Trazodone (Desyrel, Trittico, Thombran, Trialodine) is a psychoactive compound with sedative, anxiolytic, and antidepressant properties. The manufacturer claims that the antidepressant activity becomes evident in the first week of therapy. Trazodone has less prominent anticholinergic (dry mouth, constipation, tachycardia) and adrenolytic (hypotension, male sexual problems) side effects than most tricyclic antidepressants. The incidence of nausea and vomiting observed with Trazodone is relatively low compared to SSRIs.
Mechanism of action
Trazodone is a serotonin reuptake inhibitor and is also a 5-HT2 receptor antagonist. However, in contrast to the selective serotonin reuptake inhibitors such as fluoxetine (Prozac), trazodone's antidepressant effects may be due to the antagonism of 5-HT2 receptors
Trazodone is well absorbed after oral administration with mean peak plasma levels obtained at approximately 1 hour after ingestion. Absorption is somewhat delayed and enhanced by food. The mean plasma elimination half-life is biphasic: the first phase's half-life is 3-6 hours, and the following phase's half-life is 5-9 hours. The drug is extensively metabolized with 3 or 4 major metabolites having been identified in man. Approximately 70-75% of C14-labelled trazodone was found to be excreted in the urine within 72 hours (PMID 1037253). Trazodone is highly protein-bound.
Depression with or without anxiety
Chronic Insomnia (in some countries, this is an off-label use)
Known hypersensitivity to trazodone
Use in patients below 18 years of age
Trazodone is metabolised by CYP3A4, a liver enzyme (PMID 9616194). Inhibition of this enzyme by various other substances may delay its degradation, leading to high blood levels of trazodone. CYP3A4 may be inhibited by many other medications, herbs, and foods, and as such, trazodone may interact with these substances. One drug-food interaction is grapefruit juice. Drinking grapefruit juice is discouraged in patients taking trazodone.
One glass of grapefruit juice once in a while is not likely to have this effect on most people, but drinking large amounts, or drinking it regularly is proven to.
The possibility of suicide in depressed patients remains during treatment and until significant remission occurs. Therefore, the number of tablets prescribed at any one time should take into account this possibility, and patients with suicide ideation should never have access to large quantities of trazodone.
Episodes of complex partial seizures have been reported in a small number of patients. The majority of these patients were already receiving anticonvulsant therapy for a previously diagnosed seizure disorder.
Pregnancy and Lactation
Pregnancy : Sufficient data in humans is lacking. The use should be justified by the severity of the condition to be treated.
Lactation : Sufficient data in humans is also lacking. Additionally, trazodone may be found in the maternal milk in significant concentrations. The use in breastfeeding women should be carefully weighed against possible risks.
The most common adverse reactions encountered are drowsiness, nausea/vomiting, headache and dry mouth. Adverse reactions reported include the following:
Drowsiness, fatigue, lethargy, psychomotor retardation, lightheadedness, dizziness, difficulty in concentration, confusion, impaired memory, disorientation, excitement, agitation, anxiety, tension, nervousness, restlessness, insomnia, nightmares, anger, hostility and, rarely, hypomania, visual distortions, hallucinations, delusions and paranoia.
Tremor, headache, ataxia, akathisia, muscle stiffness, slurred speech, slowed speech, vertigo, tinnitus, tingling of extremities, paresthesia, weakness, complex partial seizures, and, rarely impaired speech, muscle twitching, numbness, dystonia and involuntary movements.
Dry mouth, blurred vision, diplopia, miosis, nasal congestion, constipation, sweating, urinary retention, increased urinary frequency and incontinence.
Orthostatic hypotension, hypertension, tachycardia, palpitations, shortness of breath, apnea, syncope, arrhythmias, prolonged P-R interval, atrial fibrillation, bradycardia, ventricular ectopic activity (including ventricular tachycardia), myocardial infarction and cardiac arrest.
Rare Side Effects
Recent clinical studies in patients with pre-existing cardiac disease indicate that trazodone may be arrhythmogenic in some patients in that population. Arrhythmias identified include isolated PVC's, ventricular couplets, and in 2 patients short episodes (3 to 4 beats) of ventricular tachycardia. There have also been several post-marketing reports of arrhythmias in trazodone-treated patients who have pre-existing cardiac disease and in some patients who did not have pre-existing cardiac disease. Until the results of prospective studies are available, patients with pre-existing cardiac disease should be closely monitored, particularly for cardiac arrhythmias. Trazodone is not recommended for use during the initial recovery phase of myocardial infarction.
Nausea, vomiting, diarrhea, gastrointestinal discomfort, anorexia, increased appetite.
Rare cases of idiosyncratic hepatotoxicity have been observed, possibly due to the formation of reactive metabolites (PMID 15978881).
Decrease and, more rarely, increase in libido, weight gain and loss, and rarely, menstrual irregularities, retrograde ejaculation and inhibition of ejaculation.
Elevated prolactin concentrations have been observed in patients taking trazodone (PMID 7673654).
Trazodone has been associated with the occurrence of priapism. In approximately 33% of the cases reported, surgical intervention was required and, in a portion of these cases, permanent impairment of erectile function or impotence resulted. Male patients with prolonged or inappropriate erections should immediately discontinue the drug and consult their physician. If the condition persists for more than 24 hours, it would be advisable for the treating physician to consult a urologist or appropriate specialist in order to decide on a management approach.
Allergic or toxic
Skin rash, itching, edema, and, rarely, hemolytic anemia, methemoglobinemia, liver enzyme alterations, obstructive jaundice, leukocytoblastic vasculitis, purpuric maculopapular eruptions, photosensitivity and fever.
Aching joints and muscles, peculiar taste, hypersalivation, chest pain, hematuria, red, tired and itchy eyes.
Since trazodone may impair the mental and/or physical abilities required for performance of potentially hazardous tasks, such as operating an automobile or machinery, the patient should be cautioned not to engage in such activities while impaired.
It is recommended that white blood cell and differential counts should be performed in patients who develop sore throat, fever, or other signs of infection or blood dyscrasia and trazodone should be discontinued if the white blood cell or absolute neutrophil count falls below normal.
Trazodone may enhance the response to alcohol and the effects of barbiturates and other CNS depressants and patients should be cautioned accordingly.
Increased serum digoxin and phenytoin levels have been reported to occur in patients receiving trazodone concurrently with either of those 2 drugs. Little is known about the interaction between trazodone and general anesthetics; therefore, prior to elective surgery, trazodone should be discontinued for as long as clinically feasible.
Because it is not known whether an interaction will occur between trazodone and MAO inhibitors, administration of trazodone should be initiated very cautiously with gradual increase in dosage as required, if an MAO inhibitor is given concomitantly or has been discontinued shortly before medication with trazodone is instituted.
Trazodone may cause hypotension including orthostatic hypotension and syncope; caution is required if it is given to patients receiving antihypertensive drugs and an adjustment in the dose of the antihypertensive medication may be required.
Because of the absence of experience, concurrent administration of electro-shock therapy should be avoided.
Treatment should be started with low initial doses of 75 to 150mg daily in divided doses or in an evening single dose. The dose may be increased slowly to a maximum of 300mg daily in ambulatory patients and to 600mg daily in hospitalized patients. Geriatric and emanciated patients should begin with 100mg daily; this dose may be slowly increased to 300mg. The duration of treatment should be at least one month.
Overdosage of trazodone may cause an increase in incidence or severity of any of the reported adverse reactions, e.g. hypotension and excessive sedation. Death by deliberate or accidental overdosage has been reported (PMID 15975258, PMID 11603256).
There is no specific antidote for trazodone. Management of overdosage should, therefore, be symptomatic and supportive. Any patient suspected of having taken an overdosage should be admitted to hospital as soon as possible and the stomach emptied by gastric lavage. Forced diuresis may be useful in facilitating elimination of the drug.
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