Citalopram (Monograph)

Brand name: CeleXA
Drug class: Selective Serotonin-reuptake Inhibitors
- Serotonin-reuptake Inhibitors
- SSRIs
VA class: CN609
Chemical name: 1-[3-(Dimethylamino)-propyl]-1-(p-fluorophenyl)-5-phthalancarbonitrile
Molecular formula: C₂₀H₂₁FN₂O
CAS number: 59729-33-8

Medically reviewed by Drugs.com on Sep 15, 2023. Written by ASHP.

Warning

Antidepressants increased risk of suicidal thinking and behavior (suicidality) compared with placebo in children, adolescents, and young adults (18–24 years of age) with major depressive disorder and other psychiatric disorders; balance this risk with clinical need.³⁷⁰ ³⁷¹ ³⁹⁹ Citalopram is not approved for use in pediatric patients.³⁹⁹ (See Pediatric Use under Cautions.)
In pooled data analyses, risk of suicidality was not increased in adults >24 years of age and was reduced in adults ≥65 years of age with antidepressants compared with placebo.³⁷⁰ ³⁷¹ ³⁹⁹
Depression and certain other psychiatric disorders are themselves associated with an increased risk of suicide.³⁷⁰ ³⁷¹ ³⁷⁶ ³⁹⁹
Appropriately monitor and closely observe all patients who are started on citalopram therapy for clinical worsening, suicidality, or unusual changes in behavior; involve family members and/or caregivers in this process.³⁷⁰ ³⁷¹ ³⁷⁶ ³⁹⁹ (See Worsening of Depression and Suicidality Risk under Cautions.)

Introduction

Antidepressant; selective serotonin-reuptake inhibitor (SSRI).¹

Uses for Citalopram

Major Depressive Disorder

Management of major depressive disorder.¹ ⁶² ⁶⁹ ⁷⁸ ⁸⁹ ⁹⁹ ¹¹⁶ ¹¹⁷ ¹¹⁸ ¹¹⁹ ¹²⁰ ¹²¹ ¹²² ¹²³ ¹²⁴ ¹²⁵ ¹²⁶ ¹²⁷ ¹²⁸ ¹²⁹ ¹³⁰ ¹³¹ ¹³² ¹³³ ¹³⁴ ¹³⁵ ¹³⁶ ¹³⁷ ¹³⁸ ¹⁴⁰ ¹⁴¹ ¹⁴² ¹⁶³ ¹⁸⁷ ³⁴¹ ³⁶¹

Manufacturers state efficacy in hospital settings not established.¹ ³⁹⁹ However, efficacy has been demonstrated in hospitalized patients with depression, including severe depression,¹²⁴ ¹⁶² in several studies.⁶² ⁶⁹ ⁹⁹ ¹²⁰ ¹²¹ ¹²² ¹²³ ¹²⁴ ¹²⁵ ¹²⁶ ¹⁶²

APA states that effectiveness of antidepressants is generally comparable between and within classes of medications, including SSRIs, SNRIs, TCAs, MAO inhibitors, and other antidepressants (e.g., bupropion, mirtazapine, trazodone).^a Choose antidepressant based mainly on the following factors: patient preference; nature of prior response to medication; safety, tolerability, and anticipated adverse effects; concurrent psychiatric and medical conditions; specific properties of the medication (e.g., half-life, actions on CYP isoenzymes, other drug interactions); and cost.^a For most patients, an SSRI, SNRI, mirtazapine, or bupropion is considered optimal.^a Consult APA’s Practice Guidelines for the Treatment of Patients with Major Depressive Disorder for additional information.^a

Obsessive-Compulsive Disorder

Has been used in the management of obsessive-compulsive disorder^{† [off-label]}.¹⁷² ¹⁷³ ¹⁷⁴ ¹⁷⁵ ¹⁷⁶ ¹⁸³ ¹⁸⁴ ¹⁸⁶

Panic Disorder

Has been used in the management of panic disorder^{† [off-label]} with or without agoraphobia^{† [off-label]}.²⁸ ²⁹ ¹⁷⁴ ¹⁸⁹ ²⁸⁸ ²⁸⁹

Social Phobia

Has been used in the management of social phobia^{† [off-label]} (social anxiety disorder).³⁵⁰ ³⁵¹ ³⁵² ³⁵³ ³⁵⁴ ³⁵⁵

Alcohol Dependence

Has been used in the management of alcohol dependence^{† [off-label]}.⁴⁰ ⁴² ⁴³ ⁴⁴ ⁴⁵ ⁴⁶ ⁴⁷

Premenstrual Dysphoric Disorder

Has been used in the management of premenstrual dysphoric disorder^† (previously late luteal phase dysphoric disorder).¹⁸¹ ¹⁸²

Premature Ejaculation

Has been used for the management of premature ejaculation^†.²⁷³

May be less effective than some other SSRIs (e.g., paroxetine).²⁷³

Eating Disorders

Has been used in the management of bulimia nervosa^† or anorexia nervosa^† with equivocal efficacy.¹⁵ ¹⁶

Diabetic Neuropathy

Has been used in the management of diabetic neuropathy^†.²⁷⁹ ²⁸⁰

Posttraumatic Stress Disorder

Has been used in a limited number of adults with civilian- or combat-related posttraumatic stress disorder^† (PTSD).²⁸¹ ²⁸²

Citalopram Dosage and Administration

General

Allow at least 2 weeks to elapse between discontinuance of an MAO inhibitor intended to treat psychiatric disorders and initiation of citalopram, and vice versa.³⁹⁹ (See Contraindications and Serotonin Syndrome under Cautions and also see Specific Drugs under Interactions.)
Monitor for possible worsening of depression, suicidality, or unusual changes in behavior, especially at the beginning of therapy or during periods of dosage adjustments.³⁷⁰ ³⁷¹ ³⁷⁶ ³⁹⁹ (See Worsening of Depression and Suicidality Risk under Cautions.)
Correct hypokalemia and hypomagnesemia, if present, prior to initiating citalopram therapy; periodically monitor electrolytes during therapy as needed.³⁹⁹ ⁴¹⁶ (See QT-interval Prolongation and Torsades de Pointes under Cautions.)
Avoid abrupt discontinuance.¹³ ¹⁴ ¹⁷ ³⁹⁹ Taper dosage gradually and monitor for withdrawal symptoms.¹³ ¹⁴ ¹⁷ ³⁹⁹ ⁴⁰⁷ If intolerable symptoms occur following dosage reduction or discontinuance, consider reinstituting previously prescribed dosage, then resume more gradual dosage reductions.³⁹⁹ (See Withdrawal of Therapy under Cautions.)

Administration

Oral Administration

Administer orally once daily (morning or evening) without regard to meals.¹

Dosage

Available as citalopram hydrobromide; dosages expressed in terms of citalopram.¹

Adults

Major Depressive Disorder

Oral

Recommended initial dosage is 20 mg once daily, with an increase to a maximum dosage of 40 mg once daily at an interval of not <1 week.³⁹⁹ ⁴²⁴ Although prescribing information previously stated that certain patients may require 60 mg daily, dosages >40 mg once daily no longer are recommended because of risk of QT-interval prolongation and because they provide no additional therapeutic benefit.³⁹⁹ ⁴¹⁶ ⁴¹⁷ ⁴²⁴ (See QT-interval Prolongation and Torsades de Pointes under Cautions.)

Optimum duration not established; may require several months of therapy or longer.¹³ ¹⁰⁷ ¹⁰⁸ ¹⁰⁹ ¹¹⁰ ¹¹¹ ¹¹² ¹¹³ ¹⁸⁷ ³⁹⁹ Periodically reassess need for continued therapy.³⁹⁹

Obsessive-Compulsive Disorder†

Oral

Initially, 20 mg once daily.¹⁷² ¹⁷³ ¹⁷⁴ ¹⁸³ Gradually increase dosage according to clinical response.¹⁷² ¹⁷³ ¹⁷⁴ ¹⁸³

Maintenance dosages of 40–60 mg daily have been used;²¹ ¹⁷² ¹⁷³ ¹⁷⁴ ¹⁸³ however, dosages >40 mg once daily no longer recommended due to risk of QT-interval prolongation.³⁹⁹ ⁴¹⁶ ⁴¹⁷ ⁴²⁴ (See QT-interval Prolongation and Torsades de Pointes under Cautions.)

Panic Disorder†

Oral

Usual initial dosage: 10 mg daily.¹⁷⁴ Increase dosage after ≥1 week in 10- or 20-mg increments up to a dosage of 20–40 mg daily, depending on individual patient response and tolerability.²⁸ ²⁹ ¹⁷⁴ ²⁸⁸ ²⁸⁹

Usual maintenance dosage: 20–30 mg daily.²⁸ ²⁹ ²⁸⁹ Dosages >40 mg once daily no longer recommended due to risk of QT-interval prolongation.³⁹⁹ ⁴¹⁶ ⁴¹⁷ ⁴²⁴ (See QT-interval Prolongation and Torsades de Pointes under Cautions.)

Prescribing Limits

Adults

Oral

Maximum recommended dosage is 40 mg once daily.³⁹⁹ ⁴¹⁶ ⁴¹⁷ ⁴²⁴ (See QT-interval Prolongation and Torsades de Pointes under Cautions.)

Special Populations

Hepatic Impairment

Major Depressive Disorder

Oral

Maximum recommended dosage is 20 mg once daily.³⁹⁹ ⁴²⁴ (See QT-interval Prolongation and Torsades de Pointes under Cautions.)

Renal Impairment

Major Depressive Disorder

Oral

No dosage adjustment necessary in patients with mild to moderate renal impairment.¹ Dosage adjustment may not be necessary in patients with severe renal impairment, but caution is recommended.⁸⁸ ³⁹⁹ (See Elimination: Special Populations, under Pharmacokinetics.)

Geriatric Patients

In patients >60 years of age, maximum recommended dosage is 20 mg once daily.³⁹⁹ ⁴²⁴ (See QT-interval Prolongation and Torsades de Pointes under Cautions.)

Poor CYP2C19 Metabolizers or Patients Receiving CYP2C19 Inhibitors

Maximum recommended dosage is 20 mg once daily.³⁹⁹ ⁴¹⁶ ⁴²⁴ (See QT-interval Prolongation and Torsades de Pointes under Cautions and also see Interactions.)

Cautions for Citalopram

Contraindications

Citalopram is contraindicated in patients who are currently receiving or have recently (i.e., within 2 weeks) received therapy with an MAO inhibitor intended to treat psychiatric disorders.³⁹⁹ Conversely, MAO inhibitors intended to treat psychiatric disorders are contraindicated within 2 weeks of citalopram discontinuance.³⁹⁹ (See Serotonin Syndrome under Cautions and also see Specific Drugs under Interactions.)
Initiation of citalopram is contraindicated in patients receiving MAO inhibitors such as linezolid or IV methylene blue.³⁹⁹ (See Specific Drugs under Interactions.)
Concurrent pimozide therapy.¹ (See Interactions.)
Known hypersensitivity to citalopram, escitalopram, or any ingredient in the formulation.¹ ³⁴⁸ ³⁴⁹ ⁴⁰³

Warnings/Precautions

Warnings

Worsening of Depression and Suicidality Risk

Possible worsening of depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior in both adult and pediatric patients with major depressive disorder, whether or not they are taking antidepressants; may persist until clinically important remission occurs.³⁷⁰ ³⁷¹ ³⁷⁶ ³⁹⁹ However, suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide.³⁷⁰ ³⁷¹ ³⁷⁶

Appropriately monitor and closely observe patients receiving citalopram for any reason, particularly during initiation of therapy (i.e., the first few months) and during periods of dosage adjustments.³⁷⁰ ³⁷¹ ³⁷⁶ ³⁹⁹ (See Boxed Warning and also see Pediatric Use under Cautions.)

Anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and/or mania may be precursors to emerging suicidality.³⁷⁰ ³⁷⁶ ³⁹⁹ Consider changing or discontinuing therapy in patients whose depression is persistently worse or in those with emerging suicidality or symptoms that might be precursors to worsening depression or suicidality, particularly if severe, abrupt in onset, or not part of patient’s presenting symptoms.³⁷⁰ ³⁷¹ ³⁷⁶ ³⁹⁹ If decision is made to discontinue therapy, taper citalopram dosage as rapidly as is feasible but consider risks of abrupt discontinuance.³⁷⁰ ³⁹⁹ (See General under Dosage and Administration.)

Prescribe in smallest quantity consistent with good patient management to reduce risk of overdosage.³⁷⁰ ³⁹⁹

Observe these precautions for patients with psychiatric (e.g., major depressive disorder, obsessive-compulsive disorder) or nonpsychiatric disorders.³⁷⁰ ³⁹⁹

Sensitivity Reactions

Hypersensitivity Reactions

Possible anaphylaxis, allergic reactions, and angioedema.¹

If hypersensitivity reaction occurs, discontinue immediately and institute appropriate therapy as indicated.¹

Other Warnings and Precautions

QT-interval Prolongation and Torsades de Pointes

Causes dose-dependent QT_c-interval prolongation; postmarketing cases of torsades de pointes, ventricular tachycardia, and sudden death reported.³⁹⁹ ⁴¹⁶ ⁴¹⁷ ⁴¹⁸ ⁴¹⁹ ⁴²⁰ ⁴²¹ ⁴²⁴

Do not use citalopram dosages >40 mg daily.³⁹⁹ ⁴¹⁶ ⁴¹⁷ ⁴²⁴ Use not recommended in patients with congenital long QT syndrome, bradycardia, hypokalemia or hypomagnesemia, recent AMI, or uncompensated heart failure.³⁹⁹ ⁴²⁴ Do not use in patients receiving other drugs known to prolong the QT_c interval.³⁹⁹ ⁴²⁴ (See Interactions.)

Maximum dosage of 20 mg daily in patients who are poor metabolizers of CYP2C19 and in patients receiving a CYP2C19 inhibitor, patients with hepatic impairment, and in patients >60 years of age since higher citalopram exposures increase risk of QT-interval prolongation and torsades de pointes.³⁹⁹ ⁴²⁴

In patients at risk for clinically important electrolyte disturbances, obtain baseline and periodic serum potassium and magnesium measurements.³⁹⁹ ⁴²⁴ Correct hypokalemia and/or hypomagnesemia before citalopram administration because of increased risk of QT_c-interval prolongation and arrhythmias.³⁹⁹ ⁴¹⁶ ⁴²⁴ ECG monitoring recommended in patients in whom citalopram is not recommended but considered essential (e.g., patients with cardiac conditions mentioned above, those receiving other drugs known to prolong the QT_c interval).³⁹⁹ ⁴²⁴

Discontinue citalopram in patients with persistent QT_c measurements >500 msec.³⁹⁹ ⁴²⁴ If patient experiences symptoms indicating cardiac arrhythmias (e.g., dizziness, palpitations, syncope), initiate further evaluation, including cardiac monitoring.³⁹⁹ ⁴²⁴

Bipolar Disorder

May unmask bipolar disorder.¹ ³⁷⁰ (See Activation of Mania or Hypomania under Cautions.) Citalopram is not approved for use in treating bipolar depression.¹

Screen for risk of bipolar disorder by obtaining detailed psychiatric history (e.g., family history of suicide, bipolar disorder, depression) prior to initiating therapy.¹ ³⁷⁰

Serotonin Syndrome

Potentially life-threatening serotonin syndrome reported with SSRIs and SNRIs alone, but particularly during concurrent therapy with other serotonergic drugs (e.g., 5-HT₁ receptor agonists [“triptans”], TCAs, buspirone, fentanyl, lithium, tramadol, tryptophan, St. John's wort [Hypericum perforatum]) and with drugs that impair the metabolism of serotonin (particularly MAO inhibitors, both those used to treat psychiatric disorders and others, such as linezolid and methylene blue).²⁵³ ³¹⁶ ³¹⁷ ³⁸⁶ ³⁹⁹ ⁴⁰⁰ ⁴⁰⁸ (See Interactions.)

Symptoms of serotonin syndrome may include mental status changes (e.g., agitation, hallucinations, delirium, coma), autonomic instability (e.g., tachycardia, labile BP, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or GI symptoms (e.g., nausea, vomiting, diarrhea).³¹⁶ ³¹⁷ ³⁸⁶ ³⁹⁹ ⁴⁰⁰ ⁴⁰⁸

Citalopram is contraindicated in patients who are currently receiving or have recently (i.e., within 2 weeks) received therapy with MAO inhibitors intended to treat psychiatric disorders.³⁹⁹ Do not initiate citalopram in patients treated with other MAO inhibitors such as linezolid or IV methylene blue.³⁹⁹ (See Specific Drugs under Interactions.)

If concurrent therapy with other serotonergic drugs is clinically warranted, advise patient of potentially increased risk for serotonin syndrome, particularly during initiation of therapy and dosage increases.³⁹⁹

Monitor patients receiving citalopram for the development of serotonin syndrome.³⁹⁹ If manifestations occur, immediately discontinue citalopram and any concurrently administered serotonergic agents and initiate supportive and symptomatic treatment.³⁹⁹

Angle-closure Glaucoma

Pupillary dilation (mydriasis) occurs with many antidepressants, including citalopram, and may trigger an acute attack of angle-closure glaucoma (narrow-angle glaucoma) in patients with anatomically narrow angles who do not have a patent iridectomy.³⁹⁹ (See Advice to Patients.)

Withdrawal of Therapy

Withdrawal effects (e.g., dysphoric mood, irritability, agitation, dizziness, sensory disturbances [e.g., paresthesias, such as electric shock sensations], anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania) reported following discontinuance of serotonergic antidepressants, particularly when discontinuance was abrupt.¹⁷ ²¹² ²¹⁸ ²¹⁹ ²²⁰ ²²¹ ²²³ ²²⁴ ²²⁵ ²²⁶ ²²⁷ ²²⁸ ²²⁹ ²³⁰ ²³¹ ²³² ²³³ ²³⁴ ²³⁵ ³⁹⁹ Events generally self-limiting, but serious cases reported.¹⁷ ²⁰⁵ ²²⁵ ²²⁹ ²³⁰ ²³² ³⁹⁹

Abnormal Bleeding

Possible increased risk of bleeding with SSRIs, including citalopram, and SNRIs; events ranged from ecchymoses, hematomas, epistaxis, and petechiae to life-threatening hemorrhages.⁵⁴ ⁵⁵ ²⁰⁵ ²⁸³ ²⁸⁴ ²⁸⁵ ²⁸⁷ ³⁷⁷ ³⁷⁸ ³⁹⁹ Concomitant use of aspirin, NSAIAs, warfarin, or other anticoagulants may increase risk.⁵⁴ ⁵⁵ ³⁷⁷ ³⁹⁹ (See Drugs Affecting Hemostasis under Interactions and also see Advice to Patients.)

Hyponatremia/SIADH

Possible hyponatremia during treatment with SSRIs, including citalopram, and SNRIs; in many cases, hyponatremia appears to be due to SIADH.⁸ ⁹ ²⁰⁶ ²⁰⁷ ²⁰⁸ ³⁴⁴ ³⁶³ ³⁹⁹ Increased risk in patients who are volume depleted, elderly, or taking diuretics.²⁰¹ ²⁰² ²⁰³ ²⁰⁴ ²⁰⁵ ²⁰⁸ ²⁰⁹ ²¹⁰ ³⁴⁴ ³⁶³ ³⁹⁹ Initiate appropriate medical intervention and consider drug discontinuance in patients with symptomatic hyponatremia.³⁹⁹

Activation of Mania/Hypomania

Possible activation of mania/hypomania; use with caution in patients with a history of mania.¹ ²³⁶ ²³⁷ ³²⁷ (See Bipolar Disorder under Cautions.)

Seizures

Risk of seizures not systematically evaluated; use with caution in patients with a history of seizure disorder.¹

Cognitive/Motor Impairment

Citalopram did not impair intellectual function or psychomotor performance in healthy individuals.³⁹⁹ However, any psychoactive drug may impair judgment, thinking, or motor skills.³⁹⁹ (See Advice to Patients.)

Concomitant Disease

Limited experience with certain concurrent systemic diseases.³⁹⁹ (See QT-interval Prolongation and Torsades de Pointes under Cautions.)

Prescribing and Dispensing Precautions

Ensure accuracy of prescription; similarity in spelling of Celexa (citalopram hydrobromide), Celebrex (celecoxib), and Cerebyx (fosphenytoin sodium) may result in errors.³⁴⁶

Electroconvulsive Therapy (ECT)

Effects of concomitant use with ECT have not been systematically evaluated.¹

Specific Populations

Pregnancy

Category C.¹

Possible complications, sometimes severe and requiring prolonged hospitalization, respiratory support, enteral nutrition, and other forms of supportive care, reported in neonates exposed to citalopram, other SSRIs, or SNRIs late in the third trimester; may arise immediately upon delivery.²¹² ²¹³ ³⁸⁰ ³⁸¹ ³⁸² ³⁸³ ³⁹⁹ (See General under Dosage and Administration.)

Conflicting findings from available studies evaluating possible risk of persistent pulmonary hypertension of the newborn (PPHN) following in utero exposure to SSRIs; currently unclear whether SSRI use during pregnancy can cause PPHN.³⁹⁹ ⁶⁰⁰ ⁶⁰¹ ⁶⁰² ⁶⁰³ ⁶⁰⁴ ⁶⁰⁵ ⁶⁰⁶ ⁶¹⁰

Consult joint APA and ACOG guidelines (at [Web]) for additional information on management of depression in women prior to conception and during pregnancy, including treatment algorithms.⁶⁰⁰ ⁶⁰⁸

Effect on labor and delivery unknown.³⁹⁹

Lactation

Distributed into milk;¹ ⁵ ⁶ ⁹⁰ ⁹¹ ⁹² ⁹⁵ ⁹⁶ ³⁶² possible serious adverse reactions (e.g., excessive somnolence, decreased feeding, weight loss) in nursing infants.¹ Discontinue nursing or the drug.¹

Pediatric Use

Safety and efficacy not established in children <18 years of age.¹ Results of 2 placebo-controlled trials in children and adolescents with major depressive disorder did not support a claim of efficacy for use of citalopram in pediatric patients with this condition.¹ ³⁷⁹

FDA warns that a greater risk of suicidal thinking or behavior (suicidality) occurred during the first few months of antidepressant treatment compared with placebo in children and adolescents with major depressive disorder, obsessive-compulsive disorder (OCD), or other psychiatric disorders based on pooled analyses of 24 short-term, placebo-controlled trials of 9 antidepressant drugs (SSRIs and others).³⁷⁰ ³⁷¹ However, a more recent meta-analysis of 27 placebo-controlled trials of 9 antidepressants (SSRIs and others) in patients <19 years of age with major depressive disorder, OCD, or non-OCD anxiety disorders suggests that the benefits of antidepressant therapy in treating these conditions may outweigh the risks of suicidal behavior or suicidal ideation.³⁹⁸ No suicides occurred in these pediatric trials.³⁷⁰ ³⁹⁸ ³⁹⁹

Carefully consider these findings when assessing potential benefits and risks of citalopram in a child or adolescent for any clinical use.¹ ³⁷⁰ ³⁷¹ ³⁷⁶ ³⁹⁸ ³⁹⁹ (See Suicidality in the Boxed Warning and also see Worsening of Depression and Suicidality Risk under Cautions.)

Decreased appetite and weight loss observed with use of SSRIs; monitor weight and growth regularly in children and adolescents treated with long-term citalopram therapy.³⁹⁹

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults.³⁹⁹

Higher citalopram exposures may increase risk of QT-interval prolongation and torsades de pointes.⁸³ ⁸⁵ ³⁹⁹ ⁴²⁴ (See Geriatric Patients under Dosage and Administration and also see Special Populations under Pharmacokinetics.)

Clinically important hyponatremia reported in geriatric patients, who may be at increased risk for this adverse effect.²⁰¹ ²⁰² ²⁰³ ²⁰⁴ ²⁰⁵ ²⁰⁸ ²⁰⁹ ²¹⁰ ³⁴⁴ ³⁶³ ³⁹⁹ Some clinicians recommend periodic monitoring (especially during the first several months) of serum sodium concentrations in geriatric patients receiving SSRIs.²⁰⁷ ²⁰⁸ ²⁰⁹ ³⁴⁴ ³⁴⁸ ³⁴⁹ (See Hyponatremia/SIADH under Cautions.)

In pooled data analyses, a reduced risk of suicidality was observed in adults ≥65 years of age with antidepressant therapy compared with placebo.³⁷⁰ ³⁷¹ ³⁹⁹ (See Boxed Warning and also see Worsening of Depression and Suicidality Risk under Cautions.)

Hepatic Impairment

Higher citalopram exposures may increase risk of QT-interval prolongation and torsades de pointes.¹ ⁴ ³⁹⁹ ⁴²⁴ Use with caution.³⁹⁹ ⁴²⁴ (See Hepatic Impairment under Dosage and Administration and also see Elimination: Special Populations, under Pharmacokinetics.)

Renal Impairment

Use with caution in patients with severe renal impairment.¹ ⁴ (See Renal Impairment under Dosage and Administration and also see Elimination: Special Populations, under Pharmacokinetics.)

Common Adverse Effects

Nausea, dry mouth, insomnia, sweating, sexual dysfunction (ejaculatory disorder, impotence, decreased libido), tremor, diarrhea, somnolence, dyspepsia, fatigue, upper respiratory tract infection, rhinitis.¹

Drug Interactions

Extensively metabolized in liver, principally by CYP2C19 and 3A4.²⁷⁸ ³⁹⁹ Does not inhibit CYP2C9, 2E1, or 3A4 in vitro and exhibits only weak inhibition against CYP1A2, CYP2D6, and CYP2C19.¹ ² ³ ¹⁷⁰ ²⁷⁸

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of 3A4: Clinically important pharmacokinetic interaction unlikely.³⁹⁹

Inhibitors of CYP2C19: Risk of QT-interval prolongation; maximum recommended dosage is 20 mg once daily in patients concurrently receiving cimetidine or another CYP2C19 inhibitor.³⁹⁹ ⁴¹⁶ ⁴²⁴

Drugs Metabolized by Hepatic Microsomal Enzymes

Substrates of CYP1A2, CYP2D6, and CYP2C19: Citalopram expected to have little in vivo effect on substrate metabolism; however, clinical importance unknown.¹

Drugs that Prolong the QT Interval

Citalopram use not recommended in patients concurrently receiving other drugs known to prolong the QT_c interval.³⁹⁹ ⁴²⁴ If such use considered essential, ECG monitoring recommended.³⁹⁹ ⁴²⁴ (See QT-interval Prolongation and Torsades de Pointes under Cautions.)

Drugs Affecting Hemostasis

Potential pharmacologic interaction (increased risk of bleeding) with concomitant use of drugs that affect hemostasis.⁵⁴ ⁵⁵ ³⁷⁷ ³⁹⁹ Use with caution.³⁹⁹ (See Abnormal Bleeding under Cautions.)

Drugs Associated with Serotonin Syndrome

Potentially life-threatening serotonin syndrome with other serotonergic drugs.²⁰⁵ ²⁹¹ ²⁹² ²⁹³ ²⁹⁴ ²⁹⁵ ²⁹⁶ ²⁹⁷ ³¹² ³¹⁴ ³¹⁵ ³¹⁶ ³¹⁷ ³⁸⁶ ³⁹⁹ If concomitant use of other serotonergic drugs with citalopram is clinically warranted, advise patients of the increased risk for serotonin syndrome, particularly during treatment initiation and dosage increases.³⁹⁹

If serotonin syndrome occurs, immediately discontinue citalopram and any concurrently administered serotonergic agents; initiate supportive and symptomatic treatment.³⁹⁹ (See Serotonin Syndrome under Cautions.)

Specific Drugs

Drug	Interaction	Comment
Alcohol	Did not potentiate cognitive and motor effects of alcohol in one study;¹ possible serotonergically mediated pharmacodynamic interaction in CNS²⁰ ³⁴ ³⁵ ³⁶ ³⁷ ³⁸ ³⁹ ⁴⁰ ⁴⁴ ⁴⁵ ⁴⁶ ⁴⁷	Concomitant use not recommended¹
Antiarrhythmic agents, class IA (e.g., quinidine, procainamide) and class III (e.g., amiodarone, sotalol)	Increased risk of QT_c-interval prolongation³⁹⁹ ⁴²⁴	Avoid concomitant use;³⁹⁹ ⁴²⁴ if concurrent use considered essential, monitor ECG³⁹⁹ ⁴²⁴
Antidepressants, other SSRIs (e.g., escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) or SNRIs (e.g., desvenlafaxine, duloxetine, milnacipran, venlafaxine)	Potentially life-threatening serotonin syndrome³⁹⁹	If concomitant use clinically warranted, advise patients of the increased risk for serotonin syndrome, particularly during treatment initiation and dosage increases³⁹⁹ If serotonin syndrome occurs, immediately discontinue citalopram, the SSRI or SNRI, and any concurrently administered serotonergic agents; initiate supportive and symptomatic treatment³⁹⁹
Antidepressants, tricyclics (TCAs) (e.g., desipramine, imipramine)	Possible increased plasma TCA concentrations with TCAs that are substrates of CYP2D6¹ ⁴⁰³ Potentially life-threatening serotonin syndrome³⁹⁹	Use with caution¹ If concomitant use clinically warranted, advise patients of the increased risk for serotonin syndrome, particularly during treatment initiation and dosage increases³⁹⁹ If serotonin syndrome occurs, immediately discontinue citalopram, the TCA, and any concurrently administered serotonergic agents; initiate supportive and symptomatic treatment³⁹⁹
Antipsychotic agents (e.g., chlorpromazine, clozapine, pimozide, thioridazine)	Increased risk of QT_c-interval prolongation³⁹⁹ ⁴²⁴ Clozapine: Substantial increases in trough plasma clozapine concentrations reported with concomitant citalopram⁴⁰² Pimozide: Increased risk of QT_c-interval prolongation;³⁹⁹ pharmacokinetic interactions unlikely³⁹⁹	Antipsychotics that prolong QT interval (e.g., chlorpromazine, thioridazine): Avoid concomitant use;³⁹⁹ ⁴²⁴ if concurrent use considered essential, monitor ECG³⁹⁹ ⁴²⁴ Clozapine: Caution advised; monitor closely and consider reduction in clozapine dosage if used concomitantly⁴⁰² Pimozide: Concomitant use contraindicated³⁹⁹
Buspirone	Potentially life-threatening serotonin syndrome³⁹⁹	If concomitant use clinically warranted, advise patients of the increased risk for serotonin syndrome, particularly during treatment initiation and dosage increases³⁹⁹ If serotonin syndrome occurs, immediately discontinue citalopram, buspirone, and any concurrently administered serotonergic agents; initiate supportive and symptomatic treatment³⁹⁹
Carbamazepine	Possible increased citalopram clearance¹ ³³⁶ ³³⁷ ³⁴⁸ ³⁴⁹
Cimetidine	Increased citalopram AUC and peak plasma concentrations¹ ⁷	Maximum recommended citalopram dosage is 20 mg daily due to risk of QT-interval prolongation³⁹⁹ ⁴¹⁶ ⁴²⁴
CNS drugs	Potentially additive CNS effects¹	Use with caution¹
Cyclosporine	Pharmacokinetic interaction unlikely³²⁶
Digoxin	Pharmacokinetic interaction unlikely¹ ¹⁸⁸
Diuretics	Possible increased risk of hyponatremia³⁹⁹
Escitalopram	Therapeutic duplication; escitalopram is the more active isomer of racemic citalopram⁴⁰³ Potentially life-threatening serotonin syndrome³⁹⁹	Concomitant use not recommended³⁹⁹ ⁴⁰³
Fentanyl	Potentially life-threatening serotonin syndrome³⁹⁹	If concomitant use clinically warranted, advise patients of the increased risk for serotonin syndrome, particularly during treatment initiation and dosage increases³⁹⁹ If serotonin syndrome occurs, immediately discontinue citalopram, fentanyl, and any concurrently administered serotonergic agents; initiate supportive and symptomatic treatment³⁹⁹
Gatifloxacin	Increased risk of QT_c-interval prolongation³⁹⁹ ⁴²⁴	Avoid concomitant use;³⁹⁹ ⁴²⁴ if concurrent use considered essential, monitor ECG³⁹⁹ ⁴²⁴
5-HT₁ receptor agonists (triptans; e.g., almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan)	Potentially life-threatening serotonin syndrome²⁰⁵ ²⁹⁴ ³⁰⁴ ³⁸⁶ ³⁹⁹	If concomitant use clinically warranted, advise patients of the increased risk for serotonin syndrome, particularly during treatment initiation and dosage increases³⁹⁹ If serotonin syndrome occurs, immediately discontinue citalopram, the triptan, and any concurrently administered serotonergic agents; initiate supportive and symptomatic treatment³⁹⁹
Isoniazid	Potentially life-threatening serotonin syndrome³²⁰
Ketoconazole	Decreased peak concentrations and AUC of ketoconazole;³²⁵ ³⁹⁹ pharmacokinetics of citalopram and demethylcitalopram not substantially affected³²⁵ ³⁹⁹	Routine citalopram dosage adjustment not necessary³²⁵
Linezolid	Potentially life-threatening serotonin syndrome³⁹⁶ ³⁹⁹ ⁴¹¹ ⁴¹² ⁴¹³ ⁴¹⁴ ⁴¹⁵ ⁶¹¹ ⁶¹²	Do not use concurrently;⁶¹¹ consider availability of alternative anti-infectives and weigh benefit of linezolid against risk of serotonin syndrome³⁹⁹ ⁶¹¹ If emergency use of linezolid is considered necessary, immediately discontinue citalopram; monitor closely for symptoms of serotonin syndrome for 2 weeks or until 24 hours after the last linezolid dose, whichever comes first³⁹⁹ ⁶¹¹ May resume citalopram 24 hours after last linezolid dose³⁹⁹ ⁶¹¹ If nonemergency use of linezolid is planned, withhold citalopram for at least 2 weeks prior to initiating linezolid⁶¹¹ Do not initiate citalopram in patients receiving linezolid³⁹⁹ ⁶¹¹ If urgent treatment of a psychiatric condition is necessary, consider other interventions, including hospitalization; may initiate citalopram 24 hours after last linezolid dose³⁹⁹ ⁶¹¹
Lithium	Potentially life-threatening serotonin syndrome¹⁶⁹ ³⁹⁹ Pharmacokinetic interaction unlikely¹⁶⁸	If concomitant use clinically warranted, exercise caution and advise patients of the increased risk for serotonin syndrome, particularly during treatment initiation and dosage increases³⁹⁹ If serotonin syndrome occurs, immediately discontinue citalopram, lithium, and any concurrently administered serotonergic agents; initiate supportive and symptomatic treatment³⁹⁹ Monitor serum lithium concentrations; adjust dosage accordingly¹
MAO inhibitors	Potentially life-threatening serotonin syndrome³¹⁶ ³¹⁷ ³¹⁸ ³⁹⁹ ⁴⁰³	Concomitant use contraindicated³⁹⁹ Allow at least 2 weeks to elapse between discontinuance of an MAO inhibitor intended to treat psychiatric disorders and initiation of citalopram, and vice versa³⁹⁹
Methadone	Increased risk of QT_c-interval prolongation³⁹⁹ ⁴²⁴	Avoid concomitant use;³⁹⁹ ⁴²⁴ if concurrent use considered essential, monitor ECG³⁹⁹ ⁴²⁴
Methylene blue	Potentially life-threatening serotonin syndrome³⁹⁹ ⁶¹³ ⁶¹⁴ Most cases occurred when methylene blue was used as a diagnostic (visualizing) dye^† (1–8 mg/kg IV) during parathyroid surgery; unclear whether there is a risk of serotonin syndrome when methylene blue is administered by other routes or in lower IV doses in patients receiving serotonergic drugs³⁹⁹ ⁶¹³ ⁶¹⁴	Generally should not use methylene blue in patients receiving citalopram;⁶¹³ consider availability of alternative interventions and weigh benefits of IV methylene blue against risk of serotonin syndrome³⁹⁹ ⁶¹³ If emergency use of IV methylene blue is considered necessary, immediately discontinue citalopram and monitor for symptoms of serotonin syndrome for 2 weeks or until 24 hours after last methylene blue dose, whichever comes first³⁹⁹ ⁶¹³ May resume citalopram 24 hours after last dose of IV methylene blue³⁹⁹ ⁶¹³ If nonemergency use of methylene blue is planned, withhold citalopram for at least 2 weeks prior to initiating methylene blue⁶¹³ Do not initiate citalopram in patients receiving IV methylene blue³⁹⁹ ⁶¹³ If urgent treatment of a psychiatric condition is necessary, consider other interventions, including hospitalization; may initiate citalopram 24 hours after last IV methylene blue dose³⁹⁹ ⁶¹³
Metoprolol	Increased plasma metoprolol concentrations possibly resulting in decreased cardioselectivity¹
Moxifloxacin	Increased risk of QT_c-interval prolongation³⁹⁹ ⁴²⁴	Avoid concomitant use;³⁹⁹ ⁴²⁴ if concurrent use considered essential, monitor ECG³⁹⁹ ⁴²⁴
NSAIAs (e.g., aspirin)	Increased risk of bleeding¹ ⁵⁴ ⁵⁵ ³⁷⁷ ³⁷⁸ ⁴⁰³	Use with caution¹ ⁴⁰³
Pentamidine	Increased risk of QT_c-interval prolongation³⁹⁹ ⁴²⁴	Avoid concomitant use;³⁹⁹ ⁴²⁴ if concurrent use considered essential, monitor ECG³⁹⁹ ⁴²⁴
Ritonavir	Pharmacokinetic interactions unlikely⁴⁰³
Selegiline	Potentially life-threatening serotonin syndrome²⁹⁴ ²⁹⁶ ³¹⁹	Avoid concomitant use³⁰³ ³¹⁹ Allow at least 2 weeks to elapse between discontinuance of selegiline and initiation of citalopram, or vice versa³⁰³ ³¹⁹
St. John's wort (Hypericum perforatum)	Potentially life-threatening serotonin syndrome³⁹⁹	If concomitant use clinically warranted, advise patients of the increased risk for serotonin syndrome, particularly during treatment initiation and dosage increases³⁹⁹ If serotonin syndrome occurs, immediately discontinue citalopram, St. John's wort, and any concurrently administered serotonergic agents; initiate supportive and symptomatic treatment³⁹⁹
Theophylline	No effects evident on theophylline pharmacokinetics ¹ ³²⁹
Tramadol	Potentially life-threatening serotonin syndrome³⁹⁹	If concomitant use clinically warranted, advise patients of the increased risk for serotonin syndrome, particularly during treatment initiation and dosage increases³⁹⁹ If serotonin syndrome occurs, immediately discontinue citalopram, tramadol, and any concurrently administered serotonergic agents; initiate supportive and symptomatic treatment³⁹⁹
Triazolam	Pharmacokinetic interactions unlikely¹ ³¹⁶ ³²⁸
Tryptophan	Potentially life-threatening serotonin syndrome²⁰⁵ ³⁹⁹	If concomitant use clinically warranted, advise patients of the increased risk for serotonin syndrome, particularly during treatment initiation and dosage increases³⁹⁹ If serotonin syndrome occurs, immediately discontinue citalopram, tryptophan, and any concurrently administered serotonergic agents; initiate supportive and symptomatic treatment³⁹⁹
Warfarin	Possible increased PT and risk of bleeding¹⁹⁰ ³⁹⁹ Pharmacokinetic interactions unlikely¹⁹⁰ ³⁹⁹	Carefully monitor patients receiving warfarin during initiation and discontinuance of citalopram therapy³⁹⁹

Citalopram Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral administration,¹ ¹⁸ ⁶² ⁸⁰ ⁸² ⁹⁷ ¹⁰⁰ ¹⁰¹ ³³⁹ with peak plasma concentration usually attained within 4 hours.¹ ³⁴⁹

Absolute oral bioavailability is approximately 80%.¹ ⁴

Commercially available tablets and oral solution reportedly are bioequivalent.⁶¹⁵

Onset

Antidepressant effect usually occurs within 1–4 weeks.¹ ¹⁷⁴

Food

Food does not affect absorption.¹

Special Populations

In geriatric patients ≥60 years of age, AUC is increased by 23–30%.⁸³ ⁸⁵ ³⁹⁹

Poor metabolizers of CYP2C19: peak steady-state concentrations and AUCs increased by 68 and 107%, respectively.³⁹⁹

Steady-state citalopram concentrations not substantially different in healthy individuals with poor or extensive CYP2D6 metabolizer phenotypes.²⁷⁸ ³⁹⁹

Distribution

Extent

Apparently widely distributed in body tissues.¹⁸ ⁶² ⁸⁰ ⁸² ⁹⁷ ³³⁹

Crosses blood-brain barrier.⁶² ⁸⁶ ⁸⁷

Crosses the placenta.⁹⁵ ³⁶² ⁴⁰¹

Distributed into breast milk.¹ ⁵ ⁶ ⁹⁰ ⁹¹ ⁹² ⁹⁵ ⁹⁶ ³⁶²

Plasma Protein Binding

Approximately 80%.¹ ³⁴⁹

Elimination

Metabolism

Extensively metabolized in the liver to less pharmacologically active metabolites by multiple enzyme systems, including CYP3A4 and CYP2C19.¹ ⁷⁷ ⁹⁷ ²⁷⁸

Elimination Route

Excreted principally in urine (75%) and feces (10%).¹⁰⁰

Half-life

Approximately 35 hours.⁴ ⁶² ⁸⁰ ⁸² ⁸³ ³³⁹

Special Populations

In geriatric patients ≥60 years of age, half-life is increased by 30–50%.⁸³ ³⁹⁹

Hepatic impairment decreases oral clearance by 37% and doubles half-life.¹ ⁴

Mild to moderate renal impairment decreases oral clearance by 17%.¹ Severe renal impairment did not substantially alter pharmacokinetics in one study.⁸⁸

Stability

Storage

Oral

Solution

20–25°C (may be exposed to 15–30°C).⁶¹⁵

Tablets

25°C (may be exposed to 15–30°C).¹ ¹⁹

Actions

Racemic (50:50) mixture of the R- and S-enantiomers; inhibition of serotonin (5-HT) reuptake primarily due to the S-enantiomer (escitalopram).¹ ¹⁸ ²⁰ ⁹⁷
Mechanism of action as an antidepressant is presumed to be linked to potentiation of serotonergic activity in the CNS resulting from its inhibition of CNS neuronal reuptake of 5-HT.¹ ²⁰
Highly selective SSRI with minimal effects on norepinephrine (NE) and dopamine (DA) neuronal reuptake and no or very low affinity for 5-HT_1A, 5-HT_2A, dopamine D₁ and D₂, α₁-, α₂-, and β-adrenergic, histamine (H₁), GABA, muscarinic cholinergic, and benzodiazepine receptors.¹ ¹⁸ ²⁰ ²⁶ ⁵²

Advice to Patients

Importance of providing copy of written patient information (medication guide) each time citalopram is dispensed.³⁷⁰ ³⁷¹ ³⁷⁶ ³⁹⁹ Importance of advising patients to read the patient information before taking citalopram and each time the prescription is filled.³⁹⁹
Risk of suicidality; importance of patients, caregivers, and families being alert to and immediately reporting emergence of suicidality, worsening depression, or unusual changes in behavior, especially during the first few months of therapy or during periods of dosage adjustment.³⁷⁰ ³⁷¹ ³⁷⁶ ³⁹⁹ (See Worsening of Depression and Suicidality Risk under Cautions.)
Potential risk of serotonin syndrome, particularly with concurrent use of citalopram and 5-HT₁ receptor agonists (also called triptans), tramadol, tryptophan, other serotonergic agents, or antipsychotic agents.³⁸⁶ ³⁹⁹ Importance of immediately contacting clinician if manifestations of serotonin syndrome develop (e.g., restlessness, hallucinations, delirium, loss of coordination, fast heart beat, increased body temperature, sweating, muscle stiffness, labile BP, diarrhea, coma, nausea, vomiting, confusion).³⁸⁶ ³⁹⁹
Importance of instructing patients not to take citalopram with an MAO inhibitor or within 14 days of stopping the drug, and vice versa.³⁹⁹
Risk of QT prolongation and torsades de pointes.³⁹⁹ ⁴²⁴ Importance of immediately contacting clinician if signs and symptoms of QT prolongation develop (e.g., chest pain, palpitations, bradycardia or tachycardia, shortness of breath, dizziness or fainting).³⁹⁹ ⁴²⁴
Risk of cognitive and motor impairment; importance of exercising caution while operating hazardous machinery, including automobile driving, until patients gain experience with the drug’s effects.³⁹⁹
Importance of patients being aware that withdrawal effects may occur when stopping citalopram, especially with abrupt discontinuance of the drug.³⁹⁹
Importance of informing patients that if they receive diuretics, are otherwise volume depleted, or are elderly, that they may be at greater risk of developing hyponatremia during citalopram therapy.³⁹⁹
Importance of avoiding alcohol during citalopram therapy.³⁹⁹
Importance of advising patients that citalopram can cause mild pupillary dilation, which can lead to an episode of angle-closure glaucoma in susceptible individuals.³⁹⁹ Possible symptoms include eye pain, vision changes, and swelling or redness in or around the eye.³⁹⁹ Preexisting glaucoma is almost always open-angle glaucoma since angle-closure glaucoma can be treated definitively with iridectomy when diagnosed; open-angle glaucoma is not a risk factor for angle-closure glaucoma.³⁹⁹ Patients may wish to be examined to determine whether they are susceptible to angle-closure glaucoma and have a prophylactic procedure (e.g., iridectomy) if they are susceptible.³⁹⁹
Importance of continuing citalopram therapy even if a response is not evident within 1–4 weeks, unless directed otherwise.¹
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription (e.g., pimozide, MAO inhibitors) and OTC drugs or herbal supplements, as well as any concomitant illnesses (e.g., cardiovascular disease [especially congenital long QT syndrome], liver disease, kidney disease, seizure disorder) or personal or family history of suicidality or bipolar disorder.³⁹⁹ Importance of advising patients about the risk of bleeding associated with concomitant use of citalopram with aspirin or other NSAIAs, warfarin, or other drugs that affect coagulation.³⁹⁹
Importance of informing patients of other important precautionary information.¹ (See Cautions.)

Preparations

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

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

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

Citalopram Hydrobromide
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, film-coated	10 mg (of citalopram)*	CeleXA	Forest
			Citalopram Hydrobromide Tablets
		20 mg (of citalopram)*	CeleXA (scored)	Forest
			Citalopram Hydrobromide Tablets
		40 mg (of citalopram)*	CeleXA (scored)	Forest
			Citalopram Hydrobromide Tablets
	Solution	10 mg (of citalopram) per 5 mL*	Citalopram Hydrobromide Oral Solution

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

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