Article Author:
Nazila Sharbaf Shoar
Article Author:
Kamron Fariba
Article Editor:
Ranjit Padhy
3/30/2020 2:17:01 PM
PubMed Link:


Citalopram hydrobromide is a selective serotonin reuptake inhibitor. [1]The primary FDA-approved clinical use for citalopram hydrobromide is for the treatment of depression in adults:

  • Recommendation: Adult, class IIa
  • Strength of Evidence: Adult, category B

Non-FDA-approved uses include:

  • Alcohol use disorder
  • Coronary arteriosclerosis
  • Obsessive-compulsive disorder
  • Panic disorder
  • Postmenopausal flushing
  • Premenstrual dysphoric disorder

FDA has not approved citalopram hydrobromide for the above uses. Advantages and disadvantages of using this drug in the non-FDA approved conditions are based on the patient's condition and physician’s judgment.

Mechanism of Action

Citalopram hydrobromide acts as an antidepressant by potentiating the serotonergic activity in the central nervous system (CNS). Multiple studies in the past confirmed that citalopram hydrobromide is a selective serotonin reuptake inhibitor (SSRI) and that it does not have any effect on norepinephrine or dopamine reuptake.[2] It has a low affinity for muscarinic acetylcholine receptors, but no significant effect on alpha- or beta-adrenergic receptors or dopamine-1, dopamine-2, histamine, 5HT1A, 5HT1B, gamma-aminobutyric acid, opioid, or benzodiazepine receptors.

  • The onset of action for depression is about 1 to 4 weeks. However, the full response may take 8 to 12 weeks after initiation of treatment.
  • Bioavailability is 80%: Tablets and oral solution are bioequivalent
  • Half-life is 24 to 48 hours (average: 35 hours); however, half-life significantly increases in patients with hepatic impairment, mild-to-moderate renal impairment, in elderly patients (60 years or older), and in poor CYP2C19 metabolizers.


The oral route for adults younger than 60 years:

  • Initial dose of 20 mg once daily (morning or evening, with or without food)
  • Increase the dose to 40 mg after one week (maximum dose of 40 mg daily)
  • Maximum dose of 20 mg daily should be given to patients older than 60 years old or poor metabolizers of CYP2C19 20

Additional efficacy with doses of more than 40 mg daily has not been demonstrated in clinical trials.

Doses more than 40 mg daily are not recommended due to the risk of QT prolongation.[3][4][5]

Adverse Effects

 Common adverse effects are greater than 10%:[6][7]

  • CNS: Drowsiness, insomnia, dizziness, headache
  • Dermatologic: Diaphoresis
  • Gastrointestinal (GI): Nausea, vomiting, xerostomia, constipation, diarrhea

Less common serious adverse effects:

  • Cardiovascular: Myocardial infarction, prolonged QT interval, Torsades de pointes
  • Hematologic: Hemorrhage, abnormal
  • Neurologic: Cerebrovascular accident
  • Psychiatric: Suicidal thoughts, suicide
  • Other: Serotonin syndrome

A rare adverse effect is hyponatremia. Citalopram has been shown to produce hypernatremia in case reports involving elderly patients. In addition to advanced age, other factors such as female gender, concurrent diuretic use, low body weight, and recent pneumonia may increase the likelihood of hypernatremia.

Black Box Warning

Citalopram hydrobromide has been associated with suicidality and worsening depression especially in children, adolescents, and young adults (younger than 24 years old). Antidepressants increased the risk of suicidal thinking compared to placebo in children, adolescents, and young adults. The advantages and disadvantages of using citalopram hydrobromide or any other antidepressant in these populations are based on the patient's condition and physician’s judgment.[8]

Patients of any age who start antidepressant therapy should be monitored and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Citalopram hydrobromide is not approved for use in pediatric patients.

Increased risk of suicidal ideation and treatment-emergent suicidal ideation (TESI) has been a real concern in younger patients at the onset of therapy. However recent studies showed the lowest rate of suicide in the group of patients receiving citalopram compared to the groups receiving a placebo. In the case of citalopram, analysis of the date from 17 controlled clinical trials involving 5000 patients indicated that the group of patients receiving citalopram had the lowest rate of suicide compared with the group receiving placebo, a tricyclic antidepressant, or other SSRI. A meta-analysis of the escitalopram clinical trial database-consisting of 2277 escitalopram-treated patients and 1814 placebo-treated patients- also yield no indication the escitalopram increase suicidal behavior in major depressive disorder and anxiety disorder.

Family and twin studies provide some evidence of a genetic influence on suicidal behavior, and it has been postulated that TESI may also be genetically influenced.


Citalopram is contraindicated in patients with a history of hypersensitivity to the drug or components. It is also contraindicated with monoamine oxidase inhibitors, including linezolid or IV methylene blue and also pimozide.

Do not start citalopram within 14 days of discontinuing an MAOI due to an increased risk of serotonin syndrome.

Canadian labeling includes additional contraindications not included on United States labeling: known QT interval prolongation or congenital long QT syndrome.


Prior to initiation of the treatment:

Monitor and evaluate the electrolytes especially potassium and magnesium prior to initiation of therapy. Reevaluating electrolyte in patients at risk for electrolyte disturbances during the treatment is recommended.  

Monitor patients for QT-prolongation.  ECG in patients with congenital long QT syndrome, bradycardia, hypokalemia or hypomagnesemia, recent acute myocardial infarction, uncompensated heart failure, or concomitant use of other QT-prolonging drugs should be done.  

During the treatment:

Patients need to be assessed and monitored for worsening of depression, suicidality, or unusual changes in behavior during the initial few months of therapy or when the dose increases or decreases. Weekly face-to-face contact with patients during the initial one month of treatment, then visits every other week for the next month, then at three months, and then as clinically indicated is highly recommended.

Weight and growth should be monitored regularly by a physician during treatment in children and adolescents.

Abrupt discontinuation of antidepressant (Also known as discontinuation syndrome):

Discontinuation syndrome is commonly seen in patients who suddenly stop antidepressant therapy. The most common symptoms include nausea, vomiting, diarrhea, headaches, light-headedness, dizziness, diminished appetite, sweating, chills, tremors, fatigue, somnolence, and sleep disturbances.  Less common symptoms include electric shock-like sensations, cardiac arrhythmias, myalgia, arthralgia, and balance difficulties. Due to these side effects, gradual tapering of the antidepressant over several weeks to several months (based on the treatment duration) is highly recommended. The half-life of drugs and duration of the therapy should be considered as antidepressants with a shorter half-life may need to be tapered more conservatively.


Toxicity is not expected by the ingestion of up to 100 mg citalopram hydrobromide. However, there is a chance of developing serotonin toxicity even at therapeutic doses, especially if another medication that increases CNS serotonin is used concomitantly.

Ingestion of more than 600 mg citalopram requires 8 hours, and ingestion of more than 1000 mg citalopram requires 13 hours of cardiac monitoring. At the end of the observation period, if the patient is asymptomatic and QTc is less than 450 milliseconds, the patient can be discharged. However, in patients with QTc of greater than 450 milliseconds at the end of the observation period inpatient continued cardiac monitoring is necessary.[9]

Enhancing Healthcare Team Outcomes

Citalopram hydrobromide is a widely prescribed antidepressant by the nurse practitioner, primary care provider, psychiatrist, internist and the neurologist. While the drug is effective for depression, its use must be monitored. The drug has been associated with suicidality and worsening depression especially in children, adolescents, and young adults (younger than 24 years old).  In addition, one should monitor electrolytes and obtain an ECG prior to starting treatment because of the risk of prolonged QT syndrome. Patients should be educated not to combine the drug with alcohol, sedatives and other antidepressants. 


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