MENELAT 45

Indications

• Major depressive disorder
• Generalized anxiety disorder
• Post-traumatic stress disorder
• Insomnia associated with depression

Dosage

Children: Refer to the BNF for Children for specific dosing guidelines.

Adults: Refer to the BNF for specific dosing guidelines.

Mechanism of action

Mirtazapine acts as an antagonist at central alpha-2 adrenergic receptors, which enhances the release of norepinephrine and serotonin in the synaptic cleft. It also antagonizes the 5-HT2 and 5-HT3 serotonin receptors while being a potent agonist at the 5-HT1A receptor, promoting serotonergic neurotransmission. This multifaceted activity contributes to its antidepressant effects.

Pharmacodynamics

The pharmacodynamics of mirtazapine involve its effects on neurotransmitter systems. By blocking presynaptic alpha-2 adrenergic receptors, it increases the availability of norepinephrine and serotonin. The blockade of 5-HT2 and 5-HT3 receptors reduces anxiety and gastrointestinal side effects, respectively. The overall result is an improvement in mood, reduction in anxiety, and a sedative effect due to antihistaminergic activity.

Pharmacokinetics

Mirtazapine is well absorbed after oral administration, with peak plasma concentrations occurring within 2 hours. It has a bioavailability of approximately 50%, and its plasma half-life is around 20 to 40 hours, allowing for once-daily dosing. Mirtazapine is extensively metabolized by the liver, primarily through CYP2D6, CYP1A2, and CYP3A4 enzymes, with renal excretion of metabolites.

Contra-indications

• Hypersensitivity to mirtazapine or any of its components
• Concurrent use with monoamine oxidase inhibitors (MAOIs)
• History of agranulocytosis

Adverse effects

• Sedation
• Increased appetite and weight gain
• Dizziness
• Dry mouth
• Constipation
• Fatigue
• Rarely, agranulocytosis
• Serotonin syndrome (when used with serotonergic drugs)

Interactions

• Increased sedation when used with alcohol, benzodiazepines, or other central nervous system depressants
• Potential interaction with other antidepressants, particularly those affecting serotonin levels
• Caution with concomitant use of drugs that are known to inhibit cytochrome P450 enzymes

Precautions

• Monitor for signs of suicidal thoughts or behavior, particularly in young adults
• Use with caution in patients with a history of seizures
• Caution in patients with hepatic or renal impairment

Pregnancy

Mirtazapine should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Consult with a healthcare provider.

Breast-feeding

Mirtazapine is excreted in breast milk, and caution is advised when administering to nursing mothers. Consult with a healthcare provider.

Storage

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

Formulations

• Oral tablets (15 mg, 30 mg, 45 mg)
• Orally disintegrating tablets (15 mg, 30 mg, 45 mg)