AMITRIPTYLINE TABLETS (Each tablet contains 25mg)

Indications

• Major depressive disorder
• Generalized anxiety disorder
• Neuropathic pain
• Chronic pain syndromes
• Migraine prophylaxis
• Insomnia related to depression

Dosage

Children: Refer to the BNF for Children for specific pediatric dosing recommendations.

Adults: Refer to the BNF for specific dosing guidelines based on the condition being treated.

Mechanism of action

Amitriptyline primarily acts by inhibiting the reuptake of norepinephrine and serotonin at the presynaptic neuronal membrane, increasing the availability of these neurotransmitters in the synaptic cleft. It also has antagonistic effects on various receptors including histaminergic (H1), muscarinic, and alpha-adrenergic receptors, which contribute to its side effects and therapeutic effects.

Pharmacodynamics

Amitriptyline exhibits a complex pharmacodynamic profile, characterized by its antidepressant effects as well as analgesic properties for certain types of pain. It has a sedative effect due to its antihistaminic activity, which can be beneficial in patients with insomnia related to depression. The blockade of muscarinic receptors contributes to anticholinergic side effects such as dry mouth, constipation, and blurred vision.

Pharmacokinetics

Amitriptyline is well absorbed from the gastrointestinal tract, with peak plasma concentrations typically occurring within 2 to 12 hours after oral administration. It undergoes extensive first-pass metabolism in the liver, primarily by cytochrome P450 enzymes, leading to the formation of active metabolites, including nortriptyline. The elimination half-life ranges from 10 to 50 hours, allowing for once-daily dosing in many cases. It is highly protein-bound (approximately 95%) and has a large volume of distribution, indicating extensive tissue uptake.

Contra-indications

• Hypersensitivity to amitriptyline or any of its components
• Concurrent use with monoamine oxidase inhibitors (MAOIs)
• Acute recovery phase after myocardial infarction
• Prolonged QT interval or other significant cardiac arrhythmias

Adverse effects

• Sedation
• Dry mouth
• Constipation
• Urinary retention
• Blurred vision
• Weight gain
• Dizziness
• Orthostatic hypotension
• Tachycardia
• Arrhythmias
• Serotonin syndrome (when used with other serotonergic agents)

Interactions

• Increased sedation with alcohol or other central nervous system depressants
• Increased risk of serotonin syndrome with SSRIs, SNRIs, or other serotonergic drugs
• Increased anticholinergic effects with other anticholinergic agents
• May enhance the effects of antihypertensives
• May affect the metabolism of drugs metabolized by cytochrome P450 enzymes, particularly CYP2D6

Precautions

• Use with caution in patients with a history of seizures
• Caution in patients with a history of bipolar disorder
• Monitor for signs of suicidal ideation, especially in younger patients
• Use cautiously in patients with hepatic or renal impairment
• Caution in elderly patients due to increased sensitivity to side effects

Pregnancy

Amitriptyline should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is classified as category C.

Breast-feeding

Amitriptyline is excreted in breast milk. Caution is advised when administering to nursing mothers.

Storage

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

Formulations

• Tablets
• Oral solution
• Injectable form