Citalopram


Article Author:
Nazila Sharbaf Shoar


Article Editor:
Ranjit Padhy


Editors In Chief:
Casey Ciresi


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James Hughes
Beenish Sohail
Hajira Basit
Phillip Hynes
Sandeep Sekhon


Updated:
10/1/2019 12:57:51 PM

Indications

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:

  • Alcoholism
  • 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.

Administration

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 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. 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 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 patient 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.

Contraindications

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 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.

Monitoring

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. 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) are 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

Toxicity is not expected by 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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Citalopram - Questions

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Citalopram is indicated for the treatment of which of the following disorders?



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Which of the following medications can be used to treat depression?



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What is the brand name for citalopram?



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Citalopram falls into which of the following drug classifications?



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A 30-year-old female is being evaluated at her primary care physician's office for insomnia, loss of pleasure, and poor concentration. Past medical history includes anorexia nervosa. She has been in remission for one year and regularly follows with a nutritionist and psychologist for dietary and cognitive behavioral therapies, respectively. The patient takes a multivitamin, denies alcohol or illicit drug use, and is not sexually active. Vital signs are stable, and the body mass index is 21 kg/m2. Physical examination reveals a well-developed female in no acute distress without lid lag or resting tremor. Cardiac auscultation reveals a regular rate without murmurs. Neurologic exam is negative for focal deficits. Urine beta-hCG is negative, hemoglobin is 12.9 mg/dL (12-16 mg/dL), and TSH is 2.5 IU/L (0.5-5.0 IU/L). Electrocardiogram demonstrates normal sinus rhythm with a QT interval of 430 msec. In addition to continuing cognitive behavioral therapy, which of the following is the most appropriate next step in management?



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A novice nurse is caring for a client with a generalized anxiety disorder. A prescription for citalopram 20 mg given orally now, then daily, has been placed by the healthcare provider on morning rounds is the nurse's priority at this moment. While at the automated dispensing unit, the clinical instructor approaches with a big smile on her face. The student nurse recognizes that she is about to be quizzed on the medication in her hand before delivery. Unintimidated after a night of intense studying for this very moment, the nurse proceeds to list all the adverse effects she can recall. What adverse effects or adverse events listed exhibit the novice nurse has indeed mastered the content? Select all that apply.



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Citalopram - References

References

Lochmann D,Richardson T, Selective Serotonin Reuptake Inhibitors. Handbook of experimental pharmacology. 2019 Mar 6;     [PubMed]
Luo Y,Chaimani A,Kataoka Y,Ostinelli EG,Ogawa Y,Cipriani A,Salanti G,Furukawa TA, Evidence synthesis, practice guidelines and real-world prescriptions of new generation antidepressants in the treatment of depression: a protocol for cumulative network meta-analyses and meta-epidemiological study. BMJ open. 2018 Dec 9;     [PubMed]
Wagner E,Löhrs L,Siskind D,Honer WG,Falkai P,Hasan A, Clozapine augmentation strategies - a systematic meta-review of available evidence. Treatment options for clozapine resistance. Journal of psychopharmacology (Oxford, England). 2019 Jan 30;     [PubMed]
Escitalopram 2006;     [PubMed]
Alušík Š,Paluch Z, [Citalopram and QT prolongation]. Vnitrni lekarstvi. Winter 2018;     [PubMed]
Hekmatjah J,Tareen K,Tareen RS, Citalopram-Associated Alopecia: A Case Report and Brief Literature Review. Current drug safety. 2019 Feb 14;     [PubMed]
Aboukarr A,Giudice M, Interaction between Monoamine Oxidase B Inhibitors and Selective Serotonin Reuptake Inhibitors. The Canadian journal of hospital pharmacy. 2018 May-Jun;     [PubMed]
Rahikainen AL,Vauhkonen P,Pett H,Palo JU,Haukka J,Ojanperä I,Niemi M,Sajantila A, Completed suicides of citalopram users-the role of CYP genotypes and adverse drug interactions. International journal of legal medicine. 2019 Mar;     [PubMed]
Macaluso M,Preskorn SH, Knowledge of the Pharmacology of Antidepressants and Antipsychotics Yields Results Comparable With Pharmacogenetic Testing. Journal of psychiatric practice. 2018 Nov;     [PubMed]

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