Amitriptyline

Key points

• Amitriptyline is a tricyclic antidepressant, and its label states it is for the relief of symptoms of depression.
• Amitriptyline’s label notes that the enzyme cytochrome P450 2D6 (debrisoquin hydroxylase) is less active in a subset of the population, who can reach higher than expected plasma concentrations of tricyclic antidepressants such as amitriptyline at usual doses.
• A syndrome resembling neuroleptic malignant syndrome has been very rarely reported after starting or increasing the dose of amitriptyline.
• MedlinePlus also lists other uses for amitriptyline, including post-herpetic neuralgia, the nerve pain that can persist after a shingles infection.

What amitriptyline is, and how its metabolism can be affected

Amitriptyline’s label states it is for the relief of symptoms of depression. MedlinePlus also lists other uses for amitriptyline, including post-herpetic neuralgia, the burning, stabbing nerve pain that can persist for months or years after a shingles infection.

Amitriptyline’s mechanism of action in man is not known, though its label notes that it inhibits the reuptake of norepinephrine and serotonin by neurons, which is believed by some to underlie its antidepressant activity. The label also notes that the enzyme cytochrome P450 2D6 (debrisoquin hydroxylase) is less active in a subset of the population, sometimes called poor metabolisers, who can reach higher than expected plasma concentrations of tricyclic antidepressants such as amitriptyline at usual doses.

Boxed warning: suicidality and antidepressant drugs

Amitriptyline’s label carries a boxed warning on suicidality and antidepressant drugs. It states that antidepressants showed an increased risk of suicidal thinking and behaviour in children, adolescents and young adults, in short-term studies of major depressive disorder and other psychiatric disorders, over placebo. In the same short-term studies, adults over 24 did not show that increase, and adults aged 65 and older showed a reduced risk. The warning calls for patients of all ages who start antidepressant therapy to be monitored appropriately and observed closely for clinical worsening, suicidality or unusual changes in behaviour. Amitriptyline tablets are not approved for use in paediatric patients.

Other safety information the label flags

The label separately describes a syndrome resembling neuroleptic malignant syndrome as very rarely reported after starting or increasing the dose of amitriptyline, with symptoms that have included muscle rigidity, fever, mental status changes, sweating, a rapid heart rate and tremor. MedlinePlus notes that amitriptyline may cause drowsiness and advises against driving or operating machinery until its effects are known.

Tryptizol: a regional name for amitriptyline

The Emirates Drug Establishment’s drug directory records Tryptizol 25 mg with amitriptyline hydrochloride as its tablet ingredient, a familiar regional name for readers who know the medicine this way.

Further reading

• AMITRIPTYLINE HYDROCHLORIDE tablet
• Amitriptyline: MedlinePlus Drug Information
• Tryptizol® 25mg - Drug Directory