Citalopram

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[edit] BRAND NAMES

[edit] STRUCTURE

Citalopram.jpg

Citalopram is a racemic mixture (50/50). The (S)-enantiomer (Escitalopram) is responsible of the antidepressant effect.

[edit] MECHANISM OF ACTION

Citalopram is a selective serotonin reuptake inhibitor (SSRI). It blocks the reuptake of serotonin into the presynaptic cell, increasing its level within the synaptic cleft. SSRIs bind with significantly less affinity to histamine, acetylcholine, and norepinephrine receptors than tricyclic antidepressant drugs

CYP3A4 and CYP2C19 are the primary enzymes involved in the metabolism of citalopram

[edit] INDICATIONS

  • Treatment of Major depressive disorder : A major depressive episode implies a prominent and relatively persistent depressed or dysphoric mood that usually interferes with daily functioning (nearly every day for at least 2 weeks; it should include at least 4 of the following 8 symptoms: change in appetite, change in sleep, psychomotor agitation or retardation, loss of interest in usual activities or decrease in sexual drive, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, and a suicide attempt or suicidal ideation
  • Treatment of Panic disorder (panic attacks). Citalopram is licensed for this indication in the UK and other European countries
  • Treatment of Obsessive-Compulsive disorder (OCD).[1]

[edit] DOSAGE

Adult Dose:

  • Depression: initial dose should be 20mg/day, in the morning or evening, with or without food. Dosage may be increased up to max 40mg/day. The maximum dose should also be limited to 20 mg/day in patients with hepatic impairment and in patients who are greater than 60 years of age because of expected higher exposures. Patients may notice improvement with Citalopram therapy in 1 to 4 weeks, they also should be advised to continue therapy as directed.
  • Panic disorder: The starting dose is 10 mg per day for the first week before increasing the dose to 20.30 mg per day. Dosage may be increased up to max 40mg/day.
  • Obsessive-Compulsive disorder: The starting dose is 20 mg per day. Dosage may be increased up to max 40mg/day.

[edit] CONTRAINDICATIONS

  • Hypersensitivity to Citalopram
  • It's use within 14 days of stopping an MAOI because of an increased risk of Serotonin syndrome
  • Concomitant use with Pimozide (Orap®) because this can cause serious heart problems (QT prolongation)

[edit] WARNINGS AND PRECAUTIONS

  • FDA Black Box Warning for Citalopram : Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) 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 to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Citalopram is not approved for use in pediatric patients.


  • Abnormal heart rhythm (QTc interval prolongation): Recently (March 2012), both the manufacturer of citalopram and the US Food and Drug Administration have warned health care providers and patients about new information implicating drug-induced QTc interval prolongation and torsade de pointes when using citalopram in doses >40 mg/day. It is recommended that citalopram should not be given at doses above 40 mg/day.
    Citalopram should be discontinued in patients who are found to have persistent QTc measurements >500 ms. If patients taking citalopram experience symptoms that could indicate the occurrence of cardiac arrhythmias, e.g., dizziness, palpitations, or syncope, the prescriber should initiate further evaluation, including cardiac monitoring.


  • Serotonin Syndrome: Serotonin syndrome has been reported with SSRIs and SNRIs, including Citalopram , both when taken alone, but especially when co-administered with other serotonergic agents (including Triptans, Tricyclic antidepressants, Fentanyl, Lithium, Tramadol, Tryptophan, Buspirone and St. John’s Wort). Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).If such symptoms occur, discontinue Citalopram and initiate supportive treatment. If concomitant use of Citalopram with other serotonergic drugs is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases.
  • Abnormal Bleeding: May increase the risk of bleeding. Use with NSAIDs, aspirin, warfarin, or drugs that affect coagulation may potentiate the risk of gastrointestinal or other bleeding
  • Hyponatremia: Hyponatremia has been reported with Citalopram use, either alone or in combination with some diuretics (Hydrochlorothiazide, Furosemide). Hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Signs and symptoms include headache, new or increased seizure frequency, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which can lead to fall. Severe Hyponatremia may cause hallucination, syncope, seizure, coma, respiratory arrest, and death.

[edit] INTERACTIONS

[edit] PREGNANCY AND LACTATION

  • Pregnancy Category C (US). There are no adequate and well-controlled studies in pregnant women, that's why, Citalopram should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
  • Citalopram is excreted in human breast milk. The decision whether to continue or discontinue either nursing or Citalopram therapy should take into account the risks of exposure for the infant and the benefits of treatment for the mother.

[edit] SIDE EFFECTS

Possible side effects include: Dry mouth, tremor, insomia, somnolence, nausea, diarrhea, abdominal pain, fatigue, agitation, anorexia, sexual dysfunction (Decreased libido, ejaculation disorder and impotence).

For more serious adverse effects (see WARNINGS AND PRECAUTIONS)

[edit] RELATED LINKS

[edit] BIBLIOGRAPHY

[edit] REFERENCES

  1. http://www.ncbi.nlm.nih.gov/pubmed/9395151
Antidepressants
Tricyclic antidepressants Amitriptyline (Elavil, Laroxyl)   Clomipramine (Anafranil)   Doxepin (Sinequan)   Imipramine (Tofranil)   Nortriptyline (Aventyl, Pamelor)   Trimipramine (Surmontil)
Selective serotonin reuptake inhibitors (SSRIs) Citalopram (Celexa, Seropram)   Escitalopram (Cipralex, Lexapro)   Fluoxetine (Prozac)   Fluvoxamine (Luvox, Maveral)   Paroxetine (Paxil, Seroxat)   Sertraline (Zoloft)
Serotonin–norepinephrine reuptake inhibitors (SNRIs) Desvenlafaxine (Pristiq)   Duloxetine (Cymbalta, Xeristar)   Venlafaxine (Efexor, Effexor)
Serotonin antagonists and reuptake inhibitors (SARIs) Trazodone (Desyrel, Oleptro)
Norepinephrine reuptake inhibitors (NRIs) Maprotiline (Ludiomil)   Reboxetine (Edronax)
Norepinephrine-dopamine reuptake inhibitors (NDRIs) Bupropion (Wellbutrin)
Noradrenergic and specific serotonergic antidepressants (NaSSAs) Mianserin (Lantanon)   Mirtazapine (Remeron)
Norepinephrine-dopamine disinhibitors (NDDIs) Agomelatine (Valdoxan, Thymanax)
Monoamine oxidase inhibitors Nonselective Tranylcypromine (Parnate)
Monoamine oxidase inhibitors B-Selective Selegiline (Transdermal) (Emsam)
Others 5-Hydroxytryptophan   S-Adenosyl methionine   Hypericum (St John's wort)