AMITRIP TABLETS

Indications

• Major depressive disorder
• Anxiety disorders
• Chronic pain syndromes
• Migraine prophylaxis
• Insomnia

Dosage

Children: Refer to the BNF for Children for appropriate pediatric dosing guidelines.

Adults: Refer to the BNF for specific dosing information, as doses vary based on the condition being treated.

Mechanism of action

Amitriptyline functions mainly as a serotonin-norepinephrine reuptake inhibitor (SNRI). It blocks the reuptake of the neurotransmitters serotonin and norepinephrine at the synaptic cleft, increasing their availability and enhancing mood and emotional response. Additionally, it antagonizes various receptors, including histamine H1 and muscarinic acetylcholine receptors, contributing to its side effect profile and therapeutic effects.

Pharmacodynamics

Amitriptyline's antidepressant effects typically manifest after several weeks of treatment as it alters neurotransmitter levels and receptor sensitivities in the brain. Its anticholinergic effects can lead to sedation and a reduction in anxiety, while its analgesic properties may be due to the modulation of pain pathways in the central nervous system. The drug's effects on sleep architecture, particularly its ability to increase total sleep time and reduce sleep latency, make it useful in treating insomnia.

Pharmacokinetics

Amitriptyline is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 4 to 12 hours post-administration. It undergoes extensive hepatic metabolism, primarily via cytochrome P450 enzymes, resulting in active metabolites such as nortriptyline. The drug has a long half-life, ranging from 10 to 50 hours, allowing for once-daily dosing. It is primarily excreted in urine, with both unchanged drug and metabolites present.

Contra-indications

• Hypersensitivity to amitriptyline or any of its components
• Recent myocardial infarction
• Concurrent use with monoamine oxidase inhibitors (MAOIs)
• Severe liver impairment
• Angle-closure glaucoma

Adverse effects

• Somnolence
• Dry mouth
• Constipation
• Urinary retention
• Blurred vision
• Weight gain
• Sexual dysfunction
• Orthostatic hypotension
• Tachycardia
• Cardiac arrhythmias

Interactions

• Increased sedation when combined with alcohol or other central nervous system depressants
• Potentially increased risk of serotonin syndrome when used with other serotonergic drugs
• Anticholinergic effects may be enhanced when used with other anticholinergic agents
• Concurrent use with MAOIs can lead to serious, potentially fatal reactions

Precautions

• Use with caution in patients with a history of seizures
• Careful monitoring is advised in patients with cardiovascular disease
• May cause increased suicidal thoughts or behavior in children, adolescents, and young adults
• Gradual dose reduction is recommended to avoid withdrawal symptoms

Pregnancy

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

Breast-feeding

Amitriptyline is excreted in breast milk. A decision should be made whether to discontinue breastfeeding or discontinue the drug.

Storage

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

Formulations

• Tablets
• Oral solution
• Injection