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These combinations are not usually physically harmful, but may produce undesirable effects, such as physical discomfort or overstimulation. Extreme use may cause physical health issues. Synergistic effects may be unpredictable. Care should be taken when choosing to use this combination.
Trazodone is not associated with abuse potential or recreational use. No reports of compulsive use patterns or psychological dependence have been documented.
Trazodone shares properties with SSRIs including the possibility of discontinuation syndrome if stopped too quickly. Gradual tapering is recommended when discontinuing treatment.
Trazodone appears to be relatively safer than tricyclic antidepressants, MAOIs, and some other second-generation antidepressants in overdose situations. Fatalities are rare, with uneventful recoveries reported after ingestion of doses as high as 6,000-9,200 mg. In one report, 9 of 294 overdose cases were fatal, and all nine patients had also taken other CNS depressants. Taking more than 600 mg within 24 hours substantially increases overdose risk.
| Species | Route | Value |
|---|---|---|
| rat | oral | 690 mg/kg |
QT prolongation and cardiac arrhythmias have been reported with trazodone therapy, including in patients without pre-existing cardiac disease; identified arrhythmias include isolated PVCs, ventricular couplets, and short episodes of ventricular tachycardia.
Rare cases of liver toxicity have been observed, possibly due to the formation of reactive metabolites.
Priapism is a relatively rare but serious side effect that can cause permanent neurological damage if left untreated; the risk appears greatest during the first month of treatment at low dosages.
Memory, alertness, and cognition may be decreased, especially in elderly patients due to CNS depressant effects; sedation commonly occurs and may impair ability to operate machinery or drive.
Trazodone is associated with an increased risk of falls and hip fractures in older adults, likely related to sedation and orthostatic hypotension.
Elevated prolactin concentrations have been observed in people taking trazodone, appearing to increase by approximately 1.5- to 2-fold.
The unmasking of bipolar disorder and mania may occur with trazodone and other antidepressants. No specific psychotic symptoms documented beyond manic episodes.
Trazodone is classified as an agent that reduces seizure threshold. Patients with seizure disorders or risk factors should be monitored.
Trazodone was developed in Italy during the 1960s by Angelini Research Laboratories as a second-generation antidepressant. Its development was guided by the mental pain hypothesis, a theory derived from clinical observations proposing that major depression is associated with a decreased pain…
Available as both brand name and generic prescription products. Regulated as a prescription medication under federal pharmaceutical law. Not classified as a controlled substance.
Granted FDA approval in 1981 for the treatment of major depressive disorder. Trazodone is not a scheduled controlled substance under the Controlled Substances Act; it is regulated as a prescription-only medication requiring a valid prescription from a licensed healthcare provider.
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