Amitriptyline

BRAND NAMES

Common brand names for amitriptyline include:

• Amitid

• Amitone

• Amitril

• Elavil (brand discontinued in the U.S., but often used generically)

• Endep (brand discontinued in the U.S.)

• Levate

• Sarotena

• Tryptanol

• Tryptomer

• Vanatrip 

Amitriptyline is also found in combination products with other medications under brand names such as Limbitrol (with chlordiazepoxide) and Triavil (with perphenazine). 

MECHANISM OF ACTION

Amitriptyline acts by inhibiting the reuptake of serotonin and norepinephrine in the brain, increasing their levels in the synaptic cleft. This enhances neurotransmission involved in mood regulation. It also blocks muscarinic, histamine H₁, and alpha-1 adrenergic receptors, which contributes to its sedative effects and side effects.

PHARMACOKINETICS

Absorption

Amitriptyline is quickly and efficiently absorbed from the gastrointestinal tract after oral intake, but extensive first-pass hepatic metabolism significantly reduces its bioavailability, which averages around 50% and typically ranges between 30% and 60%.

Distribution

Amitriptyline has a large volume of distribution, with reported values generally ranging from 16 to 22 L/kg.

Metabolism

Amitriptyline is extensively metabolized during its first pass through the liver, mainly by cytochrome P450 enzymes particularly CYP2C19 and CYP2D6 resulting in the formation of both active and inactive metabolites.

Excretion

Amitriptyline is eliminated mainly through the kidneys, primarily in the form of metabolites, with only a small amount excreted unchanged in the urine. A minor portion is also excreted via the bile and feces. Renal excretion depends on urine pH, with increased elimination in acidic urine.

PHARMACODYNAMICS

Amitriptyline is a tricyclic antidepressant (TCA) that exhibits a multimodal pharmacodynamic profile, mainly through inhibition of serotonin and norepinephrine reuptake in the central nervous system. This leads to increased levels of these neurotransmitters in the synaptic cleft, contributing to its antidepressant and pain-relieving effects.

DOSAGE AND ADMINISTRATION

• Administered orally as tablets or liquid.

• Initial dose for depression: 25–50 mg/day.

• Maintenance dose: 100–150 mg/day in divided doses or at bedtime.

• For chronic/neuropathic pain or migraine: 10–25 mg at bedtime.

• Dose increased gradually based on response and tolerance.

• Lower doses recommended for elderly patients.

• Adjust dose in hepatic impairment.

• Avoid sudden discontinuation; taper gradually.

DRUG INTERACTIONS

Amitriptyline interacts with several drugs. Combining it with MAO inhibitors or other serotonergic drugs can cause serious reactions like serotonin syndrome. CYP2D6 inhibitors may raise its levels, increasing toxicity risk. Alcohol, CNS depressants, and other anticholinergic or QT-prolonging drugs can worsen sedation, side effects, or heart rhythm problems. Antihypertensives may have reduced effect or cause low blood pressure.

FOOD INTERACTIONS

Amitriptyline can be taken with or without food, as no major food interactions are known. However, some foods, beverages, or supplements may affect the medication, so it’s important to discuss these with a healthcare provider.

CONTRAINDICATIONS

Amitriptyline is contraindicated in individuals with hypersensitivity to TCAs, recent heart attack or severe cardiac conditions, concurrent or recent MAOI use, narrow-angle glaucoma, severe liver disease, or serious urinary retention, as its use in these situations can lead to dangerous complications.

SIDE EFFECTS

Common Side Effects:

• Mouth and Throat: Dry mouth (the most frequent side effect), unpleasant taste, or a "black tongue".

• Digestive System: Constipation, nausea, vomiting, or diarrhea.

• Neurological: Drowsiness, fatigue, dizziness (especially when standing up), and headaches.

• Vision: Blurred vision or difficulty focusing.

• Weight: Changes in appetite and weight gain.

• Physical Sensations: Numbness or tingling (pins and needles) in the hands and feet. 

Serious Side Effects:

• Heart Problems: Fast or irregular heartbeats, chest pain, palpitations, or fainting.

• Mental Health: Emergence or worsening of suicidal thoughts, irritability, aggression, or hallucinations.

• Urinary Issues: Difficulty passing urine or complete inability to pee.

• Severe Allergic Reaction: Swelling of the face, lips, or tongue; hives; or trouble breathing.

• Eye Issues: Severe eye pain, swelling, or redness (potential signs of glaucoma).

• Metabolic/Liver: Yellowing of the skin or eyes (jaundice), dark urine, or extreme weakness from low sodium levels.

OVERDOSE

• Neurological effects.

• Cardiac issues.

• Anticholinergic signs.

• Respiratory problems.

TOXICITY

Amitriptyline toxicity occurs when excessive amounts affect the central nervous system and cardiovascular system. It may lead to symptoms such as severe drowsiness, confusion, agitation, seizures, and dangerous heart rhythm disturbances. Toxicity can develop rapidly and is life‑threatening, requiring urgent medical care. Early recognition and prompt treatment are essential to reduce complications.