Trazodone

Structural formula
General
Non-proprietary name	Trazodone
other names	2- {3- [4- (3-chlorophenyl) piperazin-1-yl] propyl} [1,2,4] triazolo [4,3 - "a"] pyridin-3-one ( IUPAC ) ; 2- {3- [4- (3-chlorophenyl) -1-piperazinyl] propyl} [1,2,4] triazolo [4,3 - "a"] pyridine-3 (2 "H") -on; Trazodonum ( Latin ) ;
Molecular formula	C 19 H 22 ClN 5 O
External identifiers / databases
ECHA InfoCard	100.039.364
PubChem	5533
DrugBank	DB00656
Wikidata	Q411457
Drug information
ATC code	N06 AX05
Drug class	Antidepressants
Mechanism of action	Serotonin reuptake inhibitors and the like Antagonist of the 5-HT 2 receptors
properties
Molar mass	371.86 g · mol -1
Melting point	87 ° C ; 222–228 ° C (hydrochloride, decomposition) ;
pK s value	6.14 (50% ethanol )
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
H and P phrases	H: 302-351
	P: 281
Toxicological data	690 mg kg −1 ( LD 50 , rat , oral )
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Trazodone is a drug from the group of psychotropic drugs . Because of its sedating and antidepressant effects, trazodone is used to treat sleep disorders , depression with or without accompanying anxiety disorder, and erectile dysfunction associated with depression without serious organic causes.

pharmacology

Trazodone is a serotonin reuptake inhibitor as well as an antagonist of the 5-HT ₂ receptors , the activation of which is generally associated with insomnia, anxiety, psychomotor restlessness and disorders of sexual function. In addition to nefazodone, it is therefore one of the dual serotonergic antidepressants (DSA). The inhibition of serotonin reuptake is relatively weak and, depending on the dose, only takes effect in higher doses. By blocking the 5-HT2a receptors, the serotonergic neurotransmission mediated by the 5-HT1A receptors is increased.

In addition, trazodone strongly inhibits the α1 and weakly the α2 and H1 receptors and has a weakening effect on the tremor . In contrast to other psychotropic substances, trazodone is not contraindicated in glaucoma and prostate problems. It has no extrapyramidal effect and does not increase adrenergic transmission. Trazodone also has no anticholinergic activity and is therefore free from a number of typical side effects of tricyclic antidepressants .

Use in humans

Trazodone is approved for the treatment of depressive illnesses with or without an anxiety component or sleep disorders in adults, as well as for the treatment of major depressive episodes in adults.

Trazodone is generally used when other lower-risk antidepressants remain ineffective or cannot be tolerated in a patient.

Trazodone is also used in off-label use as a sleep aid in non-depressed patients. Advantages of trazodone are said to be its good effect on sleep disorders even in low doses. Unlike many antidepressants, there is generally no weight gain or sexual dysfunction .

Side effects

Common side effects are dizziness, headache, dry mouth, increased tiredness, orthostatic dysregulation and cardiac arrhythmias . Rare but serious side effects are priapism , seizures and liver dysfunction as well as changes in the blood count ( agranulocytosis , thrombocytopenia , eosinophilia , leukopenia , pancytopenia ) and anemia.

Application restrictions

Trazodone must not be used in children and adolescents under 18 years of age. In this patient population, suicidal behavior and hostility were observed more frequently in clinical trials with antidepressants than with placebo. There are also no long-term data on safety in children and adolescents with regard to growth, maturation and cognitive and behavioral development.

The data on the safety of trazodone during pregnancy are limited and the possibility of trazodone being excreted in breast milk needs to be considered. Its use during pregnancy and breastfeeding should therefore be limited to selected cases after careful consideration by the doctor of the risk-benefit ratio. If trazodone is used until delivery, the newborn should be monitored for withdrawal symptoms. Trazodone can also lead to a prolongation of the QT time in the heart shortly after the start of therapy . This is a risk factor for threatening ventricular arrhythmias. Regular ECG controls should be carried out at the start of therapy. If the ECG shows an increase in the QT time, trazodone must be discontinued immediately. If possible, trazodone should not be combined with drugs that can also prolong the QT time or cause hypokalaemia.

Trazodone should not be combined with MAOIs . In combination with drugs that increase serotonergic transmission, the risk of central serotonin syndrome must be considered. Such drugs are e.g. B. SSRI , tramadol , tryptophan , 5-HTP .

Use in animals

In dogs, trazodone can be used against fear of noise. Sedation and vomiting on the following day were observed as side effects.

Commercial preparations

Human medicinal products: Trittico (A, CH); various generics in Germany.

Individual evidence

↑ ^a ^b Entry on trazodone in the ChemIDplus database of the United States National Library of Medicine (NLM) .
↑ Entry on trazodone. In: Römpp Online . Georg Thieme Verlag, accessed on March 10, 2014.
^ The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals, 14th Edition (Merck & Co., Inc.), Whitehouse Station, NJ, USA, 2006; ISBN 978-0-911910-00-1 .
↑ ^a ^b Data sheet Trazodone hydrochloride from Sigma-Aldrich , accessed on April 24, 2011 ( PDF ).
↑ Benkert, Otto; Hippius, Hans: Compendium of Psychiatric Pharmacotherapy . 10th edition. Springer, 2014, ISBN 978-3-642-54768-3 , pp. 71-73, 180-181 .
↑ ^a ^b ^c ^d Technical information Trittico 100 mg film-coated tablets, Angelini Pharma Austria GmbH. Status: January 2017.
↑ ^a ^b ^c ^d Technical information Trazodone Glenmark tablets, Glenmark Arzneimittel GmbH. As of May 2018.
↑ Tyrolean Society for General Medicine - News May 2014. (PDF) Accessed on May 18, 2018 .
↑ Tatjana Paola Harting, Jan-Peter Bach and Ingo Nolte: Effectiveness and side effects of dexmedetomidine and trazodone in a prospective, randomized and single-blind comparative study on the prophylaxis of acute noise anxiety in dogs (New Year's Eve study). In: Kleintierpraxis Volume 63, Issue 12, 2018, pp. 704–713.

[ChemIDplus-1] Entry on trazodone in the ChemIDplus database of the United States National Library of Medicine (NLM) .

[roempp-2] Entry on trazodone. In: Römpp Online . Georg Thieme Verlag, accessed on March 10, 2014.

[MERCK_Index-3] The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals, 14th Edition (Merck & Co., Inc.), Whitehouse Station, NJ, USA, 2006; ISBN 978-0-911910-00-1 .

[Sigma-4] Data sheet Trazodone hydrochloride from Sigma-Aldrich , accessed on April 24, 2011 ( PDF ).

[5] Benkert, Otto; Hippius, Hans: Compendium of Psychiatric Pharmacotherapy . 10th edition. Springer, 2014, ISBN 978-3-642-54768-3 , pp. 71-73, 180-181 .

[FI-AT-6] Technical information Trittico 100 mg film-coated tablets, Angelini Pharma Austria GmbH. Status: January 2017.

[FI-DE-7] Technical information Trazodone Glenmark tablets, Glenmark Arzneimittel GmbH. As of May 2018.

[8] Tyrolean Society for General Medicine - News May 2014. (PDF) Accessed on May 18, 2018 .

[9] Tatjana Paola Harting, Jan-Peter Bach and Ingo Nolte: Effectiveness and side effects of dexmedetomidine and trazodone in a prospective, randomized and single-blind comparative study on the prophylaxis of acute noise anxiety in dogs (New Year's Eve study). In: Kleintierpraxis Volume 63, Issue 12, 2018, pp. 704–713.