OCD therapy if symptoms worsen; a plan for continued psychotherapy during serotonergic medication discontinuation is recommended (Ref). A unified taper protocol has been reported in adults with OCD in which serotonin reuptake inhibitor monotherapy was tapered over 12 weeks with biweekly psychiatrist visits (Ref). For the treatment of depression, experts suggest tapering therapy over at least several weeks with consideration to the half-life of the antidepressant; agents with a shorter half-life may need to be tapered more conservatively and if intolerable discontinuation symptoms occur following a dose reduction, consider resuming the previously prescribed dose and/or decrease dose at a more gradual rate; similar principles may also be applicable to OCD therapy discontinuation (Ref).
Switching selective serotonin reuptake inhibitor (SSRI): Evidence for ideal SSRI switching strategies in pediatric patients is sparse; strategies described in pediatric guidelines include a conservative approach (tapering and discontinuing the first SSRI before adding the second) and cross-titration (gradually discontinuing the first antidepressant while at the same time gradually increasing the new antidepressant). While consensus does not exist regarding which approach to utilize, it is important to note that the conservative approach runs the risk for exacerbation of symptoms or discontinuation syndrome; cross-titration may avoid these risks (Ref). Cross-titration (eg, over 1 to 4 weeks depending upon sensitivity to discontinuation symptoms and adverse effects) is standard for most switches, but is contraindicated when switching to or from a monamine oxidase inhibitor. While not as common of a strategy, a direct switch may be considered when switching to another agent in the same or similar class (eg, when switching between 2 SSRIs), when the antidepressant to be discontinued has been used for <1 week, or when the discontinuation is for adverse effects. When choosing the switch strategy, consider the risk of discontinuation symptoms, potential for drug interactions, other antidepressant properties (eg, half-life, adverse effects, pharmacodynamics), and the degree of symptom control desired (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children ≥7 years and Adolescents: Oral: There are no pediatric-specific recommendations; based on pharmacokinetics in adult patients, plasma concentration is 2 times that seen in normal function in mild to moderate renal impairment (CrCl 30 to 60 mL/minute), and in severe impairment (CrCl <30 mL/minute) mean plasma concentration is ~4 times that seen in normal function; dosing adjustment suggested.
There are no pediatric-specific recommendations; based on pharmacokinetics in adult patients with hepatic dysfunction, plasma concentration is 2 times that seen in normal function; dosing adjustment suggested.
Antidepressants (when used as monotherapy) may precipitate a mixed/manic episode in patients with bipolar disorder. Treatment-emergent mania or hypomania in patients with unipolar major depressive disorder (MDD) have been reported, as many cases of bipolar disorder present in episodes of MDD (Ref). In addition, treatment-emergent mania or hypomania has been described in patients receiving antidepressants, including selective serotonin reuptake inhibitors, for the treatment of obsessive-compulsive disorder (OCD) without a history of bipolar disorder (with or without comorbid MDD) (Ref).
Mechanism: Non–dose-related; idiosyncratic. Unclear to what extent mood switches represent an uncovering of unrecognized bipolar disorder or a more direct pharmacologic effect independent of diagnosis (Ref).
Onset: Varied; a systematic review observed that the risk of switching increased significantly within the initial 2 years of antidepressant treatment in patients with unipolar MDD receiving an antidepressant as monotherapy, but not thereafter (up to 4.6 years) (Ref). In a systematic review of patients with OCD who experienced switching, the manic/hypomanic episodes were more common within 12 weeks of antidepressant treatment initiation; however, episodes occurred up to 9 months in these patients (Ref).
Risk factors:
• Family history of bipolar disorder (Ref)
• Depressive episode with psychotic symptoms (Ref)
• Younger age at onset of depression (Ref)
• Antidepressant resistance (Ref)
• Females (Ref)
Selective serotonin reuptake inhibitors (SSRIs) may increase the risk of bleeding, particularly if used concomitantly with antiplatelets and/or anticoagulants in adult and pediatric patients. Multiple observational studies have found an association with SSRI use and a variety of bleeding complications, ranging from bruising, hematoma, petechiae, purpuric disease, and epistaxis to cerebrovascular accident, upper GI bleeding (UGIB), intracranial hemorrhage, postpartum hemorrhage (exposure during late gestation), and intraoperative bleeding, although conflicting evidence also exists (Ref).
Mechanism: Possibly via decreased platelet serotonin concentrations and inhibition of serotonin-mediated platelet activation leading to subsequent platelet dysfunction (Ref). Paroxetine is considered to display high affinity for the serotonin reuptake receptor (Ref). SSRIs may also increase gastric acidity, which can increase the risk of GI bleeding (Ref).
Onset: Varied; bleeding risk is likely delayed for several weeks until SSRI-induced platelet serotonin depletion becomes clinically significant (Ref), although the onset of bleeding may be more unpredictable if patients are taking concomitant antiplatelets, anticoagulants, or nonsteroidal anti-inflammatory drugs (NSAIDs). For UGIB, some studies have found risk to be the highest in the first 28 to 30 days (Ref), whereas another study reported a median time of onset of 25 weeks (Ref).
Risk factors:
• Concomitant use of anticoagulants and/or antiplatelets (Ref)
• Preexisting platelet dysfunction or coagulation disorders (eg, von Willebrand factor) (Ref)
• Concomitant use of NSAIDs increases the risk for UGIB (Ref)
Limited data from observational studies involving mostly older adults (≥50 years of age) suggest selective serotonin reuptake inhibitors (SSRIs) are associated with an increased risk of bone fractures (Ref). In addition, several trials and subsequent meta-analyses have found an increased risk of bone fracture with the use of SSRIs in stroke survivors (Ref).
Mechanism: Time-related; mechanism not fully elucidated; postulated to be through a direct effect by SSRIs on bone metabolism via interaction with 5-HT and osteoblast, osteocyte, and/or osteoclast activity (Ref). SSRIs may also contribute to fall risk, contributing to the incidence of fractures (Ref). An increased tendency to fall may also contribute to the increased risk of fractures associated with SSRIs (Ref).
Onset: Delayed; risk appears to increase after initiation and may continue to increase with long-term use. A meta-analysis found risk of fracture increased from 2.9% over 1 year to 5.4% over 2 years; within 5 years, risk increased to 13.4% (Ref). Conversely, the increased risk of bone fracture in stroke survivors who received an SSRI (fluoxetine) was no longer statistically significant at 12 months post-stroke (Ref).
Risk factors:
• Long-term use may be a risk factor (Ref)
Paroxetine has been associated with a variety of hypersensitivity reactions, including severe systemic reactions; reactions include acute generalized exanthematous pustulosis (AGEP), toxic epidermal necrolysis (TEN), angioedema, vasculitis (eg, Henoch-Schönlein purpura, hypersensitivity angiitis), maculopapular rash, and certain pulmonary inflammatory diseases (eg, hypersensitivity pneumonitis) (Ref).
Mechanism: Non–dose-related; immunologic. Severe cutaneous adverse reactions, namely Stevens-Johnson syndrome/TEN, drug reaction with eosinophilia and systemic symptoms (DRESS), and AGEP, are delayed type IV hypersensitivity reactions involving a T-cell mediated drug-specific immune response (Ref).
Onset: Intermediate; in the majority of cases, onset of symptoms generally occurred from 1 to 2 weeks after initiation of therapy (Ref).
Risk factors:
• Females (Ref)
• Cross-reactivity between selective serotonin reuptake inhibitors has not been established, but has been reported between paroxetine and sertraline (Ref)
Selective serotonin reuptake inhibitors (SSRIs) are associated with syndrome of inappropriate antidiuretic hormone secretion (SIADH) and/or hyponatremia, including severe cases, predominantly in older adults (Ref). Hyponatremia is reversible with discontinuation of therapy (Ref).
Mechanism: May cause SIADH via release of antidiuretic hormone (ADH) (Ref) or may cause nephrogenic SIADH by increasing the sensitivity of the kidney to ADH (Ref).
Onset: Intermediate; usually develops within the first few weeks of treatment with an SSRI (Ref).
Risk factors:
• Older age (Ref)
• Females (Ref)
• Concomitant use of diuretics (Ref)
• Low body weight (Ref)
• Lower baseline serum sodium concentration (Ref)
• Volume depletion (Ref)
• History of hyponatremia (potential risk factor) (Ref)
• Symptoms of psychosis (potential risk factor) (Ref)
Selective serotonin reuptake inhibitors (SSRIs) are associated with acute angle-closure glaucoma (AACG) in case reports and a case-controlled study. AACG may cause symptoms including eye pain, changes in vision, swelling, and redness, which can rapidly lead to permanent blindness if not treated (Ref). In addition, SSRIs may be associated with an increased risk of cataract development (Ref).
Mechanism: AACG: Unclear; hypothesized SSRIs may increase the intraocular pressure via serotonergic effects on ciliary body muscle activation and pupil dilation (Ref).
Risk factors:
For AACG:
• Females (Ref)
• ≥50 years of age (slight increase) (Ref)
• Hyperopia (slight increase) (Ref)
• Personal or family history of AACG (Ref)
• Inuit or Asian descent (Ref)
Serotonin syndrome has been reported and typically occurs with coadministration of multiple serotonergic drugs. Only a handful of cases of serotonin syndrome have been reported with paroxetine monotherapy at therapeutic doses, in addition to a case which occurred following paroxetine overdose (Ref). The diagnosis of serotonin syndrome is made based on the Hunter Serotonin Toxicity Criteria (Ref) and may result in a spectrum of symptoms, such as anxiety, agitation, confusion, delirium, hyperreflexia, muscle rigidity, myoclonus, tachycardia, tachypnea, and tremor. Severe cases may cause hyperthermia, significant autonomic instability (ie, rapid and severe changes in blood pressure and pulse), coma, and seizures (Ref).
Mechanism: Dose-related; overstimulation of serotonin receptors by serotonergic agents (Ref).
Onset: Rapid; in the majority of cases (74%), onset occurred within 24 hours of treatment initiation, overdose, or change in dose (Ref).
Risk factors:
• Concomitant use of drugs that increase serotonin synthesis, block serotonin reuptake and/or impair serotonin metabolism (eg, monamine oxidase inhibitors [MAO inhibitors]). Of note, concomitant use of some serotonergic agents, such as MAO inhibitors, are contraindicated.
Selective serotonin reuptake inhibitors (SSRIs) are commonly associated with sexual disorders in both men and women. The following adverse reactions have been associated with SSRI use: Ejaculatory delay, orgasm disturbance, erectile dysfunction, and decreased libido (Ref). Priapism and decreased penile sensation have also been reported (Ref). The impact on sexual health may be lessened with drug holidays; in an open-label trial, patients taking an SSRI (other than fluoxetine) who were instructed to not take their medication on the weekends (n=63) reported improved erection, ejaculation, satisfaction, and overall sexual health without significant worsening in their mental health status (Ref).
Mechanism: Dose-related (Ref); increases in serotonin may affect other hormones and neurotransmitters involved in sexual function, in particular, testosterone's effect on sexual arousal and dopamine's role in achieving orgasm (Ref).
Risk factors:
• Depression (sexual dysfunction is commonly associated with depression; SSRI-associated sexual dysfunction may be difficult to differentiate in treated patients) (Ref)
Antidepressants are associated with an increased risk of suicidal ideation and suicidal tendencies in pediatric and young adult patients (18 to 24 years) in short-term studies. In adults >24 years, short-term studies did not show an increased risk of suicidal thinking and behavior and in older adults ≥65 years of age, a decreased risk was observed. Although data have yielded inconsistent results regarding the association of antidepressants and risk of suicide, particularly among adults, collective evidence shows a trend of an elevated risk of suicidality in younger age groups (Ref). Of note, the risk of a suicide attempt is inherent in major depression and may persist until remission occurs.
Mechanism: Not established; one of several postulated mechanisms is antidepressants may energize suicidal patients to act on impulses; another suggests that antidepressants may produce a worsening of depressive symptoms leading to the emergence of suicidal thoughts and actions (Ref).
Onset: Varied; increased risk observed in short-term studies (ie, <4 months) in pediatric and young adults; it is unknown whether this risk extends to long-term use (ie, >4 months).
Risk factors:
• Children and adolescents (Ref)
• Depression (risk of suicide associated with major depression and may persist until remission occurs)
Withdrawal syndrome, consisting of both somatic symptoms (eg, dizziness, chills, light-headedness, vertigo, shock-like sensations, paresthesia, fatigue, headache, nausea, tremor, diarrhea, visual disturbances) and psychological symptoms (eg, anxiety, agitation, confusion, insomnia, irritability), have been reported, primarily following abrupt discontinuation in adult and pediatric patients (Ref). Withdrawal symptoms may also occur following gradual tapering (Ref).
Mechanism: Withdrawal; due to reduced availability of serotonin in the CNS with decreasing levels of the selective serotonin reuptake inhibitor (SSRI). Other neurotransmission systems, including increased glutamine and dopamine, may also be affected, as well as the hypothalamic-pituitary-adrenal axis (Ref).
Onset: Intermediate; expected onset is 1 to 10 days (following either abrupt or tapered discontinuation) (Ref).
Risk factors:
• Abrupt discontinuation (rather than dose taper) or tapering the antidepressant too quickly (Ref)
• Drugs with a half-life <24 hours (eg, paroxetine, venlafaxine) (Ref)
• Higher doses (Ref)
• Longer duration of treatment (eg, ≥4 weeks) (Ref)
• Prior history of antidepressant withdrawal symptoms (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Dermatologic: Diaphoresis (5% to 14%)
Endocrine & metabolic: Decreased libido (≤15%) (table 1)
|
Drug (Paroxetine) |
Placebo |
Population |
Indication |
Number of Patients (Paroxetine) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|
|
0% to 9% |
0% to 2% |
Females |
Multiple trials in a variety of conditions: MDD, OCD, PD, social anxiety disorder, GAD, and PTSD |
1,822 |
1,340 |
Multiple placebo-controlled clinical trials evaluating different components of sexual dysfunction |
|
6% to 15% |
0% to 5% |
Males |
Multiple trials in a variety of conditions: MDD, OCD, PD, social anxiety disorder, GAD, and PTSD |
1,446 |
1,042 |
Multiple placebo-controlled clinical trials evaluating different components of sexual dysfunction |
Gastrointestinal: Constipation (2% to 16%), decreased appetite (1% to 12%), diarrhea (6% to 18%), dyspepsia (2% to 13%), nausea (17% to 26%), xerostomia (3% to 18%)
Genitourinary: Ejaculatory disorder (13% to 28%) (table 2)
|
Drug (Paroxetine) |
Placebo |
Indication |
Number of Patients (Paroxetine) |
Number of Patients (Placebo) |
|---|---|---|---|---|
|
13% to 28% |
0% to 2% |
Multiple trials in a variety of conditions: MDD, OCD, PD, social anxiety disorder, GAD, and PTSD |
1,446 |
1,042 |
Nervous system: Asthenia (12% to 22%), dizziness (6% to 14%), drowsiness (3% to 24%, less frequent in children and adolescents) (Ref), headache (6% to 27%, including vascular headache), insomnia (7% to 24%), tremor (4% to 11%)
1% to 10%:
Cardiovascular: Chest pain (3%), hypertension (≥1%), palpitations (2% to 3%), tachycardia (≥1%), vasodilation (2% to 4%)
Dermatologic: Pruritus (≥1%), skin rash (2% to 3%)
Endocrine & metabolic: Weight gain (≥1%)
Gastrointestinal: Abdominal pain (4% to 7%), dysgeusia (2%), flatulence (4% to 6%), increased appetite (2% to 4%), nausea and vomiting (4%), vomiting (2% to 3%; more frequent in children [two- to threefold] and adolescents) (Ref)
Genitourinary: Abnormal orgasm (2% to 9%) (table 3), difficulty in micturition (3%), dysmenorrhea (5%), erectile dysfunction (2% to 10%) (table 4), female genital tract disease (2% to 10%), male genital disease (10%), urinary frequency (2% to 3%), urinary tract infection (2%), urination disorder (3%)
|
Drug (Paroxetine) |
Placebo |
Population |
Indication |
Number of Patients (Paroxetine) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
2% to 9% |
0% to 1% |
Females |
Multiple trials in a variety of conditions: MDD, OCD, PD, social anxiety disorder, GAD, and PTSD |
1,822 |
1,340 |
|
Drug (Paroxetine) |
Placebo |
Dosage Form |
Indication |
Number of Patients (Paroxetine) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
2% to 9% |
0% to 3% |
Tablet |
Multiple trials in a variety of conditions: MDD, OCD, PD, social anxiety disorder, GAD, and PTSD |
1,446 |
1,042 |
|
5% to 10% |
0% to 3% |
Tablet, controlled release N/A |
Multiple trials in a variety of conditions: MDD, panic disorder, and social anxiety disorder |
328 |
369 |
Infection: Infection (5% to 6%)
Nervous system: Abnormal dreams (3% to 4%), agitation (3% to 5%), amnesia (2%), anxiety (2% to 5%), chills (2%), confusion (1%), depersonalization (3%), emotional lability (≥1%), fatigue (≤5%), hypomania (≤1%), intoxicated feeling (2%), lack of concentration (3% to 4%), lethargy (≤5%) malaise (≤5%), mania (≤1%), manic reaction (2%), myasthenia (1%), myoclonus (2% to 3%), nervousness (4% to 9%), paresthesia (4%), vertigo (≥1%), yawning (2% to 5%)
Neuromuscular & skeletal: Arthralgia (≥1%), back pain (3% to 5%), myalgia (2% to 5%), myopathy (2%)
Ophthalmic: Blurred vision (4%), visual disturbance (2% to 5%)
Otic: Tinnitus (≥1%)
Respiratory: Pharyngeal edema (2%), pharyngitis (4%), rhinitis (3%), sinusitis (4% to 8%)
<1%:
Cardiovascular: Acute myocardial infarction, angina pectoris, atrial fibrillation, atrioventricular nodal arrhythmia, bradycardia, bundle branch block, edema, heart block, heart failure, hypotension, ischemic heart disease, orthostatic hypotension, peripheral edema, phlebitis, premature ventricular contractions, pulmonary embolism, supraventricular extrasystole, syncope, thrombophlebitis, thrombosis
Dermatologic: Alopecia, dermal ulcer, ecchymoses, eczema, erythema multiforme, erythema nodosum, exfoliative dermatitis, maculopapular rash, skin discoloration, skin hypertrophy, skin photosensitivity, urticaria, vesicobullous dermatitis, xeroderma
Endocrine & metabolic: Adrenergic syndrome, amenorrhea, dehydration, diabetes mellitus, heavy menstrual bleeding, hirsutism, hypercalcemia, hypercholesterolemia, hyperglycemia, hyperkalemia, hyperphosphatemia, hyperthyroidism, hypocalcemia, hypoglycemia, hypokalemia, hyponatremia (literature suggests incidence of hyponatremia among SSRIs ranges from <1% to as high as 32%) (Ref), hypothyroidism, increased libido, increased thirst, ketosis, thyroiditis, weight loss
Gastrointestinal: Ageusia, aphthous stomatitis, bloody diarrhea, bruxism, cholelithiasis, colitis, dental bleeding (gums), duodenitis, dysphagia, enteritis, eructation, esophageal achalasia, esophagitis, fecal impaction, fecal incontinence, gastric ulcer, gastritis, gingivitis, glossitis, hematemesis, hiccups, ileitis, intestinal obstruction, melena, oral mucosal ulcer, oral paresthesia, peptic ulcer, peritonitis, rectal hemorrhage, sialadenitis, sialorrhea, stomatitis (including angular) (Ref), tongue discoloration
Genitourinary: Cystitis, dysuria, epididymitis, hematuria, lactation, leukorrhea, mastitis, nocturia, oliguria, polyuria, pyuria, urinary incontinence, urinary retention, urinary urgency, urolithiasis, uterine hemorrhage, vaginal hemorrhage
Hematologic & oncologic: Anemia (hypochromic, microcytic, normocytic, and iron deficiency), basophilia, eosinophilia, hematoma, hypergammaglobulinemia, leukocytosis, leukopenia, lymphadenopathy, lymphedema, monocytosis, prolonged bleeding time, purpuric disease, thrombocytopenia, thrombocytosis
Hepatic: Hepatic, hyperbilirubinemia, increased serum alanine aminotransferase, increased serum alkaline phosphatase, increased serum aspartate aminotransferase, jaundice
Hypersensitivity: Angioedema, facial edema, hypersensitivity reaction, tongue edema
Nervous system: Abnormal gait, akathisia, akinesia, altered sense of smell, antisocial behavior, aphasia, ataxia, bulimia nervosa, cerebral ischemia, cerebrovascular accident, choreoathetosis, delirium, delusion, depression with psychosis, drug dependence, dysarthria, euphoria, extrapyramidal reaction, hallucination, hostility, hyperacusis, hyperalgesia, hyperesthesia, hyperreflexia, hypertonia, hyporeflexia, hysteria, lack of emotion, manic depressive reaction, migraine, neuralgia, neuropathy, neurosis, paralysis, paranoid ideation, peripheral neuritis, psychosis, seizure, stupor, suicidal ideation, suicidal tendencies, trismus
Neuromuscular & skeletal: Arthritis, bursitis, dyskinesia, dystonia, fasciculations, gout, hypokinesia, muscle spasm, myelitis, myositis, osteoarthritis, osteoporosis, tenosynovitis, tetany, torticollis
Ophthalmic: Accommodation disturbance, amblyopia, anisocoria, blepharitis, blepharoptosis, cataract, conjunctival edema, corneal ulcer, diplopia, exophthalmos, keratoconjunctivitis, mydriasis, night blindness, nystagmus disorder, photophobia, retinal hemorrhage, visual field defect
Otic: Deafness
Renal: Increased blood urea nitrogen, nephritis, nephrolithiasis
Respiratory: Asthma, bronchitis, dyspnea, epistaxis, hemoptysis, pneumonia, pulmonary edema, pulmonary emphysema, pulmonary fibrosis, stridor
Postmarketing:
Cardiovascular: Torsades de pointes (Ref), vasculitis (Ref), ventricular fibrillation (Ref), ventricular tachycardia
Dermatologic: Acute generalized exanthematous pustulosis (Ref), hyperhidrosis, Stevens-Johnson syndrome, toxic epidermal necrolysis (Ref)
Endocrine & metabolic: Galactorrhea not associated with childbirth (Ref), hyperprolactinemia (Ref), porphyria, SIADH (Ref), uncontrolled diabetes mellitus
Gastrointestinal: Acute pancreatitis, hemorrhagic pancreatitis
Genitourinary: Preeclampsia, priapism (Ref), sexual disorder (Ref)
Hematologic & oncologic: Agranulocytosis, aplastic anemia, bone marrow aplasia, hemolytic anemia, Henoch-Schönlein purpura, immune thrombocytopenia, pancytopenia
Hepatic: Hepatic failure, hepatic necrosis, hepatotoxicity (Ref)
Hypersensitivity: Anaphylaxis, drug reaction with eosinophilia and systemic symptoms, nonimmune anaphylaxis
Nervous system: Aggressive behavior (Ref), anosmia (including hyposmia), cogwheel rigidity, disorientation (Ref), Guillain-Barré syndrome, homicidal ideation (Ref), hyperactive behavior (including hyperkinetic muscle activity; more frequent in children [two- to threefold] and adolescents) (Ref), intracranial hemorrhage (Ref), neuroleptic malignant syndrome (with drug interactions) (Ref), restless leg syndrome (Ref), restlessness (Ref), serotonin syndrome (Ref), status epilepticus (Ref), withdrawal syndrome (Ref)
Neuromuscular & skeletal: Bradykinesia
Ophthalmic: Acute angle-closure glaucoma (Ref), optic neuritis
Renal: Acute kidney injury
Respiratory: Hypersensitivity pneumonitis (Ref), laryngismus, pulmonary alveolitis (allergic), pulmonary hypertension
Hypersensitivity (eg, anaphylaxis, angioedema, Stevens-Johnson syndrome) to paroxetine or any component of the formulation; concurrent use with or within 14 days of monoamine oxidase inhibitors (MAOIs) (including linezolid and IV methylene blue); concomitant use with pimozide or thioridazine (risk of QT prolongation); pregnancy (Brisdelle only).
Note: Although paroxetine is contraindicated per the manufacturer labeling when used in combination with linezolid, new evidence suggests that the combination is unlikely to cause serotonin syndrome (0.06% to 3% risk), and therefore these agents can be administered concomitantly when necessary. Monitor patients on this combination; average duration of serotonin toxicity is ~4 days; however, risks may be greater with longer durations of concurrent therapy. Educate patients on the signs and symptoms of serotonin syndrome (Bai 2022; Butterfield 2012; Karkow 2017; Kufel 2023; Narita 2007; Taylor 2006a).
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in US labeling): Initiation of paroxetine within 2 weeks of pimozide or thioridazine discontinuation.
Concerns related to adverse effects:
• Akathisia: Inability to remain still due to feelings of agitation or restlessness has been observed with paroxetine and other selective serotonin reuptake inhibitors (SSRIs). Usually occurs within the first few weeks of therapy.
• Anticholinergic effects: Has low potential for sedation and anticholinergic effects relative to cyclic antidepressants; however, among the SSRI class these effects are relatively higher.
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).
Disease-related concerns:
• Bariatric surgery: Presurgical assessment of the indication for use, symptoms, and goals of therapy should be documented to enable postsurgical assessment. A single case report and an in vitro study suggest paroxetine exposure is altered post bariatric surgery (Bingham 2014; Seaman 2005). Monitor for continued efficacy after bariatric surgery and consider switching to an alternate medication if symptoms worsen or side effects present.
• Cardiovascular disease: Use with caution in patients with cardiovascular disease; cases of QT interval prolongation have been reported (causality has not been established). Use with caution in patients with a history of QT interval prolongation, taking antiarrhythmic medications, or taking other medications that may potentially prolong QT interval.
• Hepatic impairment: Use with caution in patients with hepatic impairment; clearance is decreased and plasma concentrations are increased; a lower dosage may be needed. However, selective serotonin reuptake inhibitors such as paroxetine are considered the safest antidepressants to use in chronic liver disease because of their relative lack of side effects and high therapeutic index (Mullish 2014).
• Renal impairment: Use with caution in patients with renal impairment; clearance is decreased and plasma concentrations are increased; a lower dosage may be needed.
• Seizure disorder: Use with caution in patients with seizure disorder.
Dosage form specific issues:
• Brisdelle: Brisdelle contains a lower dose than what is required for the treatment of major depressive disorder and psychiatric conditions. Patients who require paroxetine for the treatment of psychiatric conditions should discontinue Brisdelle and begin treatment with a paroxetine-containing medication which provides an adequate dosage.
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley, 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
Some dosage forms may contain propylene glycol; in neonates, large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).
Pexeva has been discontinued in the United States for >1 year.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral, as mesylate [strength expressed as base]:
Brisdelle: 7.5 mg [DSC] [contains fd&c red #40 (allura red ac dye), fd&c yellow #6 (sunset yellow)]
Generic: 7.5 mg
Suspension, Oral, as hydrochloride [strength expressed as base]:
Paxil: 10 mg/5 mL (250 mL) [contains fd&c yellow #6(sunset yellow)alumin lake, methylparaben, propylene glycol, propylparaben, saccharin sodium; orange flavor]
Generic: 10 mg/5 mL (250 mL)
Tablet, Oral, as hydrochloride [strength expressed as base]:
Paxil: 10 mg, 20 mg [scored; contains fd&c blue #2 (indigo carm) aluminum lake, fd&c yellow #6(sunset yellow)alumin lake, quinoline (d&c yellow #10) aluminum lake]
Paxil: 30 mg [contains fd&c blue #2 (indigo carm) aluminum lake, fd&c yellow #6(sunset yellow)alumin lake, quinoline (d&c yellow #10) aluminum lake]
Paxil: 40 mg [DSC]
Paxil: 40 mg [contains fd&c blue #2 (indigo carm) aluminum lake, fd&c yellow #6(sunset yellow)alumin lake, quinoline (d&c yellow #10) aluminum lake]
Generic: 10 mg, 20 mg, 30 mg, 40 mg
Tablet, Oral, as mesylate [strength expressed as base]:
Pexeva: 10 mg [DSC], 20 mg [DSC], 30 mg [DSC], 40 mg [DSC]
Tablet Extended Release 24 Hour, Oral, as hydrochloride [strength expressed as base]:
Paxil CR: 12.5 mg [contains fd&c yellow #6(sunset yellow)alumin lake, quinoline (d&c yellow #10) aluminum lake]
Paxil CR: 25 mg [DSC]
Paxil CR: 25 mg [contains fd&c blue #2 (indigo carm) aluminum lake, fd&c yellow #6(sunset yellow)alumin lake, quinoline (d&c yellow #10) aluminum lake]
Paxil CR: 37.5 mg [DSC] [contains fd&c blue #2 (indigo carm) aluminum lake]
Paxil CR: 37.5 mg [contains fd&c blue #2 (indigo carm) aluminum lake, fd&c yellow #6(sunset yellow)alumin lake, quinoline (d&c yellow #10) aluminum lake]
Generic: 12.5 mg, 25 mg, 37.5 mg
Yes
Capsules (PARoxetine Mesylate Oral)
7.5 mg (per each): $6.60
Suspension (PARoxetine HCl Oral)
10 mg/5 mL (per mL): $1.58
Suspension (Paxil Oral)
10 mg/5 mL (per mL): $2.13
Tablet, 24-hour (PARoxetine HCl ER Oral)
12.5 mg (per each): $0.80 - $5.58
25 mg (per each): $0.86 - $5.82
37.5 mg (per each): $0.92 - $5.99
Tablet, 24-hour (Paxil CR Oral)
12.5 mg (per each): $12.13
25 mg (per each): $12.66
37.5 mg (per each): $13.04
Tablets (PARoxetine HCl Oral)
10 mg (per each): $1.95 - $2.67
20 mg (per each): $2.29 - $2.73
30 mg (per each): $2.70 - $2.83
40 mg (per each): $2.88 - $3.18
Tablets (Paxil Oral)
10 mg (per each): $11.78
20 mg (per each): $12.29
30 mg (per each): $12.66
40 mg (per each): $13.38
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral, as hydrochloride [strength expressed as base]:
Paxil: 10 mg [DSC], 20 mg, 30 mg [contains polysorbate 80]
Generic: 10 mg, 20 mg, 30 mg
Tablet Extended Release 24 Hour, Oral, as hydrochloride [strength expressed as base]:
Paxil CR: 12.5 mg [contains fd&c yellow #6(sunset yellow)alumin lake, polysorbate 80, quinoline (d&c yellow #10) aluminum lake]
Paxil CR: 25 mg [contains polysorbate 80]
Oral: May be administered without regard to meals. Administer preferably in the morning; when used for vasomotor symptoms of menopause, administer at bedtime. Do not crush, break, or chew ER or IR film-coated tablets. Shake suspension well before use.
Bariatric surgery: Paroxetine is available in an ER formulation and the release characteristics may be significantly altered in an unknown manner in patients who have undergone bariatric surgery; providers should determine if the condition being treated can be safely monitored or if a switch to an alternate formulation is necessary (Ref). Paroxetine is also available in IR formulations. Available oral suspensions may contain nonabsorbable sugars (eg, mannitol, sorbitol, xylitol) that can cause dumping syndrome after bariatric surgery; refer to product labeling and monitor for tolerability with use (Ref).
Oral: May be administered without regard to meals; administration with food may decrease GI side effects; shake suspension well before use. Paxil should preferentially be administered in the morning. Do not chew or crush immediate- or controlled-release tablet; swallow whole.
Hazardous agent (NIOSH 2024 [table 2]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Brisdelle: https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/204516s009s014lbl.pdf#page=22
Paxil: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/020031s083,020710s051lbl.pdf#page=39
Paxil CR: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/020936s057s064lbl.pdf
Pexeva: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/021299s035s038lbl.pdf#page=18
Generalized anxiety disorder (immediate release): Treatment of generalized anxiety disorder.
Major depressive disorder (unipolar) (immediate and extended release): Treatment of unipolar major depressive disorder.
Obsessive-compulsive disorder (immediate release): Treatment of obsessions and compulsions in patients with obsessive-compulsive disorder.
Panic disorder (immediate and extended release): Treatment of panic disorder, with or without agoraphobia.
Posttraumatic stress disorder (immediate release): Treatment of posttraumatic stress disorder.
Premenstrual dysphoric disorder (extended release): Treatment of premenstrual dysphoric disorder.
Social anxiety disorder (immediate and extended release): Treatment of social anxiety disorder, also known as social phobia.
Vasomotor symptoms of menopause (immediate release; 7.5 mg capsule): Treatment of moderate to severe vasomotor symptoms associated with menopause.
Body dysmorphic disorder; Premature ejaculation
PARoxetine may be confused with DULoxetine, FLUoxetine, PACLitaxel, piroxicam, pyridoxine, vortioxetine
Paxil may be confused with Doxil, PACLitaxel, Plavix, PROzac, Taxol, Trexall
Pexeva [DSC] may be confused with Lexiva
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs (contraindicated in pregnancy [Brisdelle]) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Community/Ambulatory Care Settings).
Beers Criteria: Paroxetine is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older (independent of diagnosis or condition) due to its strong anticholinergic properties and potential for sedation and orthostatic hypotension. In addition, use the SSRIs with caution due to their potential to cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatremia; monitor sodium closely with initiation or dosage adjustments in older adults (Beers Criteria [AGS 2023]).
Paroxetine is identified in the Screening Tool of Older Person's Prescriptions (STOPP) criteria as a potentially inappropriate medication in older adults (≥65 years of age) with a history of recurrent falls due to an increased risk of falls. In addition, some disease states of concern include hyponatremia and recent or current significant bleeding (O’Mahony 2023).
Substrate of CYP2D6 (Major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2D6 (Strong);
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Abciximab: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Abrocitinib: Agents with Antiplatelet Effects may increase antiplatelet effects of Abrocitinib. Risk X: Avoid
Acalabrutinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Agents with Blood Glucose Lowering Effects: Selective Serotonin Reuptake Inhibitor may increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor
Ajmaline: CYP2D6 Inhibitors (Strong) may increase serum concentration of Ajmaline. Risk C: Monitor
Ajmaline: May increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor
Alcohol (Ethyl): May increase adverse/toxic effects of Selective Serotonin Reuptake Inhibitor. Specifically, the risk of psychomotor impairment may be enhanced. Management: Patients receiving selective serotonin reuptake inhibitors should be advised to avoid alcohol. Monitor for increased psychomotor impairment in patients who consume alcohol during treatment with selective serotonin reuptake inhibitors. Risk D: Consider Therapy Modification
Almotriptan: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Alosetron: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Amphetamines: May increase serotonergic effects of Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors). This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may increase serum concentration of Amphetamines. Management: Monitor for amphetamine toxicities, including serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability). Initiate amphetamines at lower doses, monitor frequently, and adjust dose as needed. Risk C: Monitor
Anagrelide: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Anticoagulants (Miscellaneous Agents): Antidepressants with Antiplatelet Effects may increase anticoagulant effects of Anticoagulants (Miscellaneous Agents). Risk C: Monitor
Antiemetics (5HT3 Antagonists): May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Antiplatelet Agents (P2Y12 Inhibitors): Agents with Antiplatelet Effects may increase antiplatelet effects of Antiplatelet Agents (P2Y12 Inhibitors). Risk C: Monitor
Antipsychotic Agents: Serotonergic Agents (High Risk) may increase adverse/toxic effects of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor
ARIPiprazole Lauroxil: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of ARIPiprazole Lauroxil. Management: Decrease aripiprazole lauroxil dose to next lower strength if used with strong CYP2D6 inhibitors for over 14 days. No dose adjustment needed if using the lowest dose (441 mg) or if a CYP2D6 PM. Max dose is 441 mg if also taking strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification
ARIPiprazole: CYP2D6 Inhibitors (Strong) may increase serum concentration of ARIPiprazole. Management: Aripiprazole dose reductions or avoidance are required for indications other than major depressive disorder. Dose adjustments vary based on formulation, initial starting dose, and the additional use of CYP3A4 inhibitors. See interact monograph for details Risk D: Consider Therapy Modification
Artemether and Lumefantrine: May increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor
Asenapine: May increase serum concentration of PARoxetine. Management: Decrease the paroxetine dose by half when used concomitantly with asenapine. Monitor patients receiving this combination closely for signs and symptoms of increased paroxetine toxicity. Risk D: Consider Therapy Modification
Aspirin: Selective Serotonin Reuptake Inhibitor may increase antiplatelet effects of Aspirin. Risk C: Monitor
Atomoxetine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Atomoxetine. Management: Initiate atomoxetine at a reduced dose (patients who weigh up to 70 kg: 0.5 mg/kg/day; adults or patients who weigh 70 kg or more: 40 mg/day) in patients receiving a strong CYP2D6 inhibitor. Increase to usual target dose after 4 weeks if needed. Risk D: Consider Therapy Modification
Brexanolone: Selective Serotonin Reuptake Inhibitor may increase CNS depressant effects of Brexanolone. Risk C: Monitor
Brexpiprazole: CYP2D6 Inhibitors (Strong) may increase serum concentration of Brexpiprazole. Management: Reduce brexpiprazole dose to 50% of usual with strong CYP2D6 inhibitors, reduce to 25% of usual if used with both a strong CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor; these recommendations do not apply if treating major depressive disorder Risk D: Consider Therapy Modification
Bromopride: May increase adverse/toxic effects of Selective Serotonin Reuptake Inhibitor. Risk X: Avoid
Broom: CYP2D6 Inhibitors (Strong) may increase serum concentration of Broom. Specifically, the concentrations of sparteine, a constituent of broom, may be increased. Risk C: Monitor
BuPROPion: May increase adverse/toxic effects of PARoxetine. Risk C: Monitor
BusPIRone: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Caplacizumab: Agents with Antiplatelet Effects may increase adverse/toxic effects of Caplacizumab. Specifically, the risk of bleeding may be increased. Risk C: Monitor
Carvedilol: CYP2D6 Inhibitors (Strong) may increase serum concentration of Carvedilol. Risk C: Monitor
Chlorpheniramine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Chlorpheniramine. Risk C: Monitor
Cimetidine: May increase serum concentration of PARoxetine. Risk C: Monitor
Citalopram: May increase serotonergic effects of Selective Serotonin Reuptake Inhibitor. This could result in serotonin syndrome. Citalopram may increase antiplatelet effects of Selective Serotonin Reuptake Inhibitor. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, mental status changes) when these agents are combined. In addition, monitor for signs and symptoms of bleeding. Risk C: Monitor
CloZAPine: CYP2D6 Inhibitors (Strong) may increase serum concentration of CloZAPine. Risk C: Monitor
Collagenase (Systemic): Agents with Antiplatelet Effects may increase adverse/toxic effects of Collagenase (Systemic). Specifically, the risk of injection site bruising and or bleeding may be increased. Risk C: Monitor
Cyclobenzaprine: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
CYP2D6 Inhibitors (Moderate): May increase serum concentration of PARoxetine. Risk C: Monitor
CYP2D6 Inhibitors (Strong): May increase serum concentration of PARoxetine. Risk C: Monitor
Cyproheptadine: May decrease therapeutic effects of Selective Serotonin Reuptake Inhibitor. Risk C: Monitor
Dapoxetine: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Do not use serotonergic agents (high risk) with dapoxetine or within 7 days of serotonergic agent discontinuation. Do not use dapoxetine within 14 days of monoamine oxidase inhibitor use. Dapoxetine labeling lists this combination as contraindicated. Risk X: Avoid
Darunavir: May decrease serum concentration of PARoxetine. Risk C: Monitor
Dasatinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Deoxycholic Acid: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Desmopressin: Hyponatremia-Associated Agents may increase hyponatremic effects of Desmopressin. Risk C: Monitor
Deutetrabenazine: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Deutetrabenazine. Management: The total daily dose of deutetrabenazine should not exceed 36 mg with concurrent use of a strong CYP2D6 inhibitor. Risk D: Consider Therapy Modification
Dexmethylphenidate-Methylphenidate: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Dextromethorphan: May increase serotonergic effects of Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors). This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may increase serum concentration of Dextromethorphan. Management: Consider alternatives to this drug combination. The dose of dextromethorphan/bupropion product should not exceed 1 tablet once daily. Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity. Risk D: Consider Therapy Modification
Direct Oral Anticoagulants (DOACs): Antidepressants with Antiplatelet Effects may increase anticoagulant effects of Direct Oral Anticoagulants (DOACs). Risk C: Monitor
DOXOrubicin (Conventional): CYP2D6 Inhibitors (Strong) may increase serum concentration of DOXOrubicin (Conventional). Risk X: Avoid
DULoxetine: May increase serotonergic effects of Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors). This could result in serotonin syndrome. DULoxetine may increase antiplatelet effects of Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors). Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may increase serum concentration of DULoxetine. Management: Monitor for increased duloxetine effects/toxicities and signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperthermia, tremor, mental status changes) when these agents are combined. In addition, monitor for signs and symptoms of bleeding. Risk C: Monitor
Eletriptan: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Eliglustat: CYP2D6 Inhibitors (Strong) may increase serum concentration of Eliglustat. Management: Eliglustat dose is 84 mg daily with CYP2D6 inhibitors. Use is contraindicated (COI) when also combined with strong CYP3A4 inhibitors. When also combined with a moderate CYP3A4 inhibitor, use is COI in CYP2D6 EMs or IMs and should be avoided in CYP2D6 PMs. Risk D: Consider Therapy Modification
Epinephrine (Racemic): Selective Serotonin Reuptake Inhibitor may increase adverse/toxic effects of Epinephrine (Racemic). Risk X: Avoid
Ergot Derivatives: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Fenfluramine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Fenfluramine. Management: Limit fenfluramine dose to 20 mg/day without concurrent stiripentol or to 17 mg/day with concomitant stiripentol and clobazam when used with a strong CYP2D6 inhibitor. Risk D: Consider Therapy Modification
Fesoterodine: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Fesoterodine. Risk C: Monitor
Flecainide: CYP2D6 Inhibitors (Strong) may increase serum concentration of Flecainide. Risk C: Monitor
FLUoxetine: May increase serotonergic effects of PARoxetine. This could result in serotonin syndrome. FLUoxetine may increase antiplatelet effects of PARoxetine. FLUoxetine may increase serum concentration of PARoxetine. PARoxetine may increase serum concentration of FLUoxetine. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, mental status changes), bleeding, and increased SSRI toxicities when these agents are combined. Risk C: Monitor
FluPHENAZine: CYP2D6 Inhibitors (Strong) may increase serum concentration of FluPHENAZine. Risk C: Monitor
Fondaparinux: Antidepressants with Antiplatelet Effects may increase anticoagulant effects of Fondaparinux. Risk C: Monitor
Fosamprenavir: May decrease serum concentration of PARoxetine. The active metabolite amprenavir is likely responsible for this effect. Risk C: Monitor
Gefitinib: CYP2D6 Inhibitors (Strong) may increase serum concentration of Gefitinib. Risk C: Monitor
Gepirone: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor
Gilteritinib: May decrease therapeutic effects of Selective Serotonin Reuptake Inhibitor. Management: Avoid use of this combination if possible. If the combination cannot be avoided, monitor closely for evidence of reduced response to the selective serotonin reuptake inhibitor. Risk D: Consider Therapy Modification
Glycoprotein IIb/IIIa Inhibitors: Agents with Antiplatelet Effects may increase antiplatelet effects of Glycoprotein IIb/IIIa Inhibitors. Risk C: Monitor
Haloperidol: CYP2D6 Inhibitors (Strong) may increase serum concentration of Haloperidol. Risk C: Monitor
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may increase QTc-prolonging effects of Haloperidol. Risk C: Monitor
Heparin: Antidepressants with Antiplatelet Effects may increase anticoagulant effects of Heparin. Risk C: Monitor
Heparins (Low Molecular Weight): Antidepressants with Antiplatelet Effects may increase anticoagulant effects of Heparins (Low Molecular Weight). Risk C: Monitor
Herbal Products with Anticoagulant/Antiplatelet Effects: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Iboga: CYP2D6 Inhibitors (Strong) may increase serum concentration of Iboga. Risk C: Monitor
Ibritumomab Tiuxetan: Agents with Antiplatelet Effects may increase antiplatelet effects of Ibritumomab Tiuxetan. Risk C: Monitor
Ibrutinib: Agents with Antiplatelet Effects may increase adverse/toxic effects of Ibrutinib. Specifically, the risk of bleeding and hemorrhage may be increased. Risk C: Monitor
Iloperidone: CYP2D6 Inhibitors (Strong) may increase serum concentration of Iloperidone. CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Iloperidone. Specifically, concentrations of the metabolite P88 may be increased. CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of Iloperidone. Specifically, concentrations of the metabolite P95 may be decreased. Management: Reduce iloperidone dose by half when administered with a strong CYP2D6 inhibitor and monitor for increased iloperidone toxicities, including QTc interval prolongation and arrhythmias. Risk D: Consider Therapy Modification
Indoramin: CYP2D6 Inhibitors (Strong) may increase serum concentration of Indoramin. Risk C: Monitor
Inotersen: Agents with Antiplatelet Effects may increase adverse/toxic effects of Inotersen. Specifically, the risk of bleeding may be increased. Risk C: Monitor
Ioflupane I 123: Coadministration of Selective Serotonin Reuptake Inhibitor and Ioflupane I 123 may alter diagnostic results. Risk C: Monitor
Lasmiditan: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Levomethadone: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Limaprost: May increase adverse/toxic effects of Agents with Antiplatelet Effects. Specifically, the risk of bleeding may be increased. Risk C: Monitor
Linezolid: May increase serotonergic effects of Selective Serotonin Reuptake Inhibitor. This could result in serotonin syndrome. Risk X: Avoid
Lofexidine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Lofexidine. Risk C: Monitor
Maprotiline: CYP2D6 Inhibitors (Strong) may increase serum concentration of Maprotiline. Risk C: Monitor
Mavorixafor: May increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk X: Avoid
Mequitazine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Mequitazine. Risk X: Avoid
Metaxalone: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Methadone: CYP2D6 Inhibitors (Strong) may increase serum concentration of Methadone. Risk C: Monitor
Methadone: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Methylene Blue: Selective Serotonin Reuptake Inhibitor may increase serotonergic effects of Methylene Blue. This could result in serotonin syndrome. Risk X: Avoid
Metoclopramide: CYP2D6 Inhibitors (Strong) may increase serum concentration of Metoclopramide. Management: For gastroparesis: reduce metoclopramide dose to 5mg 4 times/day and limit to 20mg/day; nasal spray not recommended. For GERD: reduce metoclopramide dose to 5mg 4 times/day or to 10mg 3 times/day and limit to 30mg/day. Monitor for toxicity when combined. Risk D: Consider Therapy Modification
Metoprolol: CYP2D6 Inhibitors (Strong) may increase serum concentration of Metoprolol. Risk C: Monitor
Mexiletine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Mexiletine. Risk C: Monitor
Miscellaneous Antiplatelets: Agents with Antiplatelet Effects may increase antiplatelet effects of Miscellaneous Antiplatelets. Risk C: Monitor
Mivacurium: Selective Serotonin Reuptake Inhibitor may increase serum concentration of Mivacurium. Risk C: Monitor
Monoamine Oxidase Inhibitors (Antidepressant): Selective Serotonin Reuptake Inhibitor may increase serotonergic effects of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Risk X: Avoid
Nebivolol: CYP2D6 Inhibitors (Strong) may increase serum concentration of Nebivolol. Risk C: Monitor
Nefazodone: May increase serotonergic effects of Selective Serotonin Reuptake Inhibitor. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Nicergoline: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Nicergoline. Specifically, concentrations of the MMDL metabolite may be increased. CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of Nicergoline. Specifically, concentrations of the MDL metabolite may be decreased. Risk C: Monitor
Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): Selective Serotonin Reuptake Inhibitor may increase antiplatelet effects of Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective). Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective) may decrease therapeutic effects of Selective Serotonin Reuptake Inhibitor. Risk C: Monitor
Nonsteroidal Anti-Inflammatory Agents (Nonselective): Selective Serotonin Reuptake Inhibitor may increase antiplatelet effects of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Nonsteroidal Anti-Inflammatory Agents (Nonselective) may decrease therapeutic effects of Selective Serotonin Reuptake Inhibitor. Management: Consider alternatives to NSAIDs. Monitor for evidence of bleeding and diminished antidepressant effects. It is unclear whether COX-2-selective NSAIDs reduce risk. Risk D: Consider Therapy Modification
Nonsteroidal Anti-Inflammatory Agents (Topical): May increase antiplatelet effects of Selective Serotonin Reuptake Inhibitor. Risk C: Monitor
Obinutuzumab: Agents with Antiplatelet Effects may increase adverse/toxic effects of Obinutuzumab. Specifically, the risk of bleeding may be increased. Management: Consider avoiding coadministration of obinutuzumab and agents with antiplatelet effects, especially during the first cycle of obinutuzumab therapy. Risk D: Consider Therapy Modification
Oliceridine: May increase serotonergic effects of Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors). This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may increase serum concentration of Oliceridine. Management: Monitor for increased opioid effects (eg, respiratory depression, sedation) and for serotonin syndrome/serotonin toxicity when these agents are combined. Risk C: Monitor
Olmutinib: CYP2D6 Inhibitors (Strong) may increase serum concentration of Olmutinib. Risk C: Monitor
Ondansetron: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Opioid Agonists (metabolized by CYP3A4 and CYP2D6): May increase serotonergic effects of Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors). This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may decrease therapeutic effects of Opioid Agonists (metabolized by CYP3A4 and CYP2D6). Management: Monitor for decreased therapeutic response (eg, analgesia) and opioid withdrawal when coadministered with SSRIs that strongly inhibit CYP2D6. Additionally, monitor for serotonin syndrome/serotonin toxicity if these drugs are combined. Risk C: Monitor
Opioid Agonists (metabolized by CYP3A4): May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Opioid Agonists: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Opipramol: May increase serotonergic effects of Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors). This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may increase serum concentration of Opipramol. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased opipramol adverse effects when these agents are combined. Risk C: Monitor
Oxitriptan: Serotonergic Agents (High Risk) may increase serotonergic effects of Oxitriptan. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
OxyCODONE: May increase serotonergic effects of Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors). This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may increase serum concentration of OxyCODONE. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may decrease active metabolite exposure of OxyCODONE. Specifically, oxymorphone concentrations may be reduced. Risk C: Monitor
Peginterferon Alfa-2b: May decrease serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor
Pentosan Polysulfate Sodium: Agents with Antiplatelet Effects may increase adverse/toxic effects of Pentosan Polysulfate Sodium. Specifically, the risk of hemorrhage may be increased. Risk C: Monitor
Perhexiline: PARoxetine may increase serum concentration of Perhexiline. Perhexiline may increase serum concentration of PARoxetine. Risk C: Monitor
Perphenazine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Perphenazine. Risk C: Monitor
Pimozide: CYP2D6 Inhibitors (Strong) may increase serum concentration of Pimozide. Risk X: Avoid
Pirtobrutinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Pitolisant: CYP2D6 Inhibitors (Strong) may increase serum concentration of Pitolisant. Management: Reduce the pitolisant dose by 50% if a strong CYP2D6 inhibitor is initiated. For patients already receiving strong CYP2D6 inhibitors, initial doses of pitolisant should be reduced and depends on age and patient weight. See full monograph for details. Risk D: Consider Therapy Modification
Pravastatin: May increase adverse/toxic effects of PARoxetine. Specifically, blood glucose elevations may occur with the combination. Risk C: Monitor
Primaquine: CYP2D6 Inhibitors (Strong) may decrease therapeutic effects of Primaquine. CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of Primaquine. Management: Consider alternatives to the combination of primaquine and strong CYP2D6 inhibitors. If concomitant use is necessary, monitor for signs and symptoms of possible primaquine treatment failure. Risk D: Consider Therapy Modification
Procyclidine: PARoxetine may increase serum concentration of Procyclidine. Risk C: Monitor
Propafenone: CYP2D6 Inhibitors (Strong) may increase serum concentration of Propafenone. Risk C: Monitor
Propranolol: CYP2D6 Inhibitors (Strong) may increase serum concentration of Propranolol. Risk C: Monitor
Psilocybin: Antidepressants may decrease therapeutic effects of Psilocybin. Risk C: Monitor
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
Ramosetron: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Rasagiline: Selective Serotonin Reuptake Inhibitor may increase serotonergic effects of Rasagiline. This could result in serotonin syndrome. Risk X: Avoid
RisperiDONE: CYP2D6 Inhibitors (Strong) may increase serum concentration of RisperiDONE. Management: Careful monitoring for risperidone toxicities and possible dose adjustment are recommended when combined with strong CYP2D6 inhibitors. See full interaction monograph for details. Risk D: Consider Therapy Modification
Safinamide: May increase serotonergic effects of Selective Serotonin Reuptake Inhibitor. This could result in serotonin syndrome. Risk X: Avoid
Selective Serotonin Reuptake Inhibitor: May increase serotonergic effects of Selective Serotonin Reuptake Inhibitor. This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitor may increase antiplatelet effects of Selective Serotonin Reuptake Inhibitor. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, mental status changes) when these agents are combined. In addition, monitor for signs and symptoms of bleeding. Risk C: Monitor
Selegiline: Selective Serotonin Reuptake Inhibitor may increase serotonergic effects of Selegiline. This could result in serotonin syndrome. Risk X: Avoid
Selumetinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Serotonergic Agents (High Risk, Miscellaneous): May increase serotonergic effects of Selective Serotonin Reuptake Inhibitor. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Serotonergic Non-Opioid CNS Depressants: Selective Serotonin Reuptake Inhibitor may increase serotonergic effects of Serotonergic Non-Opioid CNS Depressants. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Serotonergic Opioids (High Risk): May increase serotonergic effects of Selective Serotonin Reuptake Inhibitor. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) if these agents are combined. Risk C: Monitor
Serotonin 5-HT1D Receptor Agonists (Triptans): May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Serotonin/Norepinephrine Reuptake Inhibitor: Selective Serotonin Reuptake Inhibitor may increase serotonergic effects of Serotonin/Norepinephrine Reuptake Inhibitor. This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitor may increase antiplatelet effects of Serotonin/Norepinephrine Reuptake Inhibitor. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, mental status changes) when these agents are combined. In addition, monitor for signs and symptoms of bleeding. Risk C: Monitor
Sertindole: CYP2D6 Inhibitors (Strong) may increase serum concentration of Sertindole. Management: Consider alternatives to this combination when possible. If combined, consider using lower doses of sertindole and monitor the ECG closely for evidence of QTc interval prolongation. Risk D: Consider Therapy Modification
Sofpironium: CYP2D6 Inhibitors (Strong) may increase serum concentration of Sofpironium. Risk X: Avoid
St John's Wort: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. St John's Wort may decrease serum concentration of Serotonergic Agents (High Risk). Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Syrian Rue: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Tamoxifen: CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of Tamoxifen. Specifically, strong CYP2D6 inhibitors may decrease the metabolic formation of highly potent active metabolites. Management: Avoid concurrent use of strong CYP2D6 inhibitors with tamoxifen when possible, as the combination may be associated with a reduced clinical effectiveness of tamoxifen. Risk D: Consider Therapy Modification
Tamsulosin: CYP2D6 Inhibitors (Strong) may increase serum concentration of Tamsulosin. Risk C: Monitor
Tetrabenazine: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Tetrabenazine. Specifically, concentrations of the active alpha- and beta-dihydrotetrabenazine metabolites may be increased. Management: Limit the tetrabenazine dose to 50 mg per day (25 mg per single dose) in patients taking strong CYP2D6 inhibitors. Risk D: Consider Therapy Modification
Thiazide and Thiazide-Like Diuretics: Selective Serotonin Reuptake Inhibitor may increase hyponatremic effects of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor
Thioridazine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Thioridazine. Risk X: Avoid
Thrombolytic Agents: Agents with Antiplatelet Effects may increase adverse/toxic effects of Thrombolytic Agents. Specifically, the risk of bleeding may be increased. Risk C: Monitor
Thyroid Products: Selective Serotonin Reuptake Inhibitor may decrease therapeutic effects of Thyroid Products. Thyroid product dose requirements may be increased. Risk C: Monitor
Tilidine: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Timolol (Ophthalmic): CYP2D6 Inhibitors (Strong) may increase serum concentration of Timolol (Ophthalmic). Risk C: Monitor
Timolol (Systemic): CYP2D6 Inhibitors (Strong) may increase serum concentration of Timolol (Systemic). Risk C: Monitor
Tipranavir: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Tolterodine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Tolterodine. Risk C: Monitor
TraMADol: Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may increase adverse/toxic effects of TraMADol. Specifically, the risk for serotonin syndrome/serotonin toxicity and seizures may be increased. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may decrease therapeutic effects of TraMADol. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes), seizures, and decreased tramadol efficacy when these agents are combined. Risk C: Monitor
Tricyclic Antidepressants: PARoxetine may increase serotonergic effects of Tricyclic Antidepressants. PARoxetine may increase serum concentration of Tricyclic Antidepressants. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased TCA concentrations/effects if these agents are combined. Risk D: Consider Therapy Modification
Valbenazine: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Valbenazine. Management: Reduce valbenazine dose to 40 mg once daily when combined with a strong CYP2D6 inhibitor. Monitor for increased valbenazine effects/toxicities. Risk D: Consider Therapy Modification
Vasopressin: Drugs Suspected of Causing SIADH may increase therapeutic effects of Vasopressin. Specifically, the pressor and antidiuretic effects of vasopressin may be increased. Risk C: Monitor
Venlafaxine: May increase antiplatelet effects of Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors). Venlafaxine may increase serotonergic effects of Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors). This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may decrease active metabolite exposure of Venlafaxine. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may increase serum concentration of Venlafaxine. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, mental status changes) when these agents are combined. In addition, monitor for signs and symptoms of bleeding. Risk C: Monitor
Vitamin E (Systemic): May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Vitamin K Antagonists: Antidepressants with Antiplatelet Effects may increase anticoagulant effects of Vitamin K Antagonists. Risk C: Monitor
Volanesorsen: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Vortioxetine: Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may increase serotonergic effects of Vortioxetine. This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may increase antiplatelet effects of Vortioxetine. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may increase serum concentration of Vortioxetine. Management: Consider alternatives to this drug combination. If combined, reduce the vortioxetine dose by half and monitor for signs and symptoms of bleeding and serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, autonomic instability). Risk D: Consider Therapy Modification
Xanomeline: CYP2D6 Inhibitors (Strong) may increase serum concentration of Xanomeline. Risk C: Monitor
Zanubrutinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Ziprasidone: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor
Zuclopenthixol: CYP2D6 Inhibitors (Strong) may increase serum concentration of Zuclopenthixol. Risk C: Monitor
Peak concentration is increased, but bioavailability is not significantly altered by food. Management: Administer without regard to meals.
Evaluate pregnancy status prior to initiating treatment in patients who could become pregnant. Treatment should not be withheld, but pharmacologic management may vary based on reproductive status, severity of illness, and history of antidepressant response (ACOG 2023; WFSBP [Dodd 2018]). When treating depression, anxiety, obsessive-compulsive disorder (OCD), or post-traumatic stress disorder (PTSD), selective serotonin reuptake inhibitors (SSRIs) are preferred for use prior to conception in patients who are treatment naive or who do not have a history of effective treatment. Patients effectively treated may continue their current medication when planning a pregnancy unless contraindications exist (BAP [McAllister-Williams 2017]). Management of mental health conditions in patients who could become pregnant should be based on a shared decision-making process that considers the possibility of pregnancy during treatment (ACOG 2023; BAP [McAllister-Williams 2017]; CANMAT [MacQueen 2016]).
Paroxetine is also approved for the treatment of premenstrual dysphoric disorder. Symptom-onset dosing, which is initiated on the day of symptom onset and continued until after the start of menses, may be beneficial in patients attempting to conceive (Lanza di Scalea 2019).
Menstrual changes, including amenorrhea and dysmenorrhea, have been reported with paroxetine. SSRI use may cause hyperprolactinemia and, rarely, changes in thyroid function, both of which can be associated with menstrual irregularities. Depression is also associated with menstrual changes (Padda 2021).
Some studies suggest SSRIs may impair semen parameters, including the motility of spermatozoa; use of other treatments may be preferred in patients planning a pregnancy (ISSM [Althof 2014]; Sylvester 2019). SSRIs are associated with an increased risk of sexual dysfunction (Tarchi 2023). Paroxetine may delay ejaculation and is used off label for the treatment of premature ejaculation (ISSM [Althof 2014]; Sathianathen 2021).
Paroxetine crosses the placenta (Yue 2023).
As a class, selective serotonin reuptake inhibitors (SSRIs) have been evaluated extensively in pregnant patients. Studies focusing on newborn outcomes following first trimester SSRI exposure often have inconsistent results. A less than 2-fold risk of cardiovascular malformations may be associated with paroxetine; however, data evaluating the risk of specific defects following paroxetine use vary when considering differences in study design and confounders (ACOG 2023; Anderson 2020; BAP [McAllister-Williams 2017]; Biffi 2020; Fitton 2020; Gao 2018; Lebin 2022).
Adverse effects in the newborn following SSRI exposure in the third trimester include neonatal adaptation syndrome and persistent pulmonary hypertension of the newborn (PPHN). Neonatal adaptation syndrome can occur shortly after birth and typically resolves within 2 weeks. Mechanisms of neonatal adaptation syndrome are not well understood but may be due to either SSRI toxicity or withdrawal. Reducing the dose or discontinuing the SSRI prior to delivery to reduce the risk of neonatal adaptation syndrome is not recommended (ACOG 2023). Symptoms can include apnea, constant crying, cyanosis, feeding difficulty, hyperreflexia, hypo- or hypertonia, hypoglycemia, irritability, jitteriness, respiratory distress, seizures, temperature instability, tremor, and vomiting. Prolonged hospitalization, respiratory support, or tube feedings may be required.
Persistent pulmonary hypertension of the newborn is a rare complication of SSRI use during pregnancy with symptoms of respiratory distress within the first hours of life and an increased risk of neonatal mortality (ACOG 2023). Monitoring of infants exposed to SSRIs late in pregnancy is recommended (Masarwa 2019; Ng 2019). Data related to the long-term effects of in utero SSRI exposure on infant neurodevelopment and behavior are limited (CANMAT [MacQueen 2016]; Lebin 2022).
SSRIs may increase the risk of bleeding. Exposure late in pregnancy is associated with less than a 2-fold increase in postpartum hemorrhage. The clinical significance of this is uncertain (BAP [McAllister-Williams 2017]; Lebin 2022).
Due to pregnancy-induced physiologic changes, some pharmacokinetic parameters of paroxetine may be altered. Paroxetine plasma concentrations may decrease as pregnancy progresses; however, the maternal CYP2D6 genotype also influence the change in paroxetine plasma concentrations during pregnancy (Hostetter 2000; Ververs 2009; Westin 2017; Yue 2023). A case report describes symptoms of antidepressant discontinuation syndrome (night sweats, nightmares) in a patient during the first trimester of pregnancy, requiring a continued increase of her paroxetine dose as pregnancy progressed for resolution. The patient was found to be an extensive metabolizer of CYP2D6 (Javelot 2020). Close clinical monitoring as pregnancy progresses and therapeutic drug monitoring to detect patterns of changing plasma concentrations is recommended to assist dose adjustment when needed; CYP2D6 genotyping may also be considered (Schoretsanitis 2020).
Untreated and undertreated mental health conditions are associated with adverse pregnancy outcomes. Untreated or undertreated depression is associated with preterm birth, low birth weight (LBW), preeclampsia, postpartum depression, and impaired infant attachment (associated with long-term developmental effects). Anxiety disorders during pregnancy are associated with LBW, preterm birth, and adverse behavioral outcomes in the offspring. Discontinuing effective medications during pregnancy increases the risk of relapse. Management should be made as part of a shared decision-making process (ACOG 2023).
Patients effectively treated for depression, anxiety, obsessive-compulsive disorder (OCD) or post-traumatic stress disorder (PTSD) in the past may use that medication during pregnancy unless contraindications exist (ACOG 2023; BAP [McAllister-Williams 2017]; CANMAT [MacQueen 2016]). Treatment should not be withheld or discontinued based only on pregnancy status (ACOG 2023). SSRIs are preferred for use in pregnant patients who are treatment naive or who do not have a history of effective treatment in the past. An SSRI other than paroxetine may be preferred for pregnant patients with no prior medication history (ACOG 2023).
When medications are used, the lowest effective dose of a single agent is recommended. Optimize dosing prior to changing a medication or adding additional agents whenever possible. Monthly monitoring for symptom improvement with a validated screening tool during pregnancy is recommended. Manage side effects as needed (ACOG 2023).
Menopausal vasomotor symptoms do not occur during pregnancy; therefore, the use of paroxetine for the treatment of menopausal vasomotor symptoms is contraindicated in pregnant patients.
Data collection to monitor pregnancy and infant outcomes following exposure to antidepressant medications is ongoing. Pregnant patients 45 years of age and younger with a history of psychiatric illness are encouraged to enroll in the National Pregnancy Registry for Antidepressants (1-866-961-2388 or https://womensmentalhealth.org/research/pregnancyregistry/antidepressants/).
Paroxetine is present in breast milk.
Multiple reports summarize data related to the presence of paroxetine in breast milk:
• A review article used pooled data from 119 mother/infant pairs to calculate the estimated daily infant dose of paroxetine via breast milk to be 0.03 mg/day providing a relative infant dose (RID) of 0.5% to 3%. The maternal dose and actual breast milk concentrations for the calculation were not provided (Berle 2011).
• A second review article included information from 228 cases; maternal daily doses of paroxetine were 5 to 60 mg/day. The highest breast milk concentration of paroxetine presented was 776 ng/mL observed in 1 of 4 women following a maternal dose of 12.5 to 60 mg/day obtained after 0 to 18 weeks of treatment. The highest RID presented was 2.9% from a study that included 7 patients taking paroxetine 20 to 40 mg/day for 6 to 30 week (Orsolini 2015).
• A study published since these reviews included 5 lactating women taking paroxetine 7 to 25 mg/day; the paroxetine breast milk concentrations and RID fell within the ranges presented in the earlier reviews. The highest calculated RID was 3.2% following a maternal dose of paroxetine 25 mg/day, providing a milk concentration of 32.9 ng/mL (Pogliani 2019).
• Breast milk and maternal plasma concentrations are linearly correlated (Misri 2000; Weissman 2004).
• Paroxetine was measurable in the serum of some breastfed infants (Orsolini 2015; Weissman 2004).
• In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000). However, some sources note breastfeeding should only be considered if the RID is <5% for psychotropic agents (Anderson 2021).
Adverse events following exposure to selective serotonin reuptake inhibitors (SSRIs) via breast milk have been reported in some infants. Constant crying, hypotonia, insomnia, irritability, lethargy, poor weight gain, and restlessness have been observed in breastfed infants exposed to SSRIs, including paroxetine (Lanza di Scalea 2009; Merlob 2004; Orsolini 2015; Uguz 2016; Weissman 2004); severe constipation was also observed in a case report following paroxetine exposure (Uguz 2018). Infants exposed to an SSRI via breast milk should be monitored for irritability and changes in sleep, feeding patterns, and behavior as well as growth and development (ABM [Sriraman 2015]; BAP [McAllister-Williams 2017]; Weissman 2004).
Maternal use of an SSRI during pregnancy may delay lactogenesis (Marshall 2010); however, the underlying maternal illness and various other factors may also influence this outcome. Patients who wish to breastfeed during treatment with an SSRI may need additional assistance to initiate and maintain breastfeeding (Anderson 2021).
Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends a decision be made to discontinue breastfeeding or to discontinue paroxetine, considering the importance of treatment to the mother. Patients effectively treated for depression, anxiety, obsessive-compulsive disorder (OCD), or post-traumatic stress disorder (PTSD) during pregnancy may continue their medication postpartum unless contraindications to breastfeeding exist. The presence and concentration of the drug in breast milk, efficacy of maternal treatment, and infant age should be considered when initiating a medication for the first-time postpartum patient. When first initiating an antidepressant in a patient who is treatment naive and breastfeeding, paroxetine may be used; however, other agents should be considered if the patient requires long-term therapy and wishes to have another pregnancy (ABM [Sriraman 2015]; CANMAT [MacQueen 2016]). Breastfeeding may be continued in patients treated with an SSRI during pregnancy (ABM [Sriraman 2015]; ACOG 2023). Treatment should not be withheld or discontinued based only on breastfeeding status (ACOG 2023).
Liver and renal function tests (baseline; as clinically indicated); serum sodium in at-risk populations (as clinically indicated); CBC (as clinically indicated); closely monitor patients for depression, clinical worsening, suicidality, psychosis, or unusual changes in behavior (eg, anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, mania), particularly during the initial 1 to 2 months of therapy or during periods of dosage adjustments (increases or decreases).
Paroxetine is a selective serotonin reuptake inhibitor, chemically unrelated to tricyclic, tetracyclic, or other antidepressants; presumably, the inhibition of serotonin reuptake from brain synapse stimulated serotonin activity in the brain
Onset of action:
Anxiety disorders (generalized anxiety, obsessive-compulsive, panic, and posttraumatic stress disorder): Initial effects may be observed within 2 weeks of treatment, with continued improvements through 4 to 6 weeks (Issari 2016; Varigonda 2016; WFSBP [Bandelow 2023a]); some experts suggest up to 12 weeks of treatment may be necessary for response, particularly in patients with obsessive-compulsive disorder and posttraumatic stress disorder (BAP [Baldwin 2014]; Katzman 2014; WFSBP [Bandelow 2023a]; WFSBP [Bandelow 2023b]).
Body dysmorphic disorder: Initial effects may be observed within 2 weeks; some experts suggest up to 12 to 16 weeks of treatment may be necessary for response in some patients (Phillips 2008).
Depression: Initial effects may be observed within 1 to 2 weeks of treatment, with continued improvements through 4 to 6 weeks (Papakostas 2006; Posternak 2005; Szegedi 2009; Taylor 2006b).
Premenstrual dysphoric disorder: Initial effects may be observed within the first few days of treatment, with response at the first menstrual cycle of treatment (ISPMD [Nevatte 2013]).
Absorption: Completely absorbed following oral administration
Distribution: Vd: 8.7 L/kg (3 to 28 L/kg)
Protein binding: 93% to 95%
Metabolism: Extensively hepatic via CYP2D6 enzymes; primary metabolites are formed via oxidation and methylation of parent drug, with subsequent glucuronide/sulfate conjugation; nonlinear pharmacokinetics (via 2D6 saturation) may be seen with higher doses and longer duration of therapy. Metabolites exhibit ~2% potency of parent compound. Cmin concentrations are 70% to 80% greater in the elderly compared to nonelderly patients; clearance is also decreased.
Bioavailability: Immediate release tablet and oral suspension have equal bioavailability
Half-life elimination: Paxil: 21 hours; Paxil CR: 15 to 20 hours; Pexeva: 33.2 hours
Time to peak:
Capsules: Median: 6 hours (range: 3 to 8 hours)
Tablets, oral suspension: Immediate release: Mean: 5.2 to 8.1 hours
Tablets: Controlled release: 6 to 10 hours
Excretion: Urine (64%, 2% as unchanged drug); feces (36% primarily via bile, <1% as unchanged drug)
Altered kidney function: AUC increased approximately 3.5 times with CrCl <30 mL/minute. AUC increased 2-fold with CrCl 30 to 60 mL/minute (Doyle 1989).
Hepatic function impairment: 2-fold increase in plasma concentrations and AUC after 14 days of daily administration in patients with alcohol-related cirrhosis (Dalhoff 1991).
Older adult: Minimum concentrations were 70% to 80% greater than in younger patients. Reduce initial dosage; no dosage adjustment is necessary with Brisdelle.
