CIT-20 TABLETS

Indications

• Major depressive disorder
• Generalized anxiety disorder
• Obsessive-compulsive disorder
• Panic disorder
• Social anxiety disorder

Dosage

Adults: For adults, the initial dose is typically 10 mg once daily, which may be increased as needed in increments of 10 mg, with a usual maintenance dose of 20-30 mg daily and a maximum

Mechanism of action

The mechanism of action of citalopram is presumed to be related to the potentiation of serotonergic activity in the central nervous system (CNS) due to its inhibition of the reuptake of serotonin (5-HT) through the serotonin transporter (SLC6A4). It binds with significantly less affinity to other receptors such as histamine, acetylcholine, and norepinephrine receptors, which contributes to its lower side effect profile compared to tricyclic antidepressants.

Pharmacodynamics

Citalopram is classified as an SSRI, which alleviates symptoms of depression, anxiety, and other mood disorders by inhibiting the reuptake of serotonin. This inhibition leads to increased serotonin levels in the synaptic cleft, which is crucial for mood regulation. The onset of therapeutic effects may take 1 to 4 weeks, with a complete response potentially taking 8 to 12 weeks. Chronic use has been shown to downregulate central norepinephrine receptors, similar to other effective antidepressants.

Pharmacokinetics

Citalopram is well-absorbed from the gastrointestinal tract, with a bioavailability of approximately 80%. It undergoes extensive hepatic metabolism, primarily via cytochrome P450 2C19, and has a half-life of about 35 hours. It is primarily excreted as metabolites in urine. The pharmacokinetics may be altered in patients with hepatic impairment, necessitating careful monitoring and potential dose adjustments.

Contra-indications

• QT-interval prolongation
• Hypersensitivity to citalopram or any excipients

Adverse effects

• Chills
• Abnormal dreams
• Insomnia
• Nausea
• Diarrhea
• Dry mouth
• Dizziness
• Fatigue
• Sexual dysfunction
• Increased sweating

Interactions

• Increased risk of serotonin syndrome when used with other serotonergic agents
• Increased risk of bleeding when used with anticoagulants and antiplatelet agents
• Caution with MAO inhibitors, caution with CYP2C19 and CYP3A4 inhibitors

Precautions

• Use with caution in patients with a history of seizure disorders
• Monitor for worsening depression or suicidal thoughts, particularly in younger patients
• Consider dose adjustments in hepatic impairment
• Avoid abrupt discontinuation to prevent withdrawal symptoms

Pregnancy

Citalopram should only be used in pregnancy if the potential benefit justifies the potential risk to the fetus. It may be associated with an increased risk of congenital malformations.

Breast-feeding

Citalopram is present in breast milk; use with caution in nursing mothers.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

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

Indications

• Respiratory conditions (e.g., asthma, chronic obstructive pulmonary disease)
• Cough (e.g., as an antitussive)
• Anxiety and sleep disorders (when associated with specific formulations)

Dosage

Children: Refer to the BNF for Children for appropriate dosing information, as it is determined based on weight and age for the specific formulation.

Adults: Refer to the specific product monograph for dosing information, as it varies based on the drug formulation and indication.

Mechanism of action

Hydrobromides often act as competitive antagonists or agonists at specific receptor sites, depending on the drug involved. The exact mechanism can vary widely, but many hydrobromide-containing drugs modulate neurotransmitter activity, impacting various pathways in the body such as those involved in the central nervous system or respiratory function. The metabolic pathways include Phase I reactions primarily mediated by cytochrome P450 enzymes, which facilitate the functionalization and clearance of these compounds.

Pharmacodynamics

The pharmacodynamics of hydrobromide salts are largely determined by the specific drug they are associated with. Generally, hydrobromides may exhibit effects such as sedation, bronchodilation, or antitussive actions. The efficacy and adverse effects are influenced by the drug's receptor selectivity, affinity, and the pharmacological properties inherent to the parent compound.

Pharmacokinetics

Hydrobromides typically exhibit variable pharmacokinetic profiles depending on the specific drug formulation. They are generally absorbed rapidly following oral administration, with peak plasma concentrations occurring within a few hours. Metabolism primarily occurs in the liver through cytochrome P450 enzymes, particularly CYP2E1, among others. The elimination half-life varies but is often in the range of several hours, allowing for once or twice-daily dosing in many formulations. Excretion is usually via the kidneys, with metabolites being eliminated in urine.

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Use only if clearly needed and the potential benefits justify the potential risks to the fetus.

Breast-feeding

Caution is advised; consider the importance of the drug to the mother against potential risks to the breastfeeding infant.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Mechanism of action

The mechanism of action of citalopram is unclear but is presumed to be related to potentiation of serotonergic activity in the central nervous system (CNS) resulting from its inhibition of CNS neuronal reuptake of serotonin (5-HT), potentially through the inhibition of the serotonin transporter (solute carrier family 6 member 4, _SLC6A4_). Citalopram binds with significantly less affinity to histamine, acetylcholine, and norepinephrine receptors than tricyclic antidepressant drugs. Particularly, citalopram has no or very low affinity for 5-HT_1A, 5-HT_2A, dopamine D₁ and D₂, α₁-, α₂-, and β-adrenergic, histamine H₁, gamma aminobutyric acid (GABA), muscarinic cholinergic, and benzodiazepine receptors. /In/ whole-cell patch clamp recording of heterologous HERG-mediated currents in transfected mammalian cells ... citalopram blocks HERG with an IC(50) of 3.97 uM. This is slightly less potent than fluoxetine in /the same/ system (IC(50) of 1.50 uM). In isolated guinea pig ventricular cardiomyocytes, citalopram inhibited L-type calcium current (I(Ca,L)). The voltage dependence of I(Ca,L) inactivation in the presence of 100 uM citalopram was shifted significantly leftward. As a result, the I(Ca,L) 'window' in citalopram was found to be smaller & leftward-shifted compared to control. /These/ effects ... may help to explain citalopram's good cardiac safety profile, given its propensity to block HERG at excessive dosages. /Salt not specified/ The study was aimed to investigate the effects of the minimal effective doses of acute citalopram (5 mg/kg), (+/-)-8-hydroxydipropylaminotetralin HBr (8-OH-DPAT; 0.1 mg/kg), & their combined treatment on the rat open field & forced swimming behaviour & post-mortem monoamine content. The animals were prospectively divided into the vehicle- and para-chlorophenylalanine (p-CPA)-pretreated (350 mg/kg) groups. Acute citalopram (5 mg/kg), 8-OH-DPAT (0.1 mg/kg), or their combined treatment had no major effect on the rat open field & forced swimming behaviour. The post-mortem catecholamine content in four brain regions studied was unchanged in all treatment groups. The combined 8-OH-DPAT (0.1 mg/kg) & citalopram (5 mg/kg) treatment partially reversed the p-CPA-induced decr of serotonin (5-HT) and 5-hydroxy-indolacetic acid (5-HIAA) content. The present experiments demonstrate that the 5-HT1A receptors mediate some of the selective serotonin reuptake inhibitor-induced biochemical phenomena.

Pharmacodynamics

Citalopram belongs to a class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs). It has been found to relieve or manage symptoms of depression, anxiety, eating disorders and obsessive-compulsive disorder among other mood disorders. The antidepressant, anti-anxiety, and other actions of citalopram are linked to its inhibition of CNS central uptake of serotonin. Serotonergic abnormalities have been reported in patients with mood disorders. Behavioral and neuropsychological effects of serotonin include the regulation of mood, perception, reward, anger, aggression, appetite, memory, sexuality, and attention, as examples. The onset of action for depression is approximately 1 to 4 weeks. The complete response may take 8-12 weeks after initiation of citalopram. <i>In vitro</i> studies demonstrate that citalopram is a strong and selective inhibitor of neuronal serotonin reuptake and has weak effects on norepinephrine and dopamine central reuptake. The chronic administration of citalopram has been shown to downregulate central norepinephrine receptors, similar to other drugs effective in the treatment of major depressive disorder. Citalopram does not inhibit monoamine oxidase.