Amitriptyline

Class: Tricyclic antidepressant

Indications: Depression, neuropathic pain, migraine prophylaxis

Contraindications/cautions: Recent MI or heart block; urinary retention without urinary catheter insitu; angle-closure glaucoma. Caution in epilepsy; bipolar disorder, suicidal ideation.

Adverse reactions: common: Constipation, dry mouth, blurred vision, sedation (increased in hepatic impairment); less common: photophobia, urinary retention, tachycardia, confusion, delirium, postural hypotension, sweating, QT-prolongation.

Metabolism/clearance: metabolised to nortriptyline by CYP2C19 and CYP2C8/9 in the liver. Negligible renal clearance.

Interactions: serotonin syndrome with other serotonergic drugs (caution); QT-prolonging drugs, MAOI’s (contraindicated)

Dosing:
oral: neuropathic pain: 10 mg at night – increase gradually to 25 to 50 mg at night. Maximum 75 mg but rarely tolerated in palliative patients
subcut: N/A
rectal: N/A

Syringe driver: N/A

Mechanism of action: analgesic effects may be through noradrenaline & serotonin pathways – also opioid agonism, alpha adrenoreceptor blockade and ion channel blockade to reduce transmission.

Half life: 15 hours (metabolite nortriptyline half life of 30 hours)

Onset: oral: can take a few weeks or up to 6 weeks for full effect vs pain

Notes: lower doses used for pain; higher doses used in depression. Tablets may be film coated – can be halved and likely to be able to be crushed

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