Desyrel (Trazodone). Dosage, Side Effects, Interactions
Desyrel (Trazodone) is an antidepressant that also has a sedative effect. The active ingredient is approved in adults for the treatment of depressive disorders with and without anxiety disorders.
Desyrel (Trazodone) is approved in adults for the treatment of depressive disorders with and without anxiety disorders. Use in children and adolescents under 18 years of age is not recommended. It is sometimes used to relieve inorganic erectile dysfunction associated with depression . At low doses, it is also used “off-label” to treat insomnia.
How Desyrel (Trazodone) works
The antidepressant effect of trazodone is based on a dual-serotonergic principle of action. Trazodone inhibits presynaptic serotonin reuptake and thus increases the supply of freely available serotonin at the synaptic cleft. At the same time, it postsynaptically blocks 5HT2A receptors, which are associated with anxiety, restlessness and insomnia. A strong affinity for central alpha1-receptors and the relatively weak antagonistic affinity for H1-receptors are probably responsible for the sedative properties of trazodone.
In addition to the antidepressant and anxiolytic effect, the active ingredient increases libido and erectile potency. The underlying mechanism of action is unclear. Anti-alpha1-, anti-alpha2-adrenergic and antiserotonergic mechanisms in the periphery and in the central nervous system are discussed.
There is no significant affinity for β-adrenergic, histaminergic H2, dopaminergic and cholinergic receptors.
After oral administration, trazodone is absorbed relatively quickly and almost completely absorbed. Oral, intramuscular and intravenous applications proved to be practically identical in terms of their AUC. The invasion half-life was 0.1 h for intramuscular application and between 0.3 h and 1.1 h for oral application. A steady state was achieved after 4 days by repeated administration of 25 mg.
The protein binding is given as 89-95%. After metabolization, the active substance is eliminated by the kidneys to about 70%. The remainder is excreted in the faeces.
In addition to other metabolites, the active metabolite 1-(3-chlorophenyl)piperazine, which has a pronounced serotonin agonistic effect, is also found in plasma. In terms of quantity, however, this is less than 1%.
The elimination half-life is subject to strong group-specific fluctuations. It was given as an average of 4.9 h for young males, 8.2 h for older males, 5.5 h for young females and 7.1 h for older females.
Impairment of renal function probably does not result in significant differences in serum concentrations. Dose adjustments are usually not necessary.
Dosage of Desyrel (Trazodone)
Trazodone is available in tablet form. The dosage and the duration of the application must be based on the individual situation, the indication and the severity of the disease. Therapy is initiated by gradually increasing the dose and ending therapy by slowly reducing the dose.
The dosage recommendations for outpatient and inpatient therapy as well as for selected patient groups can be found in the respective product information.
Side effects of Desyrel (Trazodone)
Fatigue, dizziness, gastrointestinal complaints and dry mouth, sleep disturbances, headaches, drop in blood pressure, orthostatic hypotension and restlessness are to be expected, particularly at the start of treatment. There may be an increase in these symptoms if trazodone is taken before meals.
Cases of suicidal ideation and behavior have been reported during trazodone treatment or early after treatment cessation.
Liver damage (sometimes serious) has been reported rarely. If such effects occur, trazodone should be discontinued immediately.
Trazodone side effects are listed below according to how common they are:
- sleep disorders
- Dizziness, headache, restlessness
- Cardiac arrhythmias (e.g. bradycardia, tachycardia, ventricular arrhythmias), particularly in patients with pre-existing arrhythmias
- orthostatic drop in blood pressure / hypotension
- Gastrointestinal symptoms (e.g. nausea, vomiting, diarrhoea), dry mouth
- confusional states
- visual disturbances (e.g. blurred vision)
- blood pressure increase
- Hypersensitivity reactions, e.g. B. Rash
- weight gain, weight loss.
- Dyscrasia (eg, anemia, thrombocytopenia, leukopenia/ neutropenia , agranulocytosis, pancytopenia)
- Epileptic seizures , symptoms in the sense of a serotonin syndrome / neuroleptic malignant syndrome, eg sweating, diarrhea, fever, blood pressure fluctuations, tachycardia, agitation, rigidity, disturbances of consciousness
- collapse states
- Liver dysfunction with transaminase elevation, hyperbilirubinemia, jaundice, hepatitis
- urticaria , angioedema.
Side effects with unknown frequency:
- allergic reaction
- Hyperprolactinaemia, Syndrome of Inappropriate ADH Secretion (SIADH)
- loss of appetite, increased appetite
- insomnia, anxiety, nervousness, agitation (very rarely aggravated to delirium), delusion,
- aggressive reaction
- Hallucinations, nightmares
- decreased libido, withdrawal symptoms
- Cases of suicidal thoughts or behavior
- mania / hypomania
- Drowsiness, decreased alertness, impaired memory, drowsiness, somnolence
- myoclonus, expressive aphasia, paraesthesia, dystonia,
- altered taste
- Palinopsia (visual disturbance with afterimages)
- Palpitations, ventricular arrhythmias, ventricular couplets, ventricular tachycardia (especially in the case of overdose and the presence of other risk factors, the QT interval in the ECG can be prolonged and torsades de pointes can occur)
- stuffy nose, shortness of breath
- Dyspepsia, abdominal pain, gastroenteritis, hypersalivation, paralytic ileus
- Liver function abnormalities (including jaundice and liver damage), intrahepatic cholestasis
- increased liver enzymes
- Pruritus, hyperhidrosis
- Pain in extremities, back pain, muscle pain, joint pain
- voiding dysfunction
- malaise, weakness
- Edema, peripheral edema
- flu-like symptoms, chest pain, fever.
If a long-term high-dose therapy is stopped quickly, withdrawal symptoms such as restlessness, sweating, nausea, vomiting and sleep disorders can occur.
The sedative effect of neuroleptics , hypnotics, sedatives, anxiolytics and antihistamines can be enhanced. In such cases, a dose reduction is recommended.
Oral contraceptives, phenytoin , carbamazepine and barbiturates speed up the metabolism of antidepressants . On the other hand, cimetidine and some other antipsychotics inhibit the metabolism of antidepressants.
Potent CYP3A4 inhibitors such as erythromycin , ketoconazole , itraconazole , ritonavir , indinavir and nefazodone are likely to lead to a marked increase in trazodone plasma concentrations. Concomitant administration of trazodone and potent CYP3A4 inhibitors should be avoided whenever possible. If concomitant use is required, a dose reduction of trazodone should be considered.
Concomitant use of carbamazepine results in low plasma concentrations of trazodone and its active metabolite meta-chlorophenylpiperazine. Patients should be closely monitored to determine if an increase in the dose of trazodone is necessary.
Concurrent administration of tricyclic antidepressants should be avoided. If necessary, attention should be paid to the occurrence of serotonin syndrome and cardiovascular side effects.
Rarely, increased plasma concentrations of trazodone and side effects have been reported when trazodone was co-administered with the CYP1A2/2D6 inhibitor fluoxetine . In addition to pharmacokinetic interactions, the occurrence of a serotonin syndrome is possible.
Severe orthostatic hypotension has been observed with concomitant use of phenothiazines such as chlorpromazine , fluphenazine , levomepromazine and perphenazine .
The effects of muscle relaxants and volatile anesthetics can be potentiated by trazodone and special caution is advised.
The toxicity of trazodone increases cumulatively if alcohol is consumed at the same time or other psychotropic drugs are taken. Trazodone, in turn, increases the sedative effects of alcohol. Alcohol should therefore be avoided during treatment with trazodone.
Antidepressants can speed up the metabolism of levodopa .
Concomitant use of trazodone and antihypertensive medicinal products may require a reduction in the antihypertensive medicinal product dose since treatment with trazodone may result in hypotension including orthostatic syndrome and syncope.
Concomitant use of trazodone and agents that prolong the QT interval (eg, class IA or III antiarrhythmics, antibiotics , antimalarials , antihistamines , neuroleptics) may increase the risk of ventricular arrhythmias such as torsades de pointes. Caution should be exercised when co-administering these drugs and trazodone.
St. John’s wort preparations can lead to an increased occurrence of side effects.
Concomitant use of trazodone and warfarin may alter prothrombin time. Caution is advised and blood coagulation levels should be carefully monitored.
Use of trazodone with digoxin or phenytoin may result in increased serum levels of digoxin or phenytoin. Monitoring of serum levels should be considered here.
With concomitant administration of other serotonergic agents, e.g. B. serotonin reuptake inhibitors , tricyclic antidepressants and neuroleptics are interactions in the sense of a serotonin syndrome / malignant neuroleptic syndrome possible. Fatal neuroleptic malignant syndromes have been reported, particularly with concomitant administration of neuroleptics for which this syndrome is a known potential adverse effect.
Trazodone is contraindicated in:
- Hypersensitivity to the active substance
- Acute intoxication with CNS depressants (e.g. analgesics and psychotropic drugs)
- carcinoid syndrome
- treatment with MAO inhibitors and within 2 weeks after stopping them
- alcohol intoxication
- acute myocardial infarction .
Available data from a limited number of pregnancies (< 200) do not indicate any adverse effects of trazodone on the course of pregnancy or the health of the foetus/newborn. Other relevant epidemiological data are not yet available. Animal studies at therapeutic doses do not indicate harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development.
Caution is advised when pregnant women take trazodone until delivery. The newborns should then be observed for the occurrence of withdrawal symptoms.
Excretion of trazodone in breast milk is likely to be low. However, the concentrations of the active metabolite are not known. Due to insufficient data, the benefit of breastfeeding for the child and the benefit of trazodone treatment for the mother should be weighed against each other.
Trazodone has minor to moderate influence on the ability to drive and use machines. Patients should be warned of the risk of driving or operating machinery if they experience drowsiness, sedation, dizziness, confusion or blurred vision.
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