CIPRALEX 10 MG

Indications

• Depressive illness
• Generalized anxiety disorder
• Obsessive-compulsive disorder
• Panic disorder
• Social anxiety disorder

Mechanism of action

Escitalopram enhances serotonergic activity by binding to the primary binding site on the serotonin transporter (SERT), preventing the re-uptake of serotonin into the presynaptic neuron. It also acts as an allosteric serotonin re-uptake inhibitor, binding to a secondary allosteric site on SERT to more effectively inhibit serotonin re-uptake, leading to elevated extracellular serotonin levels. This sustained increase eventually desensitizes 5-HT1A auto-receptors, which is critical for the full clinical effect of SSRIs.

Pharmacodynamics

As a selective serotonin re-uptake inhibitor, escitalopram increases serotonin levels in neuronal synapses, leading to an antidepressant effect. Compared to other SSRIs, escitalopram has a relatively quick onset of action due to its potency. The drug has been associated with potential adverse effects such as abnormal bleeding and serotonin syndrome, particularly when used with other serotonergic drugs. Abrupt discontinuation may lead to withdrawal symptoms, necessitating a gradual tapering of the dose.

Pharmacokinetics

Escitalopram is well absorbed after oral administration, with peak plasma concentrations typically reached within 4-6 hours. It has a volume of distribution of approximately 12 L/kg and is highly protein-bound. The drug undergoes extensive hepatic metabolism, primarily via the cytochrome P450 enzyme CYP2C19, and has a half-life of about 27-32 hours, allowing for once-daily dosing. Renal impairment does not significantly affect the pharmacokinetics of escitalopram, but caution is advised in hepatic impairment.

Contra-indications

• QT-interval prolongation
• concurrent use of monoamine oxidase inhibitors (MAOIs)
• hypersensitivity to escitalopram or any of its excipients

Adverse effects

• nausea
• somnolence
• insomnia
• dry mouth
• sweating
• dizziness
• sexual dysfunction
• increased risk of bleeding
• serotonin syndrome

Interactions

• moclobemide + escitalopram: Moderate (increases exposure)
• other serotonergic drugs (risk of serotonin syndrome)
• anticoagulants (increased risk of bleeding)

Precautions

• use with caution in patients with a history of seizures
• monitor for signs of serotonin syndrome
• gradual tapering recommended to avoid discontinuation syndrome
• consider risks in patients with hepatic impairment

Pregnancy

Escitalopram should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Data suggest potential risks including fetal cardiac defects.

Breast-feeding

Present in breast milk; use with caution and consider alternative treatments if necessary.

Storage

Store at room temperature, away from moisture and heat. Keep container tightly closed.

Formulations

• Citalopram 40 mg/ml oral drops, sugar-free
• Citalopram 10 mg tablets
• Citalopram 20 mg tablets
• Citalopram 40 mg tablets

Mechanism of action

Escitalopram, like other selective serotonin re-uptake inhibitors, enhances serotonergic activity by binding to the orthosteric (i.e. primary) binding site on the serotonin transporter (SERT), the same site to which endogenous 5-HT binds, and thus prevents the re-uptake of serotonin into the presynaptic neuron. Escitalopram, along with [paroxetine], is also considered an allosteric serotonin re-uptake inhibitor - it binds to a secondary allosteric site on the SERT molecule to more strongly inhibit 5-HT re-uptake. Its combination of orthosteric and allosteric activity on SERT allows for greater extracellular 5-HT levels, a faster onset of action, and greater efficacy as compared to other SSRIs. The sustained elevation of synaptic 5-HT eventually causes desensitization of 5-HT_1A auto-receptors, which normally shut down endogenous 5-HT release in the presence of excess 5-HT - this desensitization may be necessary for the full clinical effect of SSRIs and may be responsible for their typically prolonged onset of action. Escitalopram has shown little-to-no binding affinity at a number of other receptors, such as histamine and muscarinic receptors, and minor activity at these off-targets may explain some of its adverse effects. The mechanism of antidepressant action of escitalopram, the S-enantiomer of racemic citalopram, is presumed to be linked to potentiation of serotonergic activity in the central nervous system (CNS) resulting from its inhibition of CNS neuronal reuptake of serotonin (5-HT).

Pharmacodynamics

Escitalopram belongs to a class of medications called selective serotonin re-uptake inhibitors (SSRIs). These agents cause an increase in serotonin levels in neuronal synapses by preventing the re-uptake of serotonin (5-HT) into the presynaptic terminals of serotonergic neurons. As compared to other SSRIs, it appears to have a relatively quick onset of effect due to its potency. SSRIs as a class have been associated with abnormal bleeding, particularly in patients receiving concomitant therapy with other medications affecting hemostasis, and with the development of serotonin syndrome. Use escitalopram with caution in patients with a higher-than-baseline risk of bleeding and in patients receiving concomitant therapy with other serotonergic drugs. Escitalopram may also cause a discontinuation syndrome with abrupt removal of the drug, and should be slowly tapered if discontinuation of therapy is warranted.