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Dear Davis February

I’m fairly new to using trazodone to calm excitable dogs prior to office visits. If a dog is coming in for surgery and is given trazodone is there any problem with having induction with a mixture of ketamine with a slight touch of acepromazine in it and then going on isoflurane and an NSAID and morphine for pain management? Are there any drugs to use with caution or avoid in combination with trazodone? 

Answer:

Trazodone is fantastic and I hope you have good success and experiences! Yes, I would feel comfortable using all the drugs you listed in combination with trazodone.

Other thoughts:

Acepromazine is a phenothiazine tranquilizer that antagonizes dopaminergic receptors, resulting in the desired goal of sedation. However, acepromazine antagonizes other receptors, including α1-adrenergic receptors, leading to the undesirable effects of vasodilation (hypotension). Technically, trazodone is also an α1-adrenergic antagonist, however, NO published data has concluded any synergism with these two drugs in combination (they do NOT induce a more significant hypotensive experience than acepromazine alone). Some people theorize this is possible, but again, not proven! So, YES, you can use trazodone and ace in combination! MANY anesthesiologists do this and proven to be used together in published reports. Just be sure to monitor blood pressure during the anesthetic event and treat as necessary, like any other anesthesia!

Are there any drugs to use with CAUTION with trazodone? YES:

1-Ketoconazole is an antifungal drug that also inhibits cytochrome P450 3A (CYP3A) metabolism of multiple drugs, including trazodone. By inhibiting this enzyme pathway, there is potential to increase trazodone plasma concentrations, which could result in serotonin syndrome. Therefore, CYP3A-inhibitor drugs should be used with caution in dogs receiving trazodone. Other CYP3A inhibitors commonly used in dogs include erythromycin, clarithromycin, and itraconazole.

2-Mirtazapine is primarily used as an appetite stimulant and antiemetic. It is important to recognize that mirtazapine antagonizes several receptors, including serotonin receptor subtypes, with resultant increased serotonin levels. Because of the risk for serotonin syndrome, mirtazapine should be used with caution in dogs receiving trazodone.

3-Hydroxyzine, an antihistamine used for the treatment of allergies, is an antagonist of serotonin (5-hydroxytryptamine [5-HT]) receptors, specifically 5-HT2A. Because it may increase the risk for serotonin syndrome, hydroxyzine should be used with caution in dogs receiving trazodone.

4-Amitriptyline is a tricyclic antidepressant and therefore should be used with caution in dogs receiving trazodone, as amitriptyline can increase serotonin concentrations, resulting in serotonin syndrome.

5-Tramadol inhibits the reuptake of serotonin and norepinephrine. Therefore, use of tramadol in dogs receiving trazodone could lead to increased concentrations of serotonin and resultant serotonin syndrome. (Many reports exist of trazodone and tramadol used in combination with NO side effects!) *These drugs can be used, just advise to monitor for serotonin syndrome, particularly if used for a long duration or high doses.

Is there anything contraindicated to use with trazodone? YES:

Monoamine oxidase inhibitors (MAOIs; amitraz, isocarboxazid, phenelzine, selegiline, tranylcypromine) are antidepressants primarily prescribed for humans; they are infrequently used in dogs, but of the MAOIs that are used, selegiline is the most common. The main function of monoamine oxidase is to break down dopamine, norepinephrine, and serotonin. MAOIs work by blocking these enzymes, causing an increase in serotonin concentration and other neurotransmitters in the brain. Although MAOIs are not commonly used in dogs, it is important to know that concurrent use of trazodone and MAOIs is contraindicated because of the resultant increase in serotonin concentration and risk for serotonin syndrome.

Signs of serotonin syndrome include confusion, agitation, hyperthermia, tachycardia, seizures, ataxia, tremors, myoclonus, coma, diarrhea, vomiting, inappetence, and hyper- or hypotension. *This is RARE in dogs! Only a few case reports exist. (Vomiting and diarrhea alone would NOT worry me, it is a side effect of trazodone in high doses)..

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