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Trazodone, sold under many brand names worldwide,
Common side-effects include dry mouth, feeling faint, vomiting, and headache.
Trazodone was approved for medical use in the United States in 1981.
1 Medical uses
1.1 Depression
1.2 Insomnia
1.3 Non-approved uses
1.4 Available forms
2 Side effects
2.1 Suicide
2.2 Sedation
2.3 Heart
2.4 Priapism
2.5 Other
2.6 Pregnancy and lactation
3 Overdose
4 Interactions
5 Pharmacology
5.1 Pharmacodynamics
5.1.1 Correspondence to clinical effects
5.2 Pharmacokinetics
6 Chemistry
7 History
8 Society and culture
8.1 Generic names
8.2 Brand names
9 References
10 External links
Medical uses
Trazodone has the following medical uses:
Unipolar depression, with or without anxiety
Anxiety disorder
The primary use of trazodone is the treatment of major depression. Data from open and double-blind trials suggest the antidepressant efficacy of trazodone is comparable to that of amitriptyline, doxepin, and mianserin. Also, trazodone showed anxiolytic properties, low cardiotoxicity, and relatively mild side effects.
Because trazodone has minimal anticholinergic activity, it was especially welcomed as a treatment for geriatric patients with depression when it first became available. Three double-blind studies reported trazodone has antidepressant efficacy similar to that of other antidepressants in geriatric patients. However, a side effect of trazodone, orthostatic hypotension, which may cause dizziness and increase the risk of falling, can have devastating consequences for elderly patients; thus, this side effect, along with sedation, often makes trazodone less acceptable for this population, compared with newer compounds that share its lack of anticholinergic activity but not the rest of its side-effect profile. Still, trazodone is often helpful for geriatric patients with depression who have severe agitation and insomnia.
Many clinicians use low-dose trazodone as an alternative to benzodiazepines for the treatment of insomnia. Two recent reviews found that trazodone is the second most prescribed agent for insomnia, but as most studies have been limited to people with depression, few studies actually support trazodone’s use in primary insomnia.
Non-approved uses
Off-label uses and investigational uses are listed below:
Complex regional pain syndrome
Obsessive–compulsive disorder (OCD)
Alcohol withdrawal
Schizophrenia as an adjunct to improve negative symptoms
Erectile dysfunction
Available forms
Trazodone is available in the form of 50 mg, 100 mg, 150 mg, and 300 mg tablets for oral ingestion.
Side effects
See also: List of adverse effects of trazodone
Because of its lack of anticholinergic side effects, trazodone is especially useful in situations in which antimuscarinic effects are particularly problematic (e.g., in patients with benign prostatic hyperplasia, closed-angle glaucoma, or severe constipation). Trazodone’s propensity to cause sedation is a dual-edged sword. For many patients, the relief from agitation, anxiety, and insomnia can be rapid; for other patients, including those individuals with considerable psychomotor retardation and feelings of low energy, therapeutic doses of trazodone may not be tolerable because of sedation. Trazodone elicits orthostatic hypotension in some people, probably as a consequence of α 1 -adrenergic receptor blockade. The unmasking of bipolar disorder may occur with trazodone
Precautions for trazodone include known hypersensitivity to trazodone and under 18 years and combined with other antidepressant medications, it may increase the possibility of suicidal thoughts or actions.
Trazodone has been reported to cause seizures in a small number of patients who took it concurrently with medications to control seizures.
While trazodone is not a true member of the SSRI class of antidepressants, it does still share many properties of the SSRIs, especially the possibility of discontinuation syndrome if the medication is stopped too quickly. Care must, therefore, be taken when coming off the medication, usually by a gradual process of tapering down the dose over a period of time.
The possibility of suicide in depressed people remains during treatment and until remission occurs. The number of tablets prescribed at any one time should take into account this possibility, and people with suicidal ideation should not have access to large quantities of trazodone.
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. Compared to the reversible MAOI antidepressant drug moclobemide, more impairment of vigilance occurs with trazodone.
Case reports have noted cardiac arrhythmias emerging in relation to trazodone treatment, both in patients with pre-existing mitral valve prolapse and in patients with negative personal and family histories of cardiac disease.
QT prolongation has been reported with trazodone therapy. Arrhythmia identified include isolated PVCs, ventricular couplets, and in two patients short episodes (three to four beats) of ventricular tachycardia. Several post-marketing reports have been made of arrhythmia 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. Concomitant administration of drugs that prolong the QT interval or that are inhibitors of CYP3A4 may increase the risk of cardiac arrhythmia.
A relatively rare, but dramatic, side effect associated with trazodone is priapism, likely due to its antagonism at α-adrenergic receptors.
Rare cases of liver toxicity have been observed, possibly due to the formation of reactive metabolites.
Elevated prolactin concentrations have been observed in people taking trazodone.
Pregnancy and lactation
Sufficient data in humans are lacking. Use should be justified by the severity of the condition to be treated.
There are reported cases of high doses of trazodone precipitating serotonin syndrome.
Trazodone appears to be relatively safer than TCAs, MAOIs, and a few of the other second-generation antidepressants in overdose situations, especially when it is the only agent taken. Fatalities are rare, and uneventful recoveries have been reported after ingestion of doses as high as 6,000–9,200 mg. In one report, 9 of 294 cases of overdose were fatal, and all nine patients had also taken other central nervous system (CNS) depressants. When trazodone overdoses occur, clinicians should carefully monitor for low blood pressure, a potentially serious toxic effect. In a report of a fatal trazodone overdose, torsades de pointes and complete atrioventricular block developed, along with subsequent multiple organ failure, with a trazodone plasma concentration of 25.4 mg/L on admission.
There is no specific antidote for trazodone. Management of overdosage should, therefore, be symptomatic and supportive. Any person suspected of having taken an overdosage should be evaluated at a hospital as soon as possible. Activated charcoal, and forced diuresis may be useful in facilitating elimination of the drug, gastric lavage has been shown to not be useful unless done during the first hour after intake.
Trazodone is metabolized by CYP3A4, a liver enzyme. 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.
Trazodone (and metabolite)
5-HT 1A
5-HT 1B
5-HT 1D
5-HT 1E
5-HT 1F
5-HT 2A
5-HT 2B
5-HT 2C
5-HT 3
5-HT 4
5-HT 5A
5-HT 6
5-HT 7
α 1
   α 1A
   α 1B
   α 1D
α 2
   α 2A
   α 2B
   α 2C
   β 1
   β 2
D 1
D 2
D 3
D 4
D 5
H 1
H 2
H 3
Guinea pig
H 4
σ 1
σ 2
I 1
NMDAR (MK-801)
Values are K i (nM). The smaller the value, the more strongly the drug binds to the site.
Trazodone is generally described as acting as a potent serotonin 5-HT 2A and α 1 -adrenergic receptor antagonist, a weak serotonin reuptake inhibitor (SRI), and a weak antihistamine or histamine H 1 receptor inverse agonist.
Correspondence to clinical effects
Trazodone acts predominantly as a 5-HT 2A receptor antagonist to mediate its therapeutic benefits against anxiety and depression.
The combined actions of 5-HT 2A and 5HT 2C receptor antagonism with serotonin reuptake inhibition only occur at moderate to high doses of trazodone.
Trazodone’s potent α 1 -adrenergic blockade may cause some side effects like orthostatic hypotension and sedation. Conversely, along with 5-HT 2A and H 1 receptor antagonism, it may contribute to its efficacy as a hypnotic. Trazodone lacks any affinity for the muscarinic acetylcholine receptors, so does not produce anticholinergic side effects.
mCPP, a non-selective serotonin receptor modulator and serotonin releasing agent, is the major active metabolite of trazodone and has been suggested to possibly play a role in its therapeutic benefits.
Trazodone is well absorbed after oral administration, with mean peak blood levels obtained at about one hour after ingestion. Absorption is somewhat delayed and enhanced by food. The drug is highly protein-bound. Trazodone is extensively metabolized, with three or four major metabolites having been identified in the human body, particularly mCPP,
As a consequence of the production of mCPP as a metabolite, patients administered trazodone may test positive on EMIT II urine tests for the presence of MDMA (“ecstasy”).
Trazodone is a triazolopyridine derivative and a phenylpiperazine that is chemically related to nefazodone and etoperidone, each of which are derivatives of it.
Trazodone was developed in Italy, in the 1960s, by Angelini Research Laboratories as a second-generation antidepressant.
Society and culture
Generic names
Trazodone is the generic name of the drug and its INN, BAN, and DCF, while trazodone hydrochloride is its USAN, USP, BANM, and JAN.
Brand names
Trazodone has been marketed under a large number of brand names throughout the world.

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