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Citalopram: Drug information

Citalopram: Drug information
(For additional information see "Citalopram: Patient drug information" and see "Citalopram: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Suicidal thoughts and behaviors:

Antidepressants increased the risk of suicidal thinking 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. Citalopram is not approved for use in pediatric patients.

Brand Names: US
  • CeleXA
Brand Names: Canada
  • ACCEL-Citalopram [DSC];
  • ACT Citalopram [DSC];
  • AG-Citalopram;
  • APO-Citalopram;
  • Auro-Citalopram;
  • BIO-Citalopram;
  • CCP-Citalopram;
  • CeleXA;
  • Citalopram-10;
  • Citalopram-20;
  • Citalopram-40;
  • CTP 30;
  • DOM-Citalopram;
  • Mar-Citalopram;
  • MINT-Citalopram;
  • NAT-Citalopram;
  • NATCO-Citalopram;
  • NRA-Citalopram;
  • PMS-Citalopram;
  • Priva-Citalopram [DSC];
  • RAN-Citalo [DSC];
  • RIVA-Citalopram;
  • SANDOZ Citalopram [DSC];
  • SEPTA-Citalopram;
  • TEVA-Citalopram;
  • VAN-Citalopram [DSC]
Pharmacologic Category
  • Antidepressant, Selective Serotonin Reuptake Inhibitor
Dosing: Adult

Note: Maximum daily dose: Due to the risk of QT prolongation, the maximum recommended daily dose for all indications is 40 mg. A lower maximum daily dose of 20 mg is recommended in patients >60 years of age, those with significant hepatic impairment, and patients who are concurrently receiving medications that significantly increase citalopram levels (eg, cimetidine, omeprazole) or known poor metabolizers of CYP2C19 substrates. Initial dose and titration: In patients sensitive to side effects, some experts suggest a lower starting dose of 10 mg daily and gradual titration in increments of no more than 10 mg, particularly in patients with anxiety who are generally more sensitive to overstimulation effects (eg, anxiety, insomnia) with antidepressants (Ref).

Aggressive or agitated behavior associated with dementia

Aggressive or agitated behavior associated with dementia (off-label use): Oral: Initial: 10 mg once daily; increase to 20 mg once daily after ≥3 days. In adults ≤60 years, may further increase dose based on response and tolerability up to 30 mg/day (Ref); for adults >60 years, do not exceed the maximum dose of 20 mg/day.

Binge eating disorder

Binge eating disorder (off-label use): Oral: Initial: 20 mg once daily. In adults ≤60 years of age, may gradually increase dose based on response and tolerability at intervals ≥1 week to 40 mg once daily. Although doses up to 60 mg/day have been studied, due to safety considerations the recommended maximum dose is 40 mg/day for adults ≤60 years of age and 20 mg/day for adults >60 years (Ref).

Generalized anxiety disorder

Generalized anxiety disorder (off-label use): Oral: Initial: 10 mg once daily; may gradually increase dose based on response and tolerability in 10 mg increments at intervals ≥1 week to a maximum dose of 40 mg/day for adults ≤60 years and 20 mg/day for adults >60 years of age (Ref).

Major depressive disorder

Major depressive disorder (unipolar): Oral: Initial: 20 mg once daily. In adults ≤60 years of age, may gradually increase dose based on response and tolerability at intervals ≥1 week to a maximum dose of 40 mg/day; for adults >60 years of age, do not exceed the maximum dose of 20 mg/day. Daily doses that exceeded these limits have been studied but are not recommended due to safety considerations.

Obsessive-compulsive disorder

Obsessive-compulsive disorder (off-label use): Oral: Initial: 20 mg once daily. In adults ≤60 years of age, may gradually increase dose based on response and tolerability in 10 to 20 mg increments at intervals ≥1 week to a maximum dose of 40 mg/day; for adults >60 years of age, do not exceed the maximum dose of 20 mg/day. Daily doses that exceeded these limits have been studied but are not recommended due to safety considerations (Ref). Note: An adequate trial for assessment of effect in obsessive-compulsive disorder is considered to be ≥6 weeks at maximum tolerated dose (Ref).

Panic disorder

Panic disorder (off-label use): Oral: Initial: 10 mg once daily for 3 to 7 days, then 20 mg once daily. In adults ≤60 years, may gradually increase dose based on response and tolerability in 10 to 20 mg increments at intervals ≥1 week to a maximum of 40 mg/day; for adults >60 years of age, do not exceed the maximum dose of 20 mg/day. Daily doses that exceeded these limits have been studied but are not recommended due to safety considerations (Ref).

Posttraumatic stress disorder

Posttraumatic stress disorder (off-label use): Oral: Initial: 20 mg once daily. In adults ≤60 years of age, may gradually increase dose based on response and tolerability in 10 to 20 mg increments at intervals ≥1 week to a maximum dose of 40 mg once daily; for adults >60 years of age, do not exceed the maximum dose of 20 mg/day. Daily doses that exceeded these limits have been studied but are not recommended due to safety considerations (Ref).

Premature ejaculation

Premature ejaculation (off-label use): Oral: Initial: 20 mg once daily. In adults ≤60 years of age, may gradually increase dose based on response and tolerability at intervals of ≥1 week (some experts suggest 3- to 4-week titration intervals (Ref)) up to a maximum of 40 mg/day (Ref); for adults >60 years of age, do not exceed the maximum dose of 20 mg/day.

Premenstrual dysphoric disorder

Premenstrual dysphoric disorder (PMDD) (off-label use):

Continuous daily dosing regimen: Oral: Initial: 10 mg once daily; over the first month increase to usual effective dose of 20 mg once daily; in subsequent menstrual cycles, further dose increases (eg, in 10 mg increments per menstrual cycle) up to 40 mg/day may be necessary in some patients for optimal response (Ref).

Intermittent regimens:

Luteal phase dosing regimen: 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 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).

Symptom-onset dosing regimen: 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 increase to usual effective dose of 20 mg once daily; 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

Social anxiety disorder (off-label use): Oral: Initial: 10 to 20 mg once daily. In adults ≤60 years of age, after ~6 weeks may gradually increase dose based on response and tolerability in 10 to 20 mg increments at intervals ≥1 week up to maximum of 40 mg/day; for adults >60 years of age, do not exceed the maximum dose of 20 mg/day. Daily doses that exceeded these limits have been studied but are not recommended due to safety considerations (Ref).

Vasomotor symptoms associated with menopause

Vasomotor symptoms associated with menopause (alternative agent) (off-label use): Oral: Initial: 10 mg once daily; may increase dose to 20 mg once daily after 1 week. In adults ≤60 years of age, doses as high as 40 mg/day have been studied; however, doses >20 mg/day have demonstrated little additional benefit and greater adverse effects (Ref). For adults >60 years of age, do not exceed the maximum dose of 20 mg/day.

Dosage adjustments: For concomitant therapy with moderate to strong CYP2C19 inhibitors or other drugs that significantly increase citalopram levels (eg, cimetidine, omeprazole, voriconazole) and in persons who are known to be poor metabolizers of CYP2C19: Maximum dose: 20 mg/day.

Discontinuation of therapy:When discontinuing antidepressant treatment that has lasted for >3 weeks, gradually taper the dose (eg, over 2 to 4 weeks) to minimize withdrawal symptoms and detect reemerging symptoms (Ref). Reasons for a slower taper (eg, over 4 weeks) include use of a drug with a half-life <24 hours (eg, paroxetine, venlafaxine), 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 citalopram.

Allow 14 days to elapse between discontinuing citalopram 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.

Dosing: Kidney Impairment: Adult

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.

Note: Limited pharmacokinetic data are available in patients with severe kidney impairment and on hemodialysis (Ref).

Altered kidney function:

CrCl ≥20 mL/minute: No dosage adjustment necessary.

CrCl <20 mL/minute: Initial: 10 mg once daily; gradually titrate based on tolerability and response with close monitoring for adverse effects (eg, QT prolongation) (Ref).

Hemodialysis, intermittent (thrice weekly): Neither citalopram nor its active metabolite, desmethylcitalopram, are significantly dialyzed (1% (Ref)):

Note: An increase in sudden cardiac death in hemodialysis patients prescribed selective serotonin reuptake inhibitors (SSRIs) with higher QT-prolonging potential (citalopram, escitalopram) compared to SSRIs with lower QT-prolonging potential was observed in a retrospective cohort study (Ref). Therefore, use of an SSRI with a lower QT-prolonging potential may be preferred.

Initial: 10 mg once daily; gradually titrate based on tolerability and response with close monitoring for adverse effects (eg, QT prolongation) (Ref).

Peritoneal dialysis: Unlikely to be significantly dialyzed (highly protein bound, large Vd) (Ref):

Note: An increase in sudden cardiac death in hemodialysis patients prescribed SSRIs with higher QT-prolonging potential (citalopram, escitalopram) compared to SSRIs with lower QT-prolonging potential was observed in a retrospective cohort study (Ref). A similar risk has not been observed in patients on peritoneal dialysis (has not been studied), but use of an SSRI with a lower QT-prolonging potential may be preferred.

Initial: 10 mg once daily; gradually titrate based on tolerability and response with close monitoring for adverse effects (eg, QT prolongation) (Ref).

Dosing: Hepatic Impairment: Adult

Maximum recommended dose: 20 mg/day due to decreased clearance and the risk of QT prolongation.

Dosing: Pediatric

(For additional information see "Citalopram: Pediatric drug information")

Note: Citalopram therapy should be initiated at a low dose with a slow titration to reduce the potential for behavioral activation/agitation that may occur with therapy initiation particularly in younger children (Ref). Doses >40 mg/day are not recommended due to risk of QTc prolongation.

Anxiety disorders

Anxiety disorders (generalized, social, or separation anxiety, or panic 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 (eg, QT prolongation) (Ref).

Children ≥7 years to <12 years: Oral: Initial range: 2.5 to 10 mg once daily; titrate to target daily dose range: 10 to 20 mg/day. In trials, an initial dose of 10 mg/day titrated slowly every 1 to 2 weeks was reported; however, subsequent expert recommendations suggest in younger patients that lower initial doses (<10 mg) and slow titration be used to prevent dose-related behavioral activation/agitation that may occur early in treatment; some data based on trials treating OCD (a type of anxiety disorder) (Ref).

Children ≥12 years and Adolescents: Initial: 10 mg once daily; titrate at 1- to 2-week intervals up to a target daily dose of 20 to 40 mg/day (Ref).

Depression

Depression: Limited data available; efficacy results variable:

Note: In the management of depression in children and adolescents, if pharmacotherapy deemed necessary with/without psychotherapeutic interventions, an SSRI should be used first-line; citalopram is an alternative SSRI option for patients in which fluoxetine is not an option (Ref).

Children ≥7 years and Adolescents: Oral: Initial: 10 mg once daily; increase dose slowly by 10 mg/day every 1 to 2 weeks as clinically needed; reported effective dosage range: 20 to 40 mg/day (Ref).

Note: One randomized, placebo-controlled trial has shown citalopram to be effective for the treatment of depression in pediatric patients (Wagner 2004); other controlled pediatric trials have not shown benefit (Ref).

Obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD): Limited data available:

Note: In the management of OCD in children and adolescents, if pharmacotherapy deemed necessary with/without psychotherapeutic interventions, an SSRI should be used first-line; a preferred agent has not been identified although fluoxetine and sertraline have FDA approval for OCD in pediatric patients (Ref).

Children ≥7 years: Oral: Initial: 2.5 to 10 mg once daily (Ref); in trials, doses were increased by 5 mg/day every 2 weeks as clinically needed; dosage range: 10 to 40 mg/day; children required higher mg/kg doses than adolescent patients (Ref).

Adolescents: Oral: 10 to 20 mg once daily (Ref); in trials, doses were increased by 10 mg/day every 2 weeks as clinically needed; dosage range: 10 to 40 mg/day (Ref).

Discontinuation of therapy: Consider planning antidepressant discontinuation for lower-stress times, recognizing non-illness-related factors could cause stress or anxiety and be misattributed to antidepressant discontinuation (Ref). Upon discontinuation of antidepressant 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 limited. APA and NICE guidelines suggest tapering therapy over at least several weeks with consideration to the half-life of the antidepressant; antidepressants with a shorter half-life may need to be tapered more conservatively. After long-term (years) antidepressant treatment, WFSBP guidelines recommend tapering over 4 to 6 months, with close monitoring during and for 6 months after discontinuation. If intolerable discontinuation symptoms occur following a dose reduction, consider resuming the previously prescribed dose and/or decrease dose at a more gradual rate (Ref).

Switching antidepressants: Evidence for ideal antidepressant 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 monoamine 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.

Dosing: Kidney Impairment: Pediatric

Specific recommendations in pediatric patients are not available; based on experience in adult patients, in mild to moderate impairment, no adjustment needed, and in severe impairment, use with caution (has not been studied).

Dosing: Hepatic Impairment: Pediatric

Specific recommendations in pediatric patients are not available; based on experience in adult patients, consider reduced daily doses due to increased serum concentrations and the risk of QT prolongation.

Dosing: Older Adult

Note: For patients >60 years of age, the maximum recommended dose is 20 mg/day due to the risk of QT prolongation.

Generalized anxiety disorder (off-label use): Oral: Initial: 10 mg once daily; may increase dose based on response and tolerability in 10 mg increments at intervals ≥1 week up to 20 mg/day. Doses up to 40 mg/day have been studied; however, according to the manufacturer, dosing should not exceed 20 mg/day (Ref).

Major depressive disorder (unipolar): Adults >60 years: Oral: Initial: 10 to 20 mg once daily (Ref); maximum dose: 20 mg/day due to increased exposure and the risk of QT prolongation.

Discontinuation of therapy: Refer to adult dosing.

Switching antidepressants: Refer to adult dosing.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral, as hydrobromide:

Generic: 30 mg

Solution, Oral:

Generic: 10 mg/5 mL (10 mL, 240 mL, 473 mL)

Tablet, Oral:

CeleXA: 10 mg

CeleXA: 20 mg, 40 mg [scored]

Generic: 10 mg, 20 mg, 40 mg

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

CeleXA: 20 mg, 40 mg

CTP 30: 30 mg

Generic: 10 mg, 20 mg, 40 mg

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Citalopram capsules: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215428s000lbl.pdf#page=23

Citalopram tablets: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/020822s052lbl.pdf#page=26, must be dispensed with this medication.

Administration: Adult

Oral: May be administered without regard to food.

Administration: Pediatric

Oral: May be administered without regard to meals.

Use: Labeled Indications

Major depressive disorder (unipolar): Treatment of unipolar major depressive disorder in adults.

Use: Off-Label: Adult

Aggressive or agitated behavior associated with dementia; Binge eating disorder; Generalized anxiety disorder; Obsessive-compulsive disorder; Panic disorder; Posttraumatic stress disorder; Premature ejaculation; Premenstrual dysphoric disorder; Social anxiety disorder; Vasomotor symptoms associated with menopause

Medication Safety Issues
Sound-alike/look-alike issues:

CeleXA may be confused with CeleBREX, Cerebyx, Ranexa, ZyPREXA

Older Adult: High-Risk Medication:

Beers Criteria: Selective Serotonin Reuptake Inhibitors (SSRIs) are identified in the Beers Criteria as potentially inappropriate medications to be used with caution in patients 65 years and older because of the potential to cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatremia; monitor sodium concentration closely when initiating or adjusting the dose in older adults (Beers Criteria [AGS 2019]).

Adverse Reactions (Significant): Considerations
Activation of mania or hypomania

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).

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).

Risk factors:

• Family history of bipolar disorder (Ref)

• Depressive episode with psychotic symptoms (Ref)

• Younger age at onset of depression (Ref)

• Antidepressant resistance (Ref)

• Female sex (Ref)

Bleeding risk

Selective serotonin reuptake inhibitors (SSRIs), including citalopram, may increase the risk of bleeding, particularly if used concomitantly with antiplatelets and/or anticoagulants. Multiple observational studies have found an association with SSRI use and a variety of bleeding complications, ranging from bruising, hematomas, petechiae, purpuric disease, and epistaxis to cerebrovascular accident, upper gastrointestinal hemorrhage, intracranial hemorrhage, postpartum hemorrhage (exposure during late gestation), vaginal hemorrhage, and perioperative bleeding, although conflicting evidence also exists (Ref).

Mechanism: Possibly via inhibition of serotonin-mediated platelet activation (inhibition of the serotonin reuptake transporter) and subsequent platelet dysfunction. Citalopram is considered to display moderate 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 upper GI bleeding, 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 upper GI bleeding (Ref)

Fragility fractures

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).

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). An increased tendency to falls 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).

Risk factors:

• Long-term use may be a risk factor (Ref)

Hyponatremia

Selective serotonin reuptake inhibitors (SSRIs) are associated with syndrome of inappropriate antidiuretic hormone secretion (SIADH) and/or hyponatremia, including severe cases, predominantly in the elderly (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 (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)

Ocular effects

Selective serotonin reuptake inhibitors (SSRIs) are associated with acute angle-closure glaucoma (AACG) in case reports and a case-control 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 that 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)

QT prolongation

Dose-dependent prolonged QT interval on ECG and torsades de pointes (TdP) have been reported, particularly in patients with coexisting risk factors for QT effects (Ref). Citalopram is associated with a greater effect on QTc prolongation (mean QTc increase 7.8 ms [10 to 20 mg citalopram] and 10.3 ms [20 to 40 mg citalopram]) compared to escitalopram; however, the clinical significance of citalopram’s effect on QT prolongation in patients without additional risk factors receiving usual therapeutic doses has been questioned (Ref).

Mechanism: Dose-related; citalopram is believed to cause QTc prolongation via direct blockade of the rapid potassium delayed rectifier current (IKr), encoded by the human ether-à-go-go-related gene (hERG) (Ref).

Risk factors:

In general, risk factors for drug-induced QT prolongation/TdP:

• Females (Ref)

• Age >65 (Ref)

• Structural heart disease (eg, history of myocardial infarction or heart failure with a reduced ejection fraction) (Ref)

• History of drug-induced TdP (Ref)

• Genetic defects of cardiac ion channels (Ref)

• Congenital long QT syndrome (Ref)

• Baseline QTc interval prolongation (eg, >500 msec) or lengthening of the QTc by ≥60 msec (Ref)

• Electrolyte disturbances (eg, hypokalemia, hypocalcemia, or hypomagnesemia) (Ref)

• Bradycardia (Ref)

• Hepatic impairment (Ref)

• Kidney impairment (Ref)

• Coadministration of multiple medications (≥2) that prolong the QT interval or increase drug interactions that increase serum drug concentrations of QT-prolonging medications (Ref)

• Substance use (Ref)

Serotonin syndrome

Serotonin syndrome has been reported and typically occurs with coadministration of multiple serotonergic drugs but can occur following a single serotonergic agent at therapeutic doses (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 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 [MAOIs]). Of note, concomitant use of some serotonergic agents, such as MAOIs, are contraindicated.

Sexual dysfunction

Selective serotonin reuptake inhibitors (SSRIs) are commonly associated with sexual disorder in both men and women. The following adverse reactions have been associated with SSRI use: Orgasm abnormal, anorgasmia, erectile dysfunction, and decreased libido (Ref). Priapism and decreased genital sensation have also been reported with SSRIs (Ref).

Mechanism: 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)

Suicidal thinking and behavior

Antidepressants are associated with an increased risk of suicidal ideation and suicidal tendencies in pediatric and young adult patients (18 to 24 years of age) in short-term studies. In adults >24 years of age, 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 longer-term use (ie, >4 months).

Risk factors:

• Children and adolescents (Ref)

• Depression (risk of suicide is associated with major depression and may persist until remission occurs)

Withdrawal syndrome

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, mania) have been reported, primarily following abrupt discontinuation. 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 gradual dosage reduction) of an antidepressant treatment that has lasted >3 weeks, particularly a drug with a half-life <24 hours (eg, paroxetine, venlafaxine) (Ref)

• Prior history of antidepressant withdrawal symptoms (Ref)

• High dose (Ref)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Dermatologic: Diaphoresis (11%; dose related)

Gastrointestinal: Nausea (21%), xerostomia (20%)

Nervous system: Drowsiness (18%; dose related; literature suggests incidence occurs less frequently in children and adolescents compared to adults [Safer 2006]), insomnia (15%; dose related)

1% to 10%:

Cardiovascular: Bradycardia (1%), hypotension (≥1%), orthostatic hypotension (≥1%), prolonged QT interval on ECG (2%) (Hasnain 2014) (table 1), tachycardia (≥1%)

Citalopram: Adverse Reaction: Prolonged QT Interval on ECG

Drug (Citalopram)

Placebo

Number of Patients (Citalopram)

Number of Patients (Placebo)

2%

1%

802

241

Dermatologic: Pruritus (≥1%), skin rash (≥1%)

Endocrine & metabolic: Amenorrhea (≥1%), decreased libido (1% to 4%) (table 2), weight gain (≥1%), weight loss (≥1%)

Citalopram: Adverse Reaction: Decreased Libido

Drug (Citalopram)

Placebo

Population

Number of Patients (Citalopram)

Number of Patients (Placebo)

1%

N/A

Females

638

N/A

4%

<1%

Males

425

194

2%

<1%

Males and females

1,063

446

Gastrointestinal: Abdominal pain (3%), anorexia (4%), diarrhea (8%), dysgeusia (≥1%), dyspepsia (5%), flatulence (≥1%), increased appetite (≥1%), sialorrhea (≥1%), vomiting (4%; literature suggests incidence is higher in adolescents compared to adults, and is two- to threefold higher in children compared to adults [Safer 2006])

Genitourinary: Dysmenorrhea (3%), ejaculatory disorder (6%) (table 3), impotence (3%; dose related) (table 4)

Citalopram: Adverse Reaction: Ejaculatory Disorder

Drug (Citalopram)

Placebo

Number of Patients (Citalopram)

Number of Patients (Placebo)

6%

1%

1,063

446

Citalopram: Adverse Reaction: Impotence

Drug (Citalopram)

Placebo

Number of Patients (Citalopram)

Number of Patients (Placebo)

3%

<1%

425

194

Nervous system: Agitation (3%), amnesia (≥1%), anxiety (4%), apathy (≥1%), confusion (≥1%), depression (≥1%), fatigue (5%; dose related), lack of concentration (≥1%), migraine (≥1%), paresthesia (≥1%), yawning (2%; dose related)

Neuromuscular & skeletal: Arthralgia (2%), myalgia (2%), tremor (8%)

Ophthalmic: Accommodation disturbance (≥1%)

Renal: Polyuria (≥1%)

Respiratory: Cough (≥1%), rhinitis (5%), sinusitis (3%), upper respiratory tract infection (5%)

Miscellaneous: Fever (2%)

<1%:

Cardiovascular: Acute myocardial infarction, angina pectoris, atrial fibrillation, bundle branch block, cardiac failure, cerebrovascular accident, extrasystoles, facial edema, flushing, hypertension, ischemic heart disease, peripheral edema, phlebitis, pulmonary embolism, syncope, transient ischemic attacks

Dermatologic: Acne vulgaris, alopecia, cellulitis, dermatitis, eczema, hypertrichosis, hypohidrosis, psoriasis, skin discoloration, skin photosensitivity, urticaria, xeroderma

Endocrine & metabolic: Altered serum glucose, dehydration, galactorrhea not associated with childbirth, goiter, gynecomastia, hot flash, hypoglycemia, hypokalemia, hyponatremia (literature suggests incidence of hyponatremia among SSRIs ranges from <1% to as high as 32% [Jacob 2006]) (Flores 2004), hypothyroidism, increased libido, increased thirst, obesity

Gastrointestinal: Bruxism, cholecystitis, cholelithiasis, colitis, diverticulitis of the gastrointestinal tract, duodenal ulcer, dysphagia, eructation, esophagitis, gastric ulcer, gastritis, gastroenteritis, gastroesophageal reflux disease, gingival hemorrhage, gingivitis, glossitis, hemorrhoids, hiccups, melanosis, pruritus ani, stomatitis

Genitourinary: Breast hypertrophy, dysuria, hematuria, mastalgia, oliguria, urinary incontinence, urinary retention, vaginal hemorrhage (Durmaz 2015)

Hematologic & oncologic: Anemia, disorder of hemostatic components of blood, hypochromic anemia, leukocytosis, leukopenia, lymphadenopathy, lymphocytopenia, lymphocytosis, purpuric disease

Hepatic: Hepatitis, hyperbilirubinemia, increased liver enzymes, increased serum alkaline phosphatase, jaundice

Nervous system: Abnormal gait, aggressive behavior, ataxia, catatonia, delusion, depersonalization, drug dependence, dystonia (Moosavi 2014), emotional lability, euphoria, extrapyramidal reaction, hallucination, hyperesthesia, hypertonia, hypoesthesia, involuntary muscle movements, myasthenia, neuralgia, nightmares, panic attack, paranoid ideation, psychosis, rigors, seizure, serotonin syndrome (Tseng 2005), stupor, vertigo

Neuromuscular & skeletal: Arthritis, bursitis, hyperkinetic muscle activity, hypokinesia, lower limb cramp, osteoporosis, skeletal pain

Ophthalmic: Abnormal lacrimation, blepharoptosis, cataract, conjunctivitis, diplopia, dry eye syndrome, eye pain, keratitis, mydriasis, photophobia

Otic: Tinnitus

Renal: Nephrolithiasis, pyelonephritis, renal pain

Respiratory: Asthma, bronchitis, bronchospasm, dyspnea, epistaxis, flu-like symptoms, laryngitis, pneumonia, pneumonitis, seasonal allergic rhinitis

Frequency not defined: Nervous system: Suicidal ideation (Coughlin 2016), suicidal tendencies (Zisook 2009)

Postmarketing:

Cardiovascular: Chest pain, Raynaud's disease (Khouri 2016; Peiró 2007), thrombosis, torsades de pointes (de Gregorio 2011), ventricular arrhythmia

Dermatologic: Ecchymoses, erythema multiforme, toxic epidermal necrolysis

Endocrine & metabolic: Increased serum prolactin, orgasm abnormal (unknown; Clayton 2015; Montejo 2001), SIADH (Odeh 2011)

Gastrointestinal: Gastrointestinal hemorrhage (Bixby 2019, Opatrny 2008), pancreatitis

Genitourinary: Erectile dysfunction (Montejo 2001), priapism (rare: <1%) (including clitoral priapism) (Berk 1997; Reisman 2017), sexual difficulty (decreased genital sensation) (rare: <1%) (Csoka 2008), sexual disorder (persistent post-SSRI) (rare: <1%) (Csoka 2008), sexual disorder (common: ≥10%) (Higgins 2010, Montejo 2001)

Hematologic & oncologic: Hemolytic anemia, hypoprothrombinemia, thrombocytopenia (Andersohn 2009)

Hepatic: Hepatic necrosis

Hypersensitivity: Anaphylaxis, angioedema, hypersensitivity reaction

Nervous system: Akathisia, anorgasmia (Clayton 2015; Montejo 2001), choreoathetosis, delirium, hyperactive behavior (agitation, hyperactivation, hyperkinesis, restlessness occurring in children at a two- to threefold higher incidence compared to adolescents [Safer 2006]), mania (rare: <1%) (Pravin 2004), myoclonus, neuroleptic malignant syndrome (Stevens 2008), withdrawal syndrome (Fava 2015)

Neuromuscular & skeletal: Dyskinesia (Gaanderse 2016), rhabdomyolysis

Ophthalmic: Acute angle-closure glaucoma (rare: <1%) (Croos 2005; Massaoutis 2007), nystagmus disorder

Renal: Acute renal failure

Contraindications

Hypersensitivity to citalopram or any component of the formulation; use of MAO inhibitors intended to treat psychiatric disorders (concurrently or within 14 days of discontinuing either citalopram or the MAO inhibitor); initiation of citalopram in a patient receiving linezolid or intravenous methylene blue; concomitant use with pimozide

Canadian labeling: Additional contraindications (not in US labeling): Known QT interval prolongation or congenital long QT syndrome

Warnings/Precautions

Concerns related to adverse effects:

• CNS depression: Has a low potential to impair cognitive or motor performance; caution operating hazardous machinery or driving.

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with hepatic impairment; clearance is decreased and half-life and plasma concentrations are increased. Dosage adjustment may be required.

• Renal impairment: Use with caution in patients with severe renal impairment; dosage adjustments may be necessary with severe dysfunction.

• Seizure disorders: Use with caution in patients with a previous seizure disorder or condition predisposing to seizures such as brain damage or alcoholism.

Special populations:

• CYP2C19 poor metabolizers: Citalopram exposure and maximum concentrations are increased in CYP2C19 poor metabolizers; a maximum daily dose of 20 mg/day is recommended in these patients.

• Older adult: Pharmacokinetics are altered in patients >60 years of age.

• Pediatric: Citalopram is not FDA-approved for use in children; however, if used, monitor weight and growth regularly during therapy due to the potential for decreased appetite and weight loss with SSRI use.

Metabolism/Transport Effects

Substrate of CYP2C19 (major), CYP2D6 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2D6 (weak)

Drug Interactions

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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Abrocitinib: Agents with Antiplatelet Properties may enhance the antiplatelet effect of Abrocitinib. Management: Do not use antiplatelet drugs with abrocitinib during the first 3 months of abrocitinib therapy. The abrocitinib prescribing information lists this combination as contraindicated. This does not apply to low dose aspirin (81 mg/day or less). Risk X: Avoid combination

Acalabrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. Risk C: Monitor therapy

Agents with Blood Glucose Lowering Effects: Selective Serotonin Reuptake Inhibitors may enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Alcohol (Ethyl): May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. 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 enhance the serotonergic effect 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 therapy

Alosetron: May enhance the serotonergic effect 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 therapy

Amisulpride (Oral): May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk C: Monitor therapy

Amphetamines: May enhance the serotonergic effect 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). Initiate amphetamines at lower doses, monitor frequently, and adjust doses as needed. Risk C: Monitor therapy

Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect 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 therapy

Antipsychotic Agents: Serotonergic Agents (High Risk) may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor therapy

Apixaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Apixaban. Specifically, the risk for bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely. Risk C: Monitor therapy

Aspirin: Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Aspirin. Risk C: Monitor therapy

Bemiparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin with antiplatelet agents. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Brexanolone: Selective Serotonin Reuptake Inhibitors may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy

Bromopride: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Risk X: Avoid combination

BuPROPion: May enhance the adverse/toxic effect of Citalopram. BuPROPion may increase the serum concentration of Citalopram. Management: Initiate citalopram at the lower end of the normal dose range in patients receiving bupropion and consider limiting the maximum citalopram adult dose to 20 mg/day during concomitant bupropion treatment. Monitor for citalopram toxicities. Risk D: Consider therapy modification

BusPIRone: May enhance the serotonergic effect 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 therapy

Caplacizumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Caplacizumab. Specifically, the risk of bleeding may be increased. Management: Avoid coadministration of caplacizumab with antiplatelets if possible. If coadministration is required, monitor closely for signs and symptoms of bleeding. Interrupt use of caplacizumab if clinically significant bleeding occurs. Risk D: Consider therapy modification

Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. Risk C: Monitor therapy

Cimetidine: May increase the serum concentration of Citalopram. Management: Limit citalopram dose to a maximum of 20 mg/day if used with cimetidine. Patients using this combination should be monitored closely for evidence of citalopram toxicity (eg, serotonin syndrome, QT prolongation). Risk D: Consider therapy modification

CloZAPine: May enhance the QTc-prolonging effect of Citalopram. CloZAPine may enhance the serotonergic effect of Citalopram. This could result in serotonin syndrome. Management: Monitor for QTc interval prolongation, ventricular arrhythmias, serotonin syndrome, and neuroleptic malignant syndrome when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Collagenase (Systemic): Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and or bleeding may be increased. Risk C: Monitor therapy

Cyclobenzaprine: May enhance the serotonergic effect 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 therapy

CYP2C19 Inhibitors (Moderate): May increase the serum concentration of Citalopram. Management: Limit citalopram dose to a maximum of 20 mg/day if used with a moderate CYP2C19 inhibitor. Patients using this combination should be monitored closely for evidence of citalopram toxicity (eg, serotonin syndrome, QT prolongation). Risk D: Consider therapy modification

CYP3A4 Inducers (Strong): May decrease the serum concentration of Citalopram. Risk C: Monitor therapy

Cyproheptadine: May diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Risk C: Monitor therapy

Dabigatran Etexilate: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Dabigatran Etexilate. Agents with Antiplatelet Properties may increase the serum concentration of Dabigatran Etexilate. This mechanism applies specifically to clopidogrel. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Risk C: Monitor therapy

Dabrafenib: May enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Dapoxetine: May enhance the serotonergic effect 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 combination

Deoxycholic Acid: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Risk C: Monitor therapy

Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy

Dexmethylphenidate-Methylphenidate: May enhance the serotonergic effect 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 therapy

Dextromethorphan: May enhance the serotonergic effect 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 therapy

Domperidone: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Domperidone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

DULoxetine: Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of DULoxetine. Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of DULoxetine. This could result in serotonin syndrome. 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 therapy

Edoxaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Risk C: Monitor therapy

Eletriptan: May enhance the serotonergic effect 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 therapy

Enoxaparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue antiplatelet agents prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Ergot Derivatives: May enhance the serotonergic effect 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 therapy

Escitalopram: Citalopram may enhance the antiplatelet effect of Escitalopram. Escitalopram may enhance the QTc-prolonging effect of Citalopram. Escitalopram may enhance the serotonergic effect of Citalopram. This could result in serotonin syndrome. Risk X: Avoid combination

Esomeprazole: May increase the serum concentration of Citalopram. Management: Limit citalopram dose to a maximum of 20 mg/day if used with esomeprazole. Patients using this combination should be monitored closely for evidence of citalopram toxicity (eg, serotonin syndrome, QT prolongation, etc.). Risk D: Consider therapy modification

Fenfluramine: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor therapy

Fexinidazole: May enhance the QTc-prolonging effect of Citalopram. Fexinidazole may increase the serum concentration of Citalopram. Management: Limit citalopram dose to a maximum of 20 mg/day if used with fexinidazole, which is a moderate CYP2C19 inhibitor. Monitor for citalopram toxicity (eg, serotonin syndrome), QTc prolongation, and arrhythmias (including torsades de pointes). Risk D: Consider therapy modification

Fluconazole: May enhance the QTc-prolonging effect of Citalopram. Fluconazole may increase the serum concentration of Citalopram. Management: Limit citalopram dose to a maximum of 20 mg/day if used with fluconazole, which is a strong CYP2C19 inhibitor. Patients using this combination should be monitored closely for citalopram toxicities, including serotonin syndrome and QT prolongation. Risk D: Consider therapy modification

Fluorouracil Products: May enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

FLUoxetine: Citalopram may enhance the antiplatelet effect of FLUoxetine. Citalopram may enhance the serotonergic effect of FLUoxetine. This could result in serotonin syndrome. FLUoxetine may increase the serum concentration of Citalopram. Management: Limit citalopram dose to a maximum of 20 mg/day. Monitor for signs and symptoms of bleeding, QTc interval prolongation, or serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor) if combined. Risk D: Consider therapy modification

FluvoxaMINE: Citalopram may enhance the antiplatelet effect of FluvoxaMINE. Citalopram may enhance the serotonergic effect of FluvoxaMINE. This could result in serotonin syndrome. FluvoxaMINE may increase the serum concentration of Citalopram. Management: Limit citalopram dose to a maximum of 20 mg/day. Monitor for signs and symptoms of bleeding, QTc prolongation, or serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor) if combined. Risk D: Consider therapy modification

Gilteritinib: Citalopram may enhance the QTc-prolonging effect of Gilteritinib. Gilteritinib may diminish the therapeutic effect of Citalopram. Management: Avoid use of this combination if possible. If use is necessary, monitor for reduced response to citalopram and for QTc prolongation and arrhythmias. Patients with other risk factors may be at greater risk for these serious toxicities. Risk D: Consider therapy modification

Haloperidol: QT-prolonging Antidepressants (Moderate Risk) may enhance the QTc-prolonging effect of Haloperidol. Haloperidol may enhance the serotonergic effect of QT-prolonging Antidepressants (Moderate Risk). This could result in serotonin syndrome. Management: Monitor for QTc interval prolongation, ventricular arrhythmias, and serotonin syndrome/serotonin toxicity (SS/ST) or NMS when these agents are combined. Patients with additional risk factors for QTc prolongation or SS/ST may be at even higher risk. Risk C: Monitor therapy

Heparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or agents with antiplatelet properties if coadministration is required. Risk D: Consider therapy modification

Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Risk C: Monitor therapy

Hydroxychloroquine: Citalopram may enhance the hypoglycemic effect of Hydroxychloroquine. Hydroxychloroquine may enhance the QTc-prolonging effect of Citalopram. Risk C: Monitor therapy

Ibritumomab Tiuxetan: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Risk C: Monitor therapy

Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Icosapent Ethyl: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Inotersen: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Ioflupane I 123: Selective Serotonin Reuptake Inhibitors may diminish the diagnostic effect of Ioflupane I 123. Risk C: Monitor therapy

Lasmiditan: May enhance the serotonergic effect 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 therapy

Levoketoconazole: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Levoketoconazole. Risk X: Avoid combination

Levomethadone: May enhance the serotonergic effect 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 therapy

Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Linezolid: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Risk X: Avoid combination

Lipid Emulsion (Fish Oil Based): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Lofexidine: May enhance the QTc-prolonging effect of Citalopram. Citalopram may enhance the QTc-prolonging effect of Lofexidine. 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 therapy

Lorcaserin (Withdrawn From US Market): May enhance the serotonergic effect 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 therapy

Metaxalone: May enhance the serotonergic effect 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 therapy

Methylene Blue: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. Risk X: Avoid combination

Metoclopramide: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Consider monitoring 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 therapy

MetyroSINE: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Risk C: Monitor therapy

Mivacurium: Selective Serotonin Reuptake Inhibitors may increase the serum concentration of Mivacurium. Risk C: Monitor therapy

Monoamine Oxidase Inhibitors (Antidepressant): Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Risk X: Avoid combination

Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Nefazodone: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. 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 therapy

Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective). Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents (Nonselective): Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. 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 enhance the antiplatelet effect of Selective Serotonin Reuptake Inhibitors. Risk C: Monitor therapy

Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Risk C: Monitor therapy

Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Omeprazole: May increase the serum concentration of Citalopram. Management: Limit citalopram dose to a maximum of 20 mg/day if used with omeprazole. Monitor for evidence of citalopram toxicity (eg, serotonin syndrome, QT prolongation) in patients receiving this combination. Risk D: Consider therapy modification

Ondansetron: May enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Ondansetron may enhance the serotonergic effect of QT-prolonging Antidepressants (Moderate Risk). This could result in serotonin syndrome. Management: Monitor for QTc interval prolongation, ventricular arrhythmias, and serotonin syndrome when these agents are combined. Patients with additional risk factors for QTc prolongation or serotonin syndrome may be at even higher risk. Risk C: Monitor therapy

Opioid Agonists: May enhance the serotonergic effect 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 therapy

Opioid Agonists (metabolized by CYP3A4 and CYP2D6): May enhance the serotonergic effect 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 therapy

Opioid Agonists (metabolized by CYP3A4): May enhance the serotonergic effect 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 therapy

Oxitriptan: Serotonergic Agents (High Risk) may enhance the serotonergic effect 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 therapy

Ozanimod: May enhance the adverse/toxic effect of Serotonergic Agents (High Risk). Risk C: Monitor therapy

Pentamidine (Systemic): May enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate 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 therapy

Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Risk C: Monitor therapy

Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Perhexiline: Citalopram may increase the serum concentration of Perhexiline. Risk C: Monitor therapy

Pimozide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination

Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

QT-prolonging Agents (Highest Risk): May enhance the QTc-prolonging effect of Citalopram. Risk X: Avoid combination

QT-prolonging Antidepressants (Moderate Risk): Citalopram may enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Citalopram may enhance the serotonergic effect of QT-prolonging Antidepressants (Moderate Risk). This could result in serotonin syndrome. Citalopram may increase the serum concentration of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation, ventricular arrhythmias, and serotonin syndrome when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Antipsychotics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). QT-prolonging Antipsychotics (Moderate Risk) may enhance the serotonergic effect of QT-prolonging Antidepressants (Moderate Risk). This could result in serotonin syndrome. Management: Monitor for QTc interval prolongation, ventricular arrhythmias, and serotonin syndrome/serotonin toxicity (SS/ST) or NMS when these agents are combined. Patients with additional risk factors for QTc prolongation or SS/ST may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Class IC Antiarrhythmics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate 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 therapy

QT-Prolonging Inhalational Anesthetics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Kinase Inhibitors (Moderate Risk): QT-prolonging Antidepressants (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate 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 therapy

QT-prolonging Miscellaneous Agents (Moderate Risk): QT-prolonging Antidepressants (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate 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 therapy

QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): Citalopram may enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Citalopram. Risk C: Monitor therapy

QT-prolonging Quinolone Antibiotics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate 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 therapy

QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): Citalopram may enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Citalopram. 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 therapy

Ramosetron: May enhance the serotonergic effect 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 therapy

Rasagiline: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Rasagiline. This could result in serotonin syndrome. Risk X: Avoid combination

Rivaroxaban: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Rivaroxaban. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Risk C: Monitor therapy

Safinamide: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Use the lowest effective dose of SSRIs in patients treated with safinamide and monitor for signs and symptoms of serotonin syndrome/serotonin toxicity. Risk D: Consider therapy modification

Salicylates: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Risk C: Monitor therapy

Selective Serotonin Reuptake Inhibitors: Citalopram may enhance the antiplatelet effect of Selective Serotonin Reuptake Inhibitors. Citalopram may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. 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 therapy

Selegiline: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Selegiline. This could result in serotonin syndrome. Risk X: Avoid combination

Selumetinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Serotonergic Agents (High Risk, Miscellaneous): May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. 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 therapy

Serotonergic Non-Opioid CNS Depressants: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect 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 therapy

Serotonergic Opioids (High Risk): May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. 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 therapy

Serotonin 5-HT1D Receptor Agonists (Triptans): May enhance the serotonergic effect 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 therapy

Serotonin/Norepinephrine Reuptake Inhibitors: Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Serotonin/Norepinephrine Reuptake Inhibitors. Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. This could result in serotonin syndrome. 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 therapy

Sertindole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination

St John's Wort: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. St John's Wort may decrease the 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 therapy

Syrian Rue: May enhance the serotonergic effect 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 therapy

Thiazide and Thiazide-Like Diuretics: Selective Serotonin Reuptake Inhibitors may enhance the hyponatremic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy

Thyroid Products: Selective Serotonin Reuptake Inhibitors may diminish the therapeutic effect of Thyroid Products. Thyroid product dose requirements may be increased. Risk C: Monitor therapy

Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

TraMADol: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk for serotonin syndrome/serotonin toxicity and seizures may be increased. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and seizures when these agents are combined. Risk C: Monitor therapy

Tricyclic Antidepressants: May enhance the serotonergic effect of Citalopram. Tricyclic Antidepressants may increase the serum concentration of Citalopram. Citalopram may increase the 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 and citalopram concentrations/effects. Risk C: Monitor therapy

Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. Risk X: Avoid combination

Vasopressin: Drugs Suspected of Causing SIADH may enhance the therapeutic effect of Vasopressin. Specifically, the pressor and antidiuretic effects of vasopressin may be increased. Risk C: Monitor therapy

Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Selective Serotonin Reuptake Inhibitors may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Voriconazole: Citalopram may enhance the QTc-prolonging effect of Voriconazole. Voriconazole may increase the serum concentration of Citalopram. Management: Limit citalopram dose to a maximum of 20 mg/day if used with voriconazole, which is a moderate CYP2C19 inhibitor. Monitor for citalopram toxicity (eg, serotonin syndrome), QTc prolongation, and arrhythmias (including torsades de pointes). Risk D: Consider therapy modification

Zanubrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Reproductive Considerations

Citalopram is approved for the treatment of unipolar major depressive disorder. If treatment for major depressive disorder is initiated for the first time in patients planning to become pregnant, citalopram is one of the preferred selective serotonin reuptake inhibitors (SSRIs) (Larsen 2015).

Citalopram is also used off label for the treatment of premenstrual dysphoric disorder. For patients attempting to conceive, symptom-onset dosing may be beneficial to minimize potential fetal exposure (Ismaili 2016; Lanza di Scalea 2019).

SSRIs may be associated with male and female treatment-emergent sexual dysfunction (Coskuner 2018; WFSBP [Bauer 2013]). Decreased libido and anorgasmia have been reported in females; abnormal ejaculation, decreased libido, and impotence have been reported in males with citalopram use. This may also be a manifestation of the psychiatric disorder. The actual risk associated with citalopram is not known. SSRI-related sexual dysfunction may resolve with dose reduction or discontinuation of the SSRI; in some cases, sexual dysfunction may persist once therapy is discontinued (Coskuner 2018; Jing 2016; Waldinger 2015).

Citalopram is used off label for the treatment of premature ejaculation. Although data are limited, some studies have shown SSRIs may impair the motility of spermatozoa; therefore, use of other treatments may be preferred in patients planning to father a child (Althof 2014; Siroosbakht 2019; Sylvester 2019).

Pregnancy Considerations

Citalopram and its metabolites cross the human placenta (Paulzen 2017).

As a class, selective serotonin reuptake inhibitors (SSRIs) have been evaluated extensively in pregnant patients. Studies focusing on newborn outcomes following first trimester exposure often have inconsistent results due to differences in study design and confounders such as maternal disease and social factors (Anderson 2020; Biffi 2020; Fitton 2020; Reefhuis 2015; Womersley 2017). Adverse effects in the newborn following SSRI exposure late in the third trimester 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. Symptoms may be due to the toxicity of the SSRIs or a discontinuation syndrome and may be consistent with serotonin syndrome associated with SSRI treatment. Persistent pulmonary hypertension of the newborn has been reported with SSRI exposure; although the absolute risk is small, monitoring of infants exposed to SSRIs late in pregnancy is recommended (Masarwa 2019; Ng 2019). The long-term effects of in utero SSRI exposure on infant neurodevelopment and behavior are not known (CANMAT [MacQueen 2016]).

Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of citalopram may be altered. In addition, changes in maternal CYP2D6 and CYP2C19 activity also influence citalopram and metabolite concentrations. 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 (Paulzen 2017; Schoretsanitis 2020).

If treatment for major depressive disorder is initiated for the first time during pregnancy, citalopram is one of the preferred SSRIs (CANMAT [MacQueen 2016]; Larsen 2015; WFSBP [Bauer 2013]). Untreated or inadequately treated psychiatric illness may lead to poor adherence with prenatal care and adverse pregnancy outcomes. Therapy with antidepressants during pregnancy should be individualized; treatment with antidepressant medication is recommended for pregnant patients with severe major depressive disorder (ACOG 2008; CANMAT [MacQueen 2016]). Patients treated for major depression and who are euthymic prior to pregnancy are more likely to experience a relapse when medication is discontinued (68%) as compared to pregnant patients who continue taking antidepressant medications (26%) (Cohen 2006).

Data collection to monitor pregnancy and infant outcomes following exposure to antidepressant medications is ongoing. Patients exposed to antidepressants during pregnancy are encouraged to enroll in the National Pregnancy Registry for Antidepressants. Pregnant patients 18 to 45 years of age or their health care providers may contact the registry to enroll; enrollment should be done as early in pregnancy as possible (1-866-961-2388 or https://womensmentalhealth.org/research/pregnancyregistry/antidepressants/)

Breastfeeding Considerations

Citalopram and its active metabolites are present in breast milk.

The relative infant dose (RID) of citalopram has been calculated in review articles to be 0.2% to 10% of the weight adjusted maternal dose (Berle 2011; Orsolini 2015); RIDs up to 18% have also been located (Pogliani 2019). In general, breastfeeding is considered acceptable when the RID is <10% (Anderson 2016; Ito 2000); however, some sources note breastfeeding should only be considered if the RID is <5% for psychotropic agents (Larsen 2015). When the RID is >25% breastfeeding should generally be avoided (Anderson 2016; Ito 2000).

In one review, the RID of citalopram was calculated using pooled data from 80 mother/infant pairs, providing an estimated daily infant dose via breast milk of 0.14 mg/day. The maternal dose and actual breast milk concentrations for the calculation were not provided (Berle 2011). A second review included information from 112 cases; maternal daily doses of citalopram were 10 to 60 mg/day. The highest breast milk concentrations of citalopram presented were 340 to 1190 ng/mL following maternal doses of 10 to 60 mg/day from a study of 3 women (postpartum age not stated), providing an RID of 3.2% to 5.1%; the active metabolite was also present in breast milk. Citalopram and the metabolite were detected in the serum of some infants (Orsolini 2015). A study published since these reviews included 2 lactating women taking citalopram 5 and 10 mg/day; although the citalopram breast milk concentrations fell within the ranges reported in the earlier reviews (95.4 ng/mL and 62.6 ng/mL, respectively; collected ~3 days postpartum), authors of this study calculated the RIDs to be 13.2% and 18.4% (Pogliani 2019). Active metabolites of citalopram can also be detected in breast milk. Peak milk concentrations of citalopram and desmethylcitalopram occur 4 and 6 hours, respectively, after the maternal dose in women on chronic therapy (Rampono 2000). However, avoiding breastfeeding during the expected peak concentrations will generally not decrease infant exposure significantly for antidepressants with long half-lives (Berle 2011). Although the absolute infant plasma concentrations are generally negligible, in some cases the infant plasma concentration of citalopram was up to 10% of the maternal concentration (Berle 2011). Based on available data, infants exposed to citalopram via breast milk are more likely to have elevated citalopram plasma concentrations in comparison to those exposed to other selective serotonin reuptake inhibitors (SSRIs) (Weissman 2004).

Excessive somnolence, decreased feeding, and weight loss have been noted in infants exposed to citalopram from breast milk. Alternately, a case report describes tolerance to citalopram in an infant exposed via breast milk following adverse events with exposure to other SSRIs. Treatment was first initiated in a mother diagnosed with major depressive disorder 3 weeks postpartum, first with sertraline, then paroxetine. Adverse events occurred in the exclusively breastfed infant with both medications, resolving when each were discontinued. Treatment with citalopram was then initiated, resulting in effective therapy for the mother and no adverse events in the infant (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]; Sachs 2013; Weissman 2004; WFSBP [Bauer 2013]).

Maternal use of an SSRI during pregnancy may cause delayed lactogenesis (Marshall 2010); however, the underlying maternal illness may also influence this outcome (Grzeskowiak 2018). Untreated severe or chronic depression in the postpartum period also has negative effects on the mother and the infant (Slomian 2019).

Psychotherapy or other nonmedication therapies are recommended for the initial treatment of mild depression in breastfeeding patients; antidepressant medication is recommended when psychotherapy is not an option or symptoms are moderate to severe. If a specific SSRI was used effectively during pregnancy, it can be continued while breastfeeding if no contraindications exist (ABM [Sriraman 2015]. According to the manufacturer, the decision to continue or discontinue breastfeeding during citalopram therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. When first initiating an antidepressant in a breastfeeding patient, agents other than citalopram are preferred (ABM [Sriraman 2015]; Larsen 2015).

Dietary Considerations

May be taken without regard to food.

Monitoring Parameters

ECG (patients at increased risk for QT-prolonging effects due to certain conditions); electrolytes (potassium and magnesium concentrations [prior to initiation and periodically during therapy in patients at increased risk for electrolyte abnormalities]); 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); signs/symptoms of serotonin syndrome such as mental status changes (eg, agitation, hallucinations, delirium, coma), autonomic instability (eg, tachycardia, labile BP, diaphoresis), neuromuscular changes (eg, tremor, rigidity, myoclonus), GI symptoms (eg, nausea, vomiting, diarrhea), and/or seizures.

Mechanism of Action

A racemic bicyclic phthalane derivative, citalopram selectively inhibits serotonin reuptake in the presynaptic neurons and has minimal effects on norepinephrine or dopamine. Uptake inhibition of serotonin is primarily due to the S-enantiomer of citalopram. Displays little to no affinity for serotonin, dopamine, adrenergic, histamine, GABA, or muscarinic receptor subtypes.

Pharmacokinetics

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 2012]); 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 2012]).

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 2006).

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]).

Duration: 1 to 2 days.

Distribution: Vd: 12 L/kg.

Protein binding, plasma: ~80%.

Metabolism: Extensively hepatic, via CYP3A4 and 2C19 (major pathways), and 2D6 (minor pathway); metabolized to demethylcitalopram (DCT), didemethylcitalopram (DDCT), citalopram-N-oxide, and a deaminated propionic acid derivative, which are at least eight times less potent than citalopram.

Bioavailability: 80%; tablets and oral solution are bioequivalent.

Half-life elimination: 24 to 48 hours (average: 35 hours); doubled with hepatic impairment and increased by 30% (following multiple doses) to 50% (following single dose) in elderly patients (≥60 years).

Time to peak, serum: 1 to 6 hours, average within 4 hours.

Excretion: Urine (Citalopram 10% and DCT 5%).

Pharmacokinetics: Additional Considerations

Altered kidney function: Oral clearance decreased 17% in mild to moderate renal impairment. Limited information is available in patients with severe impairment (Joffe 1998; Spigset 2000).

Hepatic function impairment: Oral clearance decreased 37%, half-life doubled, and plasma concentrations increased in reduced hepatic function.

Older adult: Multiple dose: AUC increased 23% and half-life increased 30%. Single dose: AUC increased 30% and half-life increased 50%.

Sex: AUC in women was 1.5 to 2 times that in men in 3 studies; no difference was observed in 5 other studies.

CYP2C19 poor metabolizers: Steady state Cmax and AUC increased by 68% and 107%, respectively.

Pricing: US

Capsules (Citalopram Hydrobromide Oral)

30 mg (per each): $5.88

Solution (Citalopram Hydrobromide Oral)

10 mg/5 mL (per mL): $0.49 - $0.98

Tablets (CeleXA Oral)

10 mg (per each): $10.89

20 mg (per each): $11.35

40 mg (per each): $11.85

Tablets (Citalopram Hydrobromide Oral)

10 mg (per each): $2.43 - $2.58

20 mg (per each): $2.53 - $2.69

40 mg (per each): $2.64 - $2.78

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.

Brand Names: International
  • Ansiodex (PY);
  • Arpolax (BD, HK);
  • Celapram (AU, BR, NZ);
  • Celica (AU);
  • Ceropam (EG);
  • Cimal (CL);
  • Ciprager (IE);
  • Cipram (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, GR, HK, ID, IQ, IR, JO, KE, KR, KW, LB, LR, LY, MA, ML, MR, MU, MW, MY, NE, NG, OM, PK, QA, SA, SC, SD, SG, SL, SN, SY, TH, TN, TR, TW, TZ, UG, YE, ZM, ZW);
  • Cipramax (EG);
  • Cipramil (AU, BE, BR, CL, CN, DE, DK, EE, GB, IE, IL, LU, NL, NO, NZ, PE, RU, SE, UA, VN, ZA);
  • Ciprotan (IE);
  • Ciram (SG);
  • Citaalogen (JO);
  • Citadep (LK);
  • Cital (PL);
  • Citalo (EG);
  • Citalogen (AE, BH, KW, QA, SA);
  • Citalon (HR);
  • Citalvir (ES);
  • Citapram (BD);
  • Citaxin (PL);
  • Citazone (CO);
  • Citia (AR, BR);
  • Citopam (IN, LK);
  • Citox (MX);
  • Citrol (IE);
  • Denyl (BR);
  • Depaway (EG);
  • Duo Fo (CN);
  • Feliz (IN, LK, PH);
  • Humorap (PY);
  • Kitapram (TW);
  • Lecital (BH, EG, LB, QA, SA);
  • Lenepal (AR);
  • Linisan (RO);
  • Lopram (AE, BH, KW, QA);
  • Lowdep (VN);
  • Oropram (MT);
  • Pram (UA);
  • Prepram (MX);
  • Prisdal (ES);
  • Psiconor (UY);
  • Recital (IL);
  • Sepram (FI);
  • Seropram (AT, BG, CH, CZ, ES, FR, GR, HU, IT, MX, VE);
  • Sitalo (TW);
  • Starcitin (HR);
  • Talam (AU, HK);
  • Talosin (MT);
  • Tazen (PH);
  • Ultidep (TW);
  • Xylorane (MX);
  • Zentius (AR, CL, EC);
  • Zinetron (MX);
  • Zitolex (PT)


For country code abbreviations (show table)
  1. 2019 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2019 Updated AGS Beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2019;67(4):674-694. doi:10.1111/jgs.15767 [PubMed 30693946]
  2. Aigner M, Treasure J, Kaye W, Kasper S; WFSBP Task Force on Eating Disorders. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of eating disorders. World J Biol Psychiatry. 2011;12(6):400-443. doi:10.3109/15622975.2011.602720 [PubMed 21961502]
  3. Ailawadhi S, Sung KW, Carlson LA, Baer MR. Serotonin syndrome caused by interaction between citalopram and fentanyl. J Clin Pharm Ther. 2007;32(2):199-202. doi:10.1111/j.1365-2710.2007.00813.x [PubMed 17381671]
  4. Althof SE, McMahon CG, Waldinger M, et al. An update of the International Society of Sexual Medicine’s guidelines for the diagnosis and treatment of premature ejaculation (PE). Sexual Med. 2014;2(2):60-90. doi:10.1002/sm2.28 [PubMed 25356302]
  5. Alvarez PA, Pahissa J. QT alterations in psychopharmacology: proven candidates and suspects. Curr Drug Saf. 2010;5(1):97-104. doi:10.2174/157488610789869265 [PubMed 20210726]
  6. American Academy of Child and Adolescent Psychiatry (AACAP). Practice parameter for the assessment and treatment of children and adolescents with obsessive-compulsive disorder. J Am Acad Child Adolesc Psychiatry. 2012;51(1):98-113. doi:10.1016/j.jaac.2011.09.019 [PubMed 22176943]
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