Skip to Content

Citalopram

Medically reviewed on Nov 15, 2018

Pronunciation

See also: Ingrezza

(sye TAL oh pram)

Index Terms

  • Citalopram Hydrobromide
  • Nitalapram

Dosage Forms

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

Solution, Oral:

Generic: 10 mg/5 mL (240 mL)

Tablet, Oral:

CeleXA: 10 mg

CeleXA: 20 mg, 40 mg [scored]

Generic: 10 mg, 20 mg, 40 mg

Brand Names: U.S.

  • CeleXA

Pharmacologic Category

  • Antidepressant, Selective Serotonin Reuptake Inhibitor

Pharmacology

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.

Distribution

Vd: 12 L/kg

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

Excretion

Urine (Citalopram 10% and DCT 5%)

Note: Clearance was decreased, while half-life was significantly increased in patients with hepatic impairment. Mild to moderate renal impairment may reduce clearance (17%) and prolong half-life of citalopram. No pharmacokinetic information is available concerning patients with severe renal impairment. AUC and half-life were significantly increased in elderly patients (≥60 years), and in poor CYP2C19 metabolizers, steady state Cmax and AUC was increased by 68% and 107%, respectively.

Onset of Action

Depression: The onset of action is 1 to 4 weeks; however, individual response varies greatly and full response may not be seen until 8 to 12 weeks after initiation of treatment.

Time to Peak

Serum: 1 to 6 hours, average within 4 hours

Duration of Action

1 to 2 days

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)

Protein Binding

Plasma: ~80%

Special Populations: Renal Function Impairment

Oral clearance decreased 17% in mild to moderate renal impairment.

Special Populations: Hepatic Function Impairment

Oral clearance decreased 37% and half-life doubled in reduced hepatic function.

Special Populations: Elderly

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

Special Populations: Gender

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

Use: Labeled Indications

Major depressive disorder (unipolar): Treatment of unipolar major depressive disorder

Off Label Uses

Aggressive or agitated behavior associated with dementia

Data from a randomized, double-blind, placebo-controlled study support the use of citalopram in the treatment of agitation associated with dementia [Porsteinsson 2014].

Binge eating disorder

Data from a limited number of patients studied suggest that citalopram may be beneficial for the treatment of binge eating disorder by reducing binge episode frequency, weight, and severity of illness; however, average doses used (>40 mg) are no longer recommended due to an increased risk of cardiovascular effects [McElroy 2003].

Based on the American Psychiatric Association practice guideline for the treatment of patients with eating disorders and World Federation of Societies of Biological Psychiatry guidelines for the treatment of the pharmacologic treatment of eating disorders, citalopram given for binge eating disorder is effective and recommended; however, these guidelines were drafted prior to changes in the citalopram labeling regarding dose-related QT prolongation.

Bulimia nervosa

Data from one small, randomized, active-controlled trial and another study of lower quality (open-label, nonrandomized study) in patients with bulimia nervosa suggest that citalopram may be beneficial for the treatment of bulimia nervosa [Calandra 1999], [Leombruni 2006].

Generalized anxiety disorder

Data from a limited number of adult and geriatric patients suggest that citalopram may be beneficial for the treatment of generalized anxiety disorder [Blank 2006], [Lenze 2005], [Varia 2002].

Obsessive-compulsive disorder (adults)

Data from a randomized, double-blind, placebo-controlled study support the use of citalopram in the treatment of OCD [Montgomery 2001].

Based on the American Psychiatric Association practice guideline for the treatment of patients with obsessive-compulsive disorder, the use of an SSRI, such as citalopram, is an effective and recommended treatment option for patients with this condition.

Obsessive-compulsive disorder (children/adolescents)

Data from 3 open-label trials in children and adolescents (ages 6 to 18 years) with OCD suggest that citalopram may be beneficial for the treatment of children and adolescents with this condition [Mukaddes 2003], [Thomsen 2001], [Thomsen 1997].

Panic disorder

Data from 3 double-blind, randomized, parallel-group, placebo-controlled, multicenter studies and 2 single-blind, flexible-dose studies support the use of citalopram in the treatment of panic disorder [Leinonen 2000], [Perna 2001], [Seedat 2003], [Stahl 2003], [Wade 1997].

Based on the American Psychiatric Association guidelines for the treatment of patients with panic disorder and the World Federation of Societies of Biological Psychiatry guidelines for the pharmacological treatment of anxiety, obsessive-compulsive, and posttraumatic stress disorders, citalopram is effective and recommended in the management of panic disorder.

Posttraumatic stress disorder

Data from a double-blind, randomized, placebo- and active-controlled trial and an open-label study suggest that the use of citalopram may be beneficial in the treatment of PTSD [English 2006], [Tucker 2003].

Based on the American Psychiatric Association guidelines for the treatment of patients with acute stress disorder and PTSD and the World Federation of Societies of Biological Psychiatry guidelines for the pharmacological treatment of anxiety, obsessive-compulsive, and posttraumatic stress disorders, SSRIs are effective and recommended as first-line treatment for PTSD. The guidelines provide no recommendations specific to citalopram because at the time of publication controlled studies with citalopram were not available; however, clinical consensus suggests SSRIs are equivalent in efficacy.

Premature ejaculation

Data from a limited number of patients in controlled trials suggest that citalopram may be beneficial for the treatment of premature ejaculation [Atmaca 2002a], [Safarinejad 2006].

According to the International Society for Sexual Medicine guidelines, citalopram is effective and recommended in the management of premature ejaculation; however, paroxetine may have a more robust effect.

Premenstrual dysphoric disorder

Data from a limited number of patients studied suggest that citalopram may be beneficial for the treatment of premenstrual dysphoric disorder as a continuous daily dose or during the luteal phase [Wikander 1998].

Based on the International Society for Premenstrual Disorders auditable standards for diagnosis and management of premenstrual disorder, SSRIs are effective and recommended in the management of premenstrual dysphoric disorder.

Social anxiety disorder

Data from a limited number of clinical trials suggest that citalopram may be beneficial for the treatment of social anxiety disorder [Atmaca 2002b], [Furmark 2005].

Based on the World Federation of Societies of Biological Psychiatry guidelines for the pharmacological treatment of anxiety, obsessive-compulsive, and posttraumatic stress disorders, SSRIs such as citalopram are effective and recommended for the management of social anxiety disorder.

Vasomotor symptoms associated with menopause

Data from 2 randomized, placebo-controlled trials and a meta-analysis support the use of citalopram in the treatment of vasomotor symptoms (eg, hot flashes) in peri- or postmenopausal women [Barton 2010], [Kalay 2007], [Shams 2014].

Based on the American Association of Clinical Endocrinologists and American College of Endocrinology position statement on menopause, the Endocrine Society guideline on the treatment of symptoms of menopause, and the North American Menopause Society position statement on nonhormonal management of menopause-associated vasomotor symptoms, SSRIs (including citalopram) are an effective and recommended alternative for the management of vasomotor symptoms associated with menopause in patients with contraindications to hormonal therapy or who prefer not to use hormonal therapy. Based on the American Cancer Society/American Society of Clinical Oncology breast cancer survivorship care guideline, SSRIs may be used to help mitigate vasomotor symptoms of premature menopause in women previously treated for breast cancer.

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

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, patients with significant hepatic impairment, and patients who are concurrently receiving medications that significantly increase citalopram levels (eg, cimetidine, omeprazole, voriconazole) or who are known poor metabolizers of CYP2C19 substrates (manufacturer’s labeling). 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 (Hirsch 2018c; WFSBP [Bandelow 2012]).

Aggressive or agitated behavior associated with dementia (off-label use): Based on limited data: Oral: Adults <60 years of age: Initial: 10 mg once daily; increase to 20 mg once daily after ≥3 days. Some patients who do not satisfactorily respond to a trial of 20 mg/day may benefit by titrating to 30 mg/day (Pollock 2002; Pollock 2007; Porsteinsson 2014). Adults ≥60 years of age: Maximum dose: 20 mg/day.

Binge eating disorder (off-label use): Based on limited data: Oral: Adults <60 years of age: Initial: 20 mg once daily; may increase dose based on response and tolerability at intervals ≥1 week to 40 mg once daily (McElroy 2003). Although doses up to 60 mg/day have been studied, due to safety considerations the recommended maximum dose is 40 mg/day. Adults ≥60 years of age: Maximum dose: 20 mg/day.

Bulimia nervosa (alternative agent) (off-label use): Note: Some experts recommend against use of citalopram for bulimia nervosa due cardiac safety concerns, particularly with electrolyte disturbances that can occur in bulimia nervosa. Fluoxetine may be a better treatment option based on efficacy and tolerability (Crow 2018). Oral: Adults <60 years of age: Initial: 20 mg once daily; may gradually increase dose (eg, intervals ≥1 week) based on response and tolerability in increments of 10 mg to a maximum dose of 40 mg/day (Calandra 1999; Leombruni 2006). Adults ≥60 years of age: Maximum dose: 20 mg/day.

Generalized anxiety disorder (off-label use): Oral: Adults <60 years of age: Initial: 10 mg once daily; may gradually increase dose based on response and tolerability in 10 mg increments at intervals ≥1 week up to a maximum dose of 40 mg/day (Blank 2006; Varia 2002). Adults ≥60 years of age: Maximum dose: 20 mg/day.

Major depressive disorder (unipolar): Adults <60 years of age: Oral: Initial: 20 mg once daily; increase dose at intervals ≥1 week up to a maximum dose of 40 mg/day. Doses >40 mg/day have not demonstrated additional efficacy in clinical trials and are not recommended due to safety considerations. Adults ≥60 years of age: Maximum dose: 20 mg/day.

Obsessive-compulsive disorder (off-label use): Oral: Adults <60 years of age: Initial: 20 mg once daily; may gradually increase dose based on response and tolerability in 10 to 20 mg increments at intervals ≥1 week up to 40 mg/day. Although doses up to 60 mg/day have been studied, due to safety considerations the recommended maximum dose is 40 mg/day (APA [Koran 2007]; Montgomery 2001). Adults ≥60 years of age: Maximum dose: 20 mg/day. Note: An adequate trial for assessment of effect in obsessive-compulsive disorder is considered to be ≥6 weeks at maximum tolerated dose (Issari 2016).

Panic disorder (off-label use): Oral: Adults <60 years of age: Initial: 10 mg once daily for 3 to 7 days, then 20 mg once daily; may gradually increase dose based on response and tolerability in 10 to 20 mg increments at intervals ≥1 week to 40 mg/day. Although doses up to 60 mg/day have been studied, due to safety considerations the recommended maximum dose is 40 mg/day (APA 2009b; Leinonen 2000; Perna 2001; Seedat 2003; Stahl 2003; Wade 1997). Adults ≥60 years of age: Maximum dose: 20 mg/day.

Posttraumatic stress disorder (off-label use): Oral: Adults <60 years of age: Initial: 20 mg once daily; may gradually increase dose based on response and tolerability in 10 to 20 mg increments 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. (English 2006; Tucker 2003). Adults ≥60 years of age: Maximum dose: 20 mg/day.

Premature ejaculation (off-label use): Oral: Adults <60 years of age: Initial: 20 mg once daily; may gradually increase dose based on response and tolerability at intervals of ≥1 week (some experts suggest 3- to 4-week titration intervals [Khera 2018]) up to a maximum dose of 40 mg/day (Althof 2014; Atmaca 2002a; Safarinejad 2006). Adults ≥60 years of age: Maximum dose: 20 mg/day.

Premenstrual dysphoric disorder (PMDD) (off-label use): Based on limited data:

Continuous daily dosing regimen:Oral: Initial: 10 mg once daily; may gradually increase dose based on response and tolerability (eg, in 10 mg increments) every menstrual cycle up to a maximum dose of 40 mg/day (Casper 2018; Freeman 2002; Wikander 1998).

Intermittent regimens:

Luteal phase dosing regimen: Oral: Initial: 10 mg once daily during the luteal phase of menstrual cycle only (beginning therapy 14 days before anticipated onset of menstruation and continued to the onset of menses); may further increase dose based on response and tolerability (eg, in 10 mg increments) every menstrual cycle up to 30 mg once daily (Casper 2018; Freeman 2002; Wikander 1998).

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; may further increase dose based on response and tolerability (eg, in 10 mg increments) every menstrual cycle up to 30 mg once daily (Casper 2018; Ravindran 2007).

Social anxiety disorder (off-label use): Oral: Adults <60 years of age: Initial: 20 mg once daily; may gradually increase dose based on response and tolerability in 10 to 20 mg increments at intervals ≥1 week up to 40 mg/day. Although doses up to 60 mg/day have been studied, due to safety considerations the recommended maximum dose is 40 mg/day (Atmaca 2002b; Furmark 2005; WFSBP [Bandelow 2012]). Adults ≥60 years of age: Maximum dose: 20 mg/day.

Vasomotor symptoms associated with menopause (alternative agent) (off-label use): Oral: Adults <60 years of age: Initial: 10 mg once daily; may increase dose to 20 mg once daily after 1 week. Doses as high as 40 mg/day have been studied; however, for this indication, doses >20 mg/day have demonstrated little additional benefit and greater adverse effects (Barton 2010; Kalay 2007; NAMS 2015). Adults ≥60 years of age: Maximum dose: 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 antidepressants, gradually taper the dose (eg, over 2 to 4 weeks) to minimize the incidence of withdrawal symptoms and allow for the detection of re-emerging symptoms (APA 2010; WFSBP [Bauer 2015]); antidepressants with a shorter half-life may need to be tapered more slowly (APA 2010) (eg, over 4 weeks [Hirsch 2018a]). If intolerable withdrawal symptoms occur following a dose reduction, resume the previously prescribed dose and/or decrease dose at a more gradual rate (Shelton 2001). Select patients (eg, those with a history of discontinuation syndrome) on long-term treatment (>6 months) may benefit from tapering over >3 months (WFSBP [Bauer 2015]). Evidence supporting ideal taper rates is limited (Shelton 2001; WFSBP [Bauer 2015]).

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 (Hirsch 2018b; Ogle 2013; WFSBP [Bauer 2013]).

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.

Dosing: Geriatric

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. (Blank 2006; Lenze 2005)

Major depressive disorder (unipolar): Adults ≥60 years of age: Oral: Initial: 10 to 20 mg once daily (Marano 2015; VA/DoD 2016); maximum dose in adults ≥60 years of age: 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.

Dosing: Pediatric

Obsessive-compulsive disorder (off-label use): Children and Adolescents: Oral: 10 to 40 mg/day (Mukaddes 2003; Thomsen 1997; Thomsen 2001)

Discontinuation of therapy: Refer to adult dosing.

Switching antidepressants: Refer to adult dosing.

Dosing: Renal Impairment

Mild-to-moderate impairment: No dosage adjustment necessary.

Severe impairment: CrCl <20 mL/minute: No dosage adjustment provided in manufacturer's labeling (has not been studied); use caution.

Dosing: Hepatic Impairment

Initial: 20 mg once daily; maximum recommended dose: 20 mg daily due to decreased clearance and the risk of QT prolongation

Administration

Oral: May be administered without regard to food.

Dietary Considerations

May be taken without regard to food.

Storage

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from moisture.

Drug Interactions

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

Amifampridine: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, both drugs have the potential to decrease the seizure threshold, possibly increasing the risk for seizures. Monitor therapy

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

Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Antipsychotic Agents: Serotonin Modulators may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. 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. Monitor therapy

ARIPiprazole: CYP2D6 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy

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

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

Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Bromopride: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. 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. Consider therapy modification

BusPIRone: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Selective Serotonin Reuptake Inhibitors may decrease the metabolism of BusPIRone. Management: The combination of a selective serotonin reuptake inhibitor and buspirone should be undertaken with great caution. When combined treatment is clinically indicated, monitor closely for signs of serotonin toxicity/serotonin syndrome. Consider therapy modification

CarBAMazepine: May decrease the serum concentration of Citalopram. Monitor therapy

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

Cimetidine: May increase the serum concentration of Citalopram. Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. 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. Monitor therapy

CYP2C19 Inducers (Strong): May increase the metabolism of CYP2C19 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

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 (e.g., serotonin syndrome, QT prolongation, etc.). Consider therapy modification

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

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

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP2C19 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP2C19 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Dapoxetine: May enhance the adverse/toxic effect of Serotonin Modulators. Avoid combination

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

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. Monitor therapy

Desmopressin: Selective Serotonin Reuptake Inhibitors may enhance the adverse/toxic effect of Desmopressin. Monitor therapy

Dextromethorphan: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Dextromethorphan. Selective Serotonin Reuptake Inhibitors may increase the serum concentration of Dextromethorphan. Management: Avoid the concurrent use of dextromethorphan and SSRIs, particularly fluoxetine and paroxetine, when possible. The risk for this interaction may persist for several weeks following discontinuation of fluoxetine or paroxetine. Consider therapy modification

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. Consider therapy modification

Dosulepin: Selective Serotonin Reuptake Inhibitors may increase the serum concentration of Dosulepin. Avoid combination

Doxepin-Containing Products: Citalopram may enhance the QTc-prolonging effect of Doxepin-Containing Products. Citalopram may enhance the serotonergic effect of Doxepin-Containing Products. 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 may be at even higher risk. Monitor therapy

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

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Enzalutamide: May decrease the serum concentration of CYP2C19 Substrates (High risk with Inducers). Conversely, concentrations of active metabolites may be increased for those drugs activated by CYP2C19. Management: Concurrent use of enzalutamide with CYP2C19 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP2C19 substrate should be performed with caution and close monitoring. Consider therapy modification

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

Esomeprazole: May increase the serum concentration of Citalopram. Monitor therapy

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

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. Consider therapy modification

Glucosamine: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Haloperidol: QT-prolonging Antidepressants (Moderate Risk) may enhance the QTc-prolonging effect of Haloperidol. 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. Monitor therapy

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Consider therapy modification

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. Monitor therapy

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

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

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

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

Linezolid: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Consider alternatives to this combination whenever possible. If clinically acceptable, wait at least 2 weeks (5 weeks for fluoxetine) after SSRI discontinuation to initiate linezolid. Consider therapy modification

Linezolid: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Management: Due to a risk of serotonin syndrome/serotonin toxicity, discontinue serotonin modulators 2 weeks prior to the administration of linezolid. If urgent initiation of linezolid is needed, discontinue serotonin modulators immediately and monitor closely. Consider therapy modification

Lithium: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could increase the risk of serotonin toxicity/serotonin syndrome. Management: This combination should be undertaken with great caution. When combined treatment is clinically indicated, monitor closely for signs of serotonin toxicity/serotonin syndrome. Consider therapy modification

Lofexidine: QT-prolonging Antidepressants (Moderate Risk) may enhance the QTc-prolonging effect of Lofexidine. Lofexidine 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. Monitor therapy

Metaxalone: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

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

Methylene Blue: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Avoid combination

Methylphenidate: May enhance the adverse/toxic effect of Serotonin Modulators. Specifically, the risk of serotonin syndrome or serotonin toxicity may be increased. Monitor therapy

Metoclopramide: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Management: Seek alternatives to this combination when possible. Monitor patients receiving metoclopramide with selective serotonin reuptake inhibitors for signs of extrapyramidal symptoms, neuroleptic malignant syndrome, and serotonin syndrome. Consider therapy modification

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

Mexiletine: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of Mexiletine. Consider therapy modification

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Monoamine Oxidase Inhibitors: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. While methylene blue and linezolid are expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Exceptions: Linezolid; Methylene Blue; Tedizolid. Avoid combination

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

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

Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. 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. 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 using alternative analgesics, when appropriate, and/or addition of a gastroprotective agent. Monitor patients closely for signs/symptoms of bleeding, and for evidence of diminished SSRI effectiveness with concurrent use. Consider therapy modification

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

Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. 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. Consider therapy modification

Ondansetron: 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. Monitor therapy

Opioid Analgesics: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. 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. 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. Monitor therapy

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

Perhexiline: CYP2D6 Inhibitors (Weak) may increase the serum concentration of Perhexiline. Monitor therapy

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

Pitolisant: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant. Consider therapy modification

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

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

QT-prolonging Antipsychotics (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. Exceptions: Pimozide. 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. 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. 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. Exceptions: Domperidone; Lofexidine. 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. Exceptions: Fluconazole. 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. 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. Exceptions: Voriconazole. Monitor therapy

RifAMPin: May decrease the serum concentration of Citalopram. Monitor therapy

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. Monitor therapy

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

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Exceptions: Nicergoline; Tedizolid. Monitor therapy

Serotonin Reuptake Inhibitor/Antagonists: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Serotonin Reuptake Inhibitor/Antagonists. This may cause serotonin syndrome. Management: Consider alternatives, and use conservative initial dosing. Monitor patients receiving these combinations for signs/symptoms of serotonin toxicity. Consider therapy modification

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

St John's Wort: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

Tedizolid: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

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

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

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

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

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

TraMADol: Serotonin Modulators may enhance the adverse/toxic effect of TraMADol. The risk of seizures may be increased. TraMADol may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Tricyclic Antidepressants: May enhance the adverse/toxic effect of Citalopram. Tricyclic Antidepressants may increase the serum concentration of Citalopram. Citalopram may increase the serum concentration of Tricyclic Antidepressants. Management: Consider alternatives to this combination when possible. Monitor for adverse effects of tricyclic antidepressants (TCAs), including serotonin syndrome and QT-interval prolongation, when a TCA is being used in combination with citalopram. Exceptions: Doxepin (Systemic); Doxepin (Topical). Consider therapy modification

Tryptophan: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Avoid combination

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

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

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

Adverse Reactions

>10%:

Central nervous system: Drowsiness (18%; dose related), insomnia (15%; dose related)

Dermatologic: Diaphoresis (11%; dose related)

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

1% to 10%:

Cardiovascular: Prolonged Q-T interval on ECG (2%), hypotension (≥1%), orthostatic hypotension (≥1%), tachycardia (≥1%), bradycardia (1%)

Central nervous system: Fatigue (5%; dose related), anxiety (4%), agitation (3%), yawning (2%; dose related), amnesia (≥1%), apathy (≥1%), confusion (≥1%), depression (≥1%), lack of concentration (≥1%), migraine (≥1%), paresthesia (≥1%)

Dermatologic: Skin rash (≥1%), pruritus (≥1%)

Endocrine & metabolic: Decreased libido (1% to 4%), amenorrhea (≥1%), weight gain (≥1%), weight loss (≥1%)

Gastrointestinal: Diarrhea (8%), dyspepsia (5%), anorexia (4%), vomiting (4%), abdominal pain (3%), dysgeusia (≥1%), flatulence (≥1%), increased appetite (≥1%), sialorrhea (≥1%)

Genitourinary: Ejaculatory disorder (6%), dysmenorrhea (3%), impotence (3%; dose related)

Neuromuscular & skeletal: Tremor (8%), arthralgia (2%), myalgia (2%)

Ophthalmic: Accommodation disturbance (≥1%)

Renal: Polyuria (≥1%)

Respiratory: Rhinitis (5%), upper respiratory tract infection (5%), sinusitis (3%), cough (≥1%)

Miscellaneous: Fever (2%)

<1%, postmarketing, and/or case reports: Abnormal gait, abnormal lacrimation, abnormal serum prolactin levels, acne vulgaris, acute renal failure, aggressive behavior, akathisia, alopecia, altered serum glucose, anaphylaxis, anemia, angina pectoris, angioedema, angle-closure glaucoma, arthritis, asthma, ataxia, atrial fibrillation, blepharoptosis, blood coagulation disorder, breast hypertrophy, bronchitis, bronchospasm, bruxism, bundle branch block, bursitis, cardiac arrest, cardiac failure, cataract, catatonia, cellulitis, cerebrovascular accident, cholecystitis, cholelithiasis, choreoathetosis, colitis, conjunctivitis, dehydration, delirium, delusions, depersonalization, dermatitis, diplopia, diverticulitis, drug dependence, dry eye syndrome, duodenal ulcer, dyskinesia, dysphagia, dyspnea, dystonia, dysuria, ecchymoses, eczema, emotional lability, epistaxis, eructation, erythema multiforme, esophagitis, euphoria, extrapyramidal reaction, extrasystoles, eye pain, facial edema, flu-like symptoms, flushing, galactorrhea, gastric ulcer, gastritis, gastroenteritis, gastroesophageal reflux disease, gastrointestinal hemorrhage, gingival hemorrhage, gingivitis, glossitis, goiter, granulocytopenia, gynecomastia, hallucination, hematuria, hemolytic anemia, hemorrhoids, hepatic necrosis, hepatitis, hiccups, hot flash, hyperbilirubinemia, hyperesthesia, hyperkinesia, hypersensitivity reaction, hypertension, hypertonia, hypertrichosis, hypochromic anemia, hypoesthesia, hypoglycemia, hypohidrosis, hypokalemia, hypokinesia, hyponatremia, hypoprothrombinemia, hypothyroidism, increased libido, increased liver enzymes, increased serum alkaline phosphatase, increased thirst, involuntary muscle movements, ischemic heart disease, jaundice, keratitis, laryngitis, leg cramps, leukocytosis, leukopenia, lymphadenopathy, lymphocytopenia, lymphocytosis, mastalgia, melanosis, myasthenia, mydriasis, myocardial infarction, myoclonus, nephrolithiasis, neuralgia, neuroleptic malignant syndrome (Stevens 2008), nightmares, nystagmus, obesity, oliguria, osteoporosis, pancreatitis, panic attack, paranoia, peripheral edema, phlebitis, photophobia, pneumonia, pneumonitis, priapism, pruritus ani, psoriasis, psychosis, pulmonary embolism, purpura, pyelonephritis, Raynaud's phenomenon (Khouri 2016; Peiró 2007), renal pain, rhabdomyolysis, rigors, seasonal allergic rhinitis, seizure, serotonin syndrome, skeletal pain, skin discoloration, skin photosensitivity, stomatitis, stupor, syncope, thrombocytopenia, thrombosis, tinnitus, tonic-clonic seizures, torsades de pointes, toxic epidermal necrolysis, transient ischemic attacks, urinary incontinence, urinary retention, urticaria, vaginal hemorrhage, ventricular arrhythmia, vertigo, withdrawal syndrome, xeroderma

ALERT: U.S. Boxed Warning

Suicidality and antidepressants:

Antidepressants increased the risk of suicidal thinking and behavior (suicidality) compared with placebo in short-term studies in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders. Anyone considering the use of citalopram or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared with placebo in adults older than 24 years; there was a reduction in risk with antidepressants compared with placebo in adults 65 years and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Appropriately monitor and closely observe patients of all ages who are started on antidepressant therapy for clinical worsening, suicidality, or unusual changes in behavior. Advise families and caregivers of the need for close observation and communication with the health care provider. Citalopram is not approved for use in pediatric patients.

Warnings/Precautions

Major psychiatric warnings:

• Suicidal thinking/behavior: [US Boxed Warning]: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18 to 24 years of age) with major depressive disorder (MDD) and other psychiatric disorders; consider risk prior to prescribing. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ≥65 years. Closely monitor patients for clinical worsening, suicidality, or unusual changes in behavior, particularly during the initial 1 to 2 months of therapy or during periods of dosage adjustments (increases or decreases); the patient's family or caregiver should be instructed to closely observe the patient and communicate condition with health care provider. A medication guide concerning the use of antidepressants should be dispensed with each prescription. Citalopram is not FDA approved for use in children.

- The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Patients treated with antidepressants should be observed for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Use caution in high-risk patients during initiation of therapy.

- Prescriptions should be written for the smallest quantity consistent with good patient care. The patient's family or caregiver should be alerted to monitor patients for the emergence of suicidality and associated behaviors such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania; patients should be instructed to notify their healthcare provider if any of these symptoms or worsening depression or psychosis occur.

Concerns related to adverse effects:

• Bleeding risk: May impair platelet aggregation resulting in increased risk of bleeding events, particularly if used concomitantly with aspirin, NSAIDs, warfarin, or other anticoagulants. Bleeding (including GI bleeding) related to SSRI or SNRI use has been reported to range from relatively minor bruising and epistaxis to life-threatening hemorrhage.

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

• Fractures: Bone fractures have been associated with antidepressant treatment. Consider the possibility of a fragility fracture if an antidepressant-treated patient presents with unexplained bone pain, point tenderness, swelling, or bruising (Rabenda 2013; Rizzoli 2012).

• Ocular effects: May cause mild pupillary dilation which in susceptible individuals can lead to an episode of narrow-angle glaucoma. Consider evaluating patients who have not had an iridectomy for narrow-angle glaucoma risk factors.

• QT prolongation: Causes dose-dependent QTc prolongation; torsade de pointes, ventricular tachycardia, and sudden death have been reported. Due to this risk, doses >40 mg/day are not recommended. Additionally, the maximum daily dose should not exceed 20 mg/day in certain populations (eg, CYP2C19 poor metabolizers, patients with hepatic impairment, elderly patients). Use is not recommended in patients with congenital long QT syndrome, bradycardia, recent MI, uncompensated heart failure, hypokalemia, and/or hypomagnesemia, or patients receiving concomitant medications which prolong the QT interval; if use is essential and cannot be avoided in these patients, ECG monitoring is recommended. Discontinue therapy in any patient with persistent QTc measurements >500 msec. Serum electrolytes, particularly potassium and magnesium, should be monitored prior to initiation and periodically during therapy in any patient at increased risk for significant electrolyte disturbances; hypokalemia and/or hypomagnesemia should be corrected prior to use.

• Serotonin syndrome: Potentially life-threatening serotonin syndrome (SS) has occurred with serotonergic agents (eg, SSRIs, SNRIs), particularly when used in combination with other serotonergic agents (eg, triptans, TCAs, fentanyl, lithium, tramadol, buspirone, St John's wort, tryptophan) or agents that impair metabolism of serotonin (eg, MAO inhibitors intended to treat psychiatric disorders, other MAO inhibitors [ie, linezolid and intravenous methylene blue]). Monitor patients closely for signs of SS such as mental status changes (eg, agitation, hallucinations, delirium, coma); autonomic instability (eg, tachycardia, labile blood pressure, diaphoresis); neuromuscular changes (eg, tremor, rigidity, myoclonus); GI symptoms (eg, nausea, vomiting, diarrhea); and/or seizures. Discontinue treatment (and any concomitant serotonergic agent) immediately if signs/symptoms arise.

• Sexual dysfunction: May cause or exacerbate sexual dysfunction.

• SIADH and hyponatremia: SSRIs and SNRIs have been associated with the development of SIADH; hyponatremia has been reported rarely (including severe cases with serum sodium <110 mmol/L), predominately in the elderly; reversible with discontinuation of treatment. Volume depletion and/or concurrent use of diuretics likely increases risk.

Disease-related concerns:

• Heart failure: In a scientific statement from the American Heart Association, citalopram has been determined to be an agent that may exacerbate underlying myocardial dysfunction (magnitude: major) (AHA [Page 2016]).

• Hepatic impairment: Use with caution in patients with hepatic impairment; clearance is decreased and plasma concentrations are increased; a maximum of 20 mg/day is recommended in any patient with hepatic impairment due to the risk of QT prolongation.

• Mania/hypomania: May worsen psychosis in some patients or precipitate a shift to mania or hypomania in patients with bipolar disorder. Monotherapy in patients with bipolar disorder should be avoided. Patients presenting with depressive symptoms should be screened for bipolar disorder. Citalopram is not FDA approved for the treatment of bipolar depression.

• Renal impairment: Use with caution in patients with severe renal impairment (pharmacokinetic information is not available). Clearance is decreased in patients with mild to moderate renal impairment, although no dosage adjustment is necessary.

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

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

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.

• Elderly: Pharmacokinetics are altered in patients ≥60 years of age; a lower maximum dose of 20 mg/day is recommended in this population because of the risk of QT prolongation.

• 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.

• Pregnancy: Use caution in pregnant patients; high doses of citalopram have been associated with teratogenicity in animals.

Other warnings/precautions:

• Discontinuation syndrome: Abrupt discontinuation or interruption of antidepressant therapy has been associated with a discontinuation syndrome. Symptoms arising may vary with antidepressant however commonly include nausea, vomiting, diarrhea, headaches, light-headedness, dizziness, diminished appetite, sweating, chills, tremors, paresthesias, fatigue, somnolence, and sleep disturbances (eg, vivid dreams, insomnia). Less common symptoms include electric shock-like sensations, cardiac arrhythmias (more common with tricyclic antidepressants), myalgias, parkinsonism, arthralgias, and balance difficulties. Psychological symptoms may also emerge such as agitation, anxiety, akathisia, panic attacks, irritability, aggressiveness, worsening of mood, dysphoria, mood lability, hyperactivity, mania/hypomania, depersonalization, decreased concentration, slowed thinking, confusion, and memory or concentration difficulties. Greater risks for developing a discontinuation syndrome have been associated with antidepressants with shorter half-lives, longer durations of treatment, and abrupt discontinuation.. For antidepressants of short or intermediate half-lives, symptoms may emerge within 2 to 5 days after treatment discontinuation and last 7 to 14 days (APA 2010; Fava 2006; Haddad 2001; Shelton 2001; Warner 2006).

• Electroconvulsive therapy (ECT): Use with caution; no clinical studies have assessed the combined use of citalopram and ECT; may increase the risks (eg, cognitive adverse effects) associated with ECT; consider discontinuing, when possible, prior to ECT treatment.

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]); signs/symptoms of arrhythmias (eg, dizziness, palpitations, syncope); liver function tests and CBC with continued therapy; monitor patient periodically for symptom resolution; signs/symptoms of serotonin syndrome; mental status for depression, suicidal ideation (especially at the beginning of therapy or when doses are increased or decreased), anxiety, social functioning, mania, panic attacks; akathisia

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies. Citalopram and its metabolites cross the human placenta (Heikkinen, Ekblad, Kero 2002). An increased risk of teratogenic effects, including cardiovascular defects, may be associated with maternal use of citalopram or other SSRIs; however, available information is conflicting. Nonteratogenic effects in the newborn following SSRI/SNRI exposure late in the third trimester include respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypo- or hypertonia, hyper-reflexia, jitteriness, irritability, constant crying, and tremor. Symptoms may be due to the toxicity of the SSRIs/SNRIs or a discontinuation syndrome and may be consistent with serotonin syndrome associated with SSRI treatment. Persistent pulmonary hypertension of the newborn (PPHN) has also been reported with SSRI exposure. The long-term effects of in utero SSRI exposure on infant development and behavior are not known.

Due to pregnancy-induced physiologic changes, women who are pregnant may require adjusted doses of citalopram to achieve euthymia (Heikkinen, Ekblad, Kero 2002). The ACOG recommends that therapy with SSRIs or SNRIs during pregnancy be individualized; treatment of depression during pregnancy should incorporate the clinical expertise of the mental health clinician, obstetrician, primary health care provider, and pediatrician. According to the American Psychiatric Association (APA), the risks of medication treatment should be weighed against other treatment options and untreated depression. For women who discontinue antidepressant medications during pregnancy and who may be at high risk for postpartum depression, the medications can be restarted following delivery. Treatment algorithms have been developed by the ACOG and the APA for the management of depression in women prior to conception and during pregnancy (ACOG 2008; APA 2010; Yonkers 2009).

Pregnant women exposed to antidepressants during pregnancy are encouraged to enroll in the National Pregnancy Registry for Antidepressants (NPRAD). Women 18 to 45 years of age or their health care providers may contact the registry by calling 844-405-6185. Enrollment should be done as early in pregnancy as possible.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea, fatigue, dry mouth, lack of appetite, loss of strength and energy, insomnia, tremors, diarrhea, sweating a lot, or yawning. Have patient report immediately to prescriber signs of low sodium (headache, difficulty focusing, memory impairment, confusion, weakness, seizures, or change in balance), signs of depression (suicidal ideation, anxiety, emotional instability, or confusion), signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding), agitation, panic attacks, mood changes, angina, tachycardia, abnormal heartbeat, shortness of breath, dizziness, passing out, seizures, sexual dysfunction, weight gain, weight loss, menstrual changes, vision changes, eye pain, eye irritation, signs of serotonin syndrome (dizziness, severe headache, agitation, hallucinations, tachycardia, abnormal heartbeat, flushing, tremors, sweating a lot, change in balance, severe nausea, or severe diarrhea), or priapism (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Hide