Products
Trazodone is commercially available in the form of film-coated tablets and sustained-release tablets (Trittico, Trittico retard, Trittico Uno). The active ingredient was developed at Angelini in Italy in 1966 and has been approved in many countries since 1985. Auto-generics and generics are registered. Generic versions of the 100 mg film-coated tablets first went on sale in many countries in 2018.
Structure and properties
Trazodone (C19H22ClN5O, Mr = 371.9 g/mol) is present in drugs as trazodone hydrochloride. It is a triazole pyridine and phenylpiperazine derivative and differs structurally from other antidepressants. Trazodone exists as a white, crystalline powder that is readily soluble in water.
Effects
Trazodone (ATC N06AX05) has antidepressant, sedative, and, in low doses, sleep-inducing properties. Effects are attributed in part to inhibition of serotonin reuptake into the presynaptic neuron and antagonism at 5-HT2 receptors. Trazodone belongs to the SARI, the . Sedative effects are rapid, whereas antidepressant effects take one to three weeks. According to the literature, trazodone is also an alpha blocker, which explains adverse effects such as low blood pressure and priapism. Unlike other antidepressants and neuroleptics, trazodone is neither anticholinergic nor antidopaminergic.
Indications
For the treatment of depression with or without anxiety disorder.
Off-label use
Because of its sedative-hypnotic properties, trazodone is commonly used off-label for the treatment of sleep disorders in nondepressed patients. However, the drug has not yet been approved by regulatory authorities for this use, and this practice is not without controversy. For a detailed discussion, see, for example, Mendelson (2005). In the context of depression, the treatment of sleep disorders is mentioned in the SmPC.
Dosage
According to the SmPC. The dose is adjusted individually and gradually. The drug can be taken as a single dose in the evening before bedtime. Administration in multiple doses is also possible, preferably immediately after meals. Discontinuation should be gradual.
Contraindications
- Hypersensitivity
- Children and adolescents under 18 years of age (insufficient experience).
- Intoxication with alcohol or sleeping pills
- Acute heart attack
Full precautions can be found in the drug label.
Interactions
Trazodone is a substrate of CYP3A4. Appropriate drug-drug interactions with CYP inhibitors or CYP inducers may occur. The effects of centrally depressant drugs and alcohol may be enhanced. Alcohol consumption should be avoided during treatment. Serotonin syndrome may develop when combined with serotonergic agents and MAO inhibitors. Other interactions have been described.
Adverse effects
The most common potential adverse effects include drowsiness, dry mouth, and limb, back, muscle, and joint pain.
See under
Antidepressants, sleeping pills, serotonin syndrome.
