Treatment of trazodone overdose generally
consists of symptomatic and supportive
care. Although adverse effects are often
reported, relatively few cases have involved
serious signs and no deaths are attributed to
trazodone exposure to date.
9
Special attention
should be given to ensuring maintenance
of cardiac output and being attentive to
signs of hyperthermia or hypothermia and
correcting as needed.
9,11
IV fluid therapy may
be needed to maintain blood pressure.
6,9
Diazepam is the drug of choice for managing
tremors or seizures, and atropine is
suggested for treatment of bradycardia.
6,9
Being aware of signs associated with
serotonin syndrome is important as this can
be a serious and potentially life-threatening
condition to manage. Serotonin syndrome
develops as a result of an overabundance of
serotonin in the central nervous system.
6
It can
be a risk in cases of exposure to high doses
of trazodone.
1,4
Clinical signs of serotonin
syndrome in dogs, in order of most to least
common, include vomiting, diarrhea, seizures,
hyperthermia, hyperesthesia, depression,
mydriasis, vocalization, death, blindness,
hypersalivation, dyspnea, ataxia/paresis,
disorientation, hyperreflexia, and coma.
1
Cyproheptadine, a serotonin antagonist,
helps combat serotonin syndrome signs.
6,11
Phenothiazines should be used cautiously
because of potential hypotensive effects.
6
Interaction With Other Drugs
Trazodone interacts with numerous drugs,
and some of these interactions may have
clinically significant effects. Of special
interest are medications that may be
strong inhibitors or inducers of cytochrome
P450 3A4 (CYP3A4) isoenzyme, which is
involved in trazodone metabolism.
4
Azole
antifungals (eg, ketoconazole, itraconazole,
fluconazole) and macrolide antibiotics (eg,
erythromycin, telithromycin, clarithromycin)
are CYP3A4 inhibitors and thus may enhance
the effect of trazodone.
1,4
Carbamazepine,
phenobarbital, phenytoin, rifampicin, and
modafinil, which are CYP3A4 inducers, may
decrease the effect of trazodone.
1,4,9
Extreme caution should be used with
concomitant trazodone and fluoxetine use and/
or exposure as it is believed that fluoxetine
may inhibit metabolism of trazodone.
1,4
Additionally, fluoxetine and other serotonergic
medications (eg, paroxetine, sertraline,
amitriptyline, clomipramine, amphetamines,
dextromethorphan) as well as monoamine
oxidase inhibitors (eg, phenelzine, amitraz,
selegiline), metoclopramide, and tramadol,
could heighten the risk of serotonin syndrome
when combined with trazodone.
1,4,6,8
Serotonin syndrome patients with severe
cardiac disease or renal and/or hepatic function
deficits should be monitored very closely and
may merit additional treatment measures.
1
Prognosis
The prognosis for patients exposed to
trazodone is generally good, especially when
serotonin syndrome has not developed.
Signs generally resolve in 12 to 24 hours.
6
Trazodone in Veterinary Medicine
TABLE 1 Signs Associated With
Trazodone Exposure in Dogs
10
SIGN LOWEST DOSE (MG/KG)
AT WHICH SIGN
WAS SEEN
Lethargy 0.55
Depression/vomiting 1.35
Ataxia 1.7
Diarrhea 2.82
Hyperactivity 3.8
Hypotension 5.94
Hyperesthesia 6.06
Vocalization 6.6
Tremors 8.17
Disorientation 8.28
Tachycardia/hypertension 8.83
Hyperthermia 11.8
Collapse 12.99
Mydriasis/bradycardia 16.23
Seizure 78.7
