Citalopram, Celexa®

• Celexa®

• Selective Serotonin Reuptake Inhibitor (SSRI)
• Antidepressant

• Solution, oral: 10 mg/5 mL (240 mL)
• Tablet, oral: 10 mg, 20 mg, 40 mg

• Treatment of major depression
• Treatment of obsessive compulsive disorders

• Onset of action: Depression: The onset of action is within a week; however, individual response varies greatly and full response may not be seen until 8-12 weeks after initiation of treatment.
• Bioavailability: 80%
• Half-life elimination: 24-48 hours (average: 35 hours); doubled with hepatic impairment
• Time to peak, serum: 1-6 hours, average within 4 hours
• Excretion: Urine

• Metabolism: Extensively hepatic, via CYP3A4 and 2C19 (major pathways), and 2D6 (minor pathway); forms metabolites, N-demethylcitalopram (DCT) and didemethylcitalopram (DDCT) which are at least eight times less potent than citalopram

Adult dosing:

• Initial: 20 mg/day
• Maximum dose in adults <60 years: 40 mg/day
• Maximum dose in adults ≥60 years: 20 mg/day

Dosing: Pediatric

• Obsessive-compulsive disorder (open-label): 10-40 mg/day

Dosing adjustment:

• Mild-to-moderate renal impairment: No dosage adjustment needed.
• Severe impairment: Cl_cr <20 mL/minute: Use with caution.

Dosing: Hepatic Impairment

• Maximum dose: 20 mg/day due to increased serum concentrations and the risk of QT prolongation

• Alcohol (Ethyl) may enhance the adverse/toxic effect of SSRIs
• SSRIs may decrease the metabolism of Alpha-/Beta-Blockers.
• Opioids may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome.
• SSRIs may enhance the antiplatelet effect of Aspirin.
• When used with other SSRIs may cause serotonin syndrome
• SSRIs may decrease the metabolism of Carbamazepine
• Cimetidine may decrease the metabolism of SSRIs
• Ciprofloxacin may enhance the QTc-prolonging effect of QTc-Prolonging Agents
• SSRIs may decrease the metabolism of Clozapine
• Cyproheptadine may diminish the therapeutic effect of SSRIs
• SSRIs may enhance the adverse/toxic effect of Desmopressin.
• SSRIs may enhance the serotonergic effect of Dextromethorphan
• Fluconazole may increase the serum concentration of Citalopram
• SSRIs may decrease the metabolism of Haloperidol.
• SSRIs may enhance the adverse/toxic effect of Lithium.
• Macrolide Antibiotics may decrease the metabolism of SSRIs
• MAO Inhibitors may enhance the serotonergic effect of SSRIs
• SSRIs may decrease the metabolism of Methadone. Fluvoxamine appears to be the only interacting SSRI.
• Metoclopramide may enhance the adverse/toxic effect of SSRIs
• Quetiapine may enhance the QTc-prolonging effect of QTc-Prolonging Agents
• SSRIs may decrease the metabolism of Risperidone.
• SSRIs may decrease the metabolism of Tricyclic Antidepressants.
• Tryptophan may enhance the serotonergic effect of SSRIs. This may cause serotonin syndrome.
• SSRIs may enhance the anticoagulant effect of Vitamin K Antagonists.

• Somnolence (18%; dose related)
• insomnia (15%; dose related)
• Gastrointestinal: Nausea (21%)
• xerostomia (20%)
• Diaphoresis (11%; dose related)
• Fatigue (5%; dose related)
• Anorexia (4%)
• Anxiety (4%)
• Agitation (3%)
• Fever (2%)
• yawning (2%; dose related)
• Rash, pruritus
• Libido decreased (1% to 4%)
• Dysmenorrhea (3%), amenorrhea, sexual dysfunction
• Diarrhea (8%)
• Dyspepsia (5%)
• Vomiting (4%)
• Abdominal pain (3%)
• flatulence, salivation increased, taste perversion, weight gain/loss
• Ejaculation disorder (6%)
• impotence (3%; dose related), polyuria
• Tremor (8%),
• Arthralgia (2%)
• Myalgia (2%)
• Ocular: Abnormal accommodation
• Rhinitis (5%),
• Upper respiratory tract infection (5%),
• sinusitis (3%), cough
• Bleeding risk: May increase risk of bleeding particularly if used concomitantly with aspirin, NSAIDs, warfarin, or other anticoagulants.
• CNS depression
• QT prolongation (ECG monitoring is recommended. Avoid doses >40 mg/day)
• Serotonin syndrome (SS)/neuroleptic malignant syndrome (NMS)-like reactions
• Sexual dysfunction
• SIADH and hyponatremia
• Mania/hypomania
• Use with caution in patients with a previous seizure disorder or condition predisposing to seizures such as brain damage or alcoholism

• Hypersensitivity to citalopram or any component of the formulation
• Concomitant use with MAO inhibitors or within 2 weeks of discontinuing MAO inhibitors;
• Concomitant use with pimozide
• Patients with congenital long QT syndrome

• Category C
• Due to adverse effects observed in animal studies, citalopram is classified as pregnancy category C.
• Citalopram and its metabolites cross the human placenta.
• Nonteratogenic effects in the newborn following SSRI 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
  • tremor
  • low birth weight and
  • lower Apgar scores
  • Exposure to SSRIs after the twentieth week of gestation has been associated with persistent pulmonary hypertension of the newborn (PPHN)

Breast-Feeding Considerations

• Citalopram and its metabolites are excreted in human milk. the decision to continue or discontinue breast-feeding during therapy should take into account the risk of exposure to the infant and the benefits of treatment to the mother.
• Excessive somnolence, decreased feeding, colic, irritability, restlessness, and weight loss have been reported in breast-fed infants.
• The long-term effects on development and behavior have not been studied; therefore, citalopram should be prescribed to a mother who is breast-feeding only when the benefits outweigh the potential risks.

Monitoring Parameters

• ECG
• liver function tests
• CBC with continued therapy
• 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
• Teach patient hypotensive precautions

• Suicidal thinking/behavior: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18-24 years of age) with major depressive disorder (MDD) and other psychiatric disorders
• Citalopram is not FDA approved for use in children.
• 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.

• Boyer EW and Shannon M, “The Serotonin Syndrome,” N Engl J Med, 2005, 352:1112-20.
• Dunkley EJ, Isbister GK, Sibbritt D, et al, “The Hunter Serotonin Toxicity Criteria: Simple and Accurate Diagnostic Decision Rules for Serotonin Toxicity,” QJM, 2003, 96(9):635-42.
• Mahlberg R, Kunz D, Sasse J, et al, “Serotonin Syndrome With Tramadol and Citalopram,” Am J Psychiatry, 2004, 161(6):1129.
• Mokhlesi B, Leikin JB, Murray P, et al, “Adult Toxicology in Critical Care: Part II: Specific Poisonings,” Chest, 2003, 123(3):897-922.
• Pass SE and Simpson RW, “Discontinuation and Reinstitution of Medications During the Perioperative Period,” Am J Health Syst Pharm, 2004, 61(9):899-912.