Mirtazapine

(for veterinary information only)

BRAND NAME: REMERON

AVAILABLE IN 
15 mg, 30 mg, 45 mg
TABLETS   

BACKGROUND

Mirtazapine was developed for human use as an antidepressant for moderate to severe depression. It is not a tricyclic antidepressant like clomipramine or amitriptyline but is actually a member of the “tetracyclic” class, because it has four chemical rings, rather than three, in its structure. Mirtazapine acts to increase norepinephrine and serotonin in the brain, though there is some question as to how this is actually accomplished. Norepinephrine is a stimulating neurotransmitter and serotonin is a neurotransmitter associated with relaxation and comfort, thus increasing the brain levels of these substances could be very helpful in treating depression.

While there is certainly a call for anti-anxiety medications in veterinary medicine, it is generally its side effects which make mirtazapine such a desirable medication for animals. Mirtazapine has strong anti-nauseal properties by acting on the neuroreceptors in the intestine and stomach that communicate with the vomit center of the brain. It also acts as a strong appetite stimulant. Obviously, a medication that addresses both nausea and appetite loss is boon to the treatment of many medical conditions. Apparently mirtazpine increases central nervous system serotonin but antagonizes serotonin-activity in the gastro-intestinal tract which is how it exerts the effects that we like.

Mirtazapine comes in a regular formula as well as a rapid-dissolving formula. Either may be used in animals.

HOW THIS MEDICATION IS USED

Mirtazapine is used in the treatment of conditions where poor appetite and nausea go together such as in the treatment of intestinal/stomach disease, liver or kidney disease, or any other condition involving both nausea and appetite loss. Mirtazapine can also be used to alleviate the nausea/appetite loss that accompanies the treatment of cancer by chemotherapy.

In the dog, mirtazapine is generally given once a day, a relatively convenient dosing schedule compared to other medications. Even better, in cats mirtazapine is given twice a week.

In the event of liver disease or kidney disease, the clearance of this drug from the body is reduced by approximately 30% so ideally the dose should also be reduced. In cats, it is difficult to reduce the dose as the smallest tablet manufactured cannot be accurately cut much smaller than the regular dosing schedule allows. In this situation, a compounding pharmacy could be employed to create a lower dose or the dosing schedule can be stretched out. This is especially important for cats with liver disease.

Mirtazapine also has antihistamine properties but it is unlikely to be used for these when so many other antihistamines are more readily available.

SIDE EFFECTS

The most common side effect of this medication is drowsiness.

Mirtazapine decreases cortisol secretion by the adrenal glands but has not actually panned out as a treatment for Cushing’s Syndrome, where excess adrenal steroids are produced by the adrenal glands.

Serotonin syndrome is a potential side effect should brain levels of serotonin get too high but this syndrome generally requires a combination of serotonin-increasing medications. Elevated heart rate, tremors/shivering, dilated pupils, difficulty breathing, elevated body temperature, or high blood pressure can all be signs of serotonin syndrome. Animals with serotonin syndrome sometimes demonstrate general hyperactivity. If there is any question that serotonin syndrome is occurring, cyproheptadine can be used as an antidote.

At higher doses, mirtazapine may cause a drop in blood pressure or an elevation in heart rate.

Occasionally, mirtazapine has been reported to cause abnormalities in blood cell lines developing in the bone marrow. If a patient is known to have leukemia, low platelets, or some other blood disease mirtazapine can still be used but extra monitoring tests are probably in order.

INTERACTIONS WITH OTHER DRUGS

Inhibitors of Monoamine Oxidase-A are drugs that cannot be used with miratazpine but MAO-A inhibitors are not used in veterinary medicine so this is of little concern. (The exception would be Amitraz, the active ingredient in the PrevenTIC® tick protection collar and in Mitaban® dip used against demodectic mange. Amitraz is both an MAO-A and MAO-B inhibitor.) The only other MAO inhibitor used in veterinary medicine is seligiline which is an MAO-B inhibitor and a 14 day "wash out" period is recommended between the use of seligiline and mirtazapine.

Use of mirtazapine with selective serotonin reuptake inhibitors ("SSRI's")can raise brain serotonin levels high enough to create "serotonin syndrome" as mentioned above. Mirtazapine should not be used with these drugs. The most commonly used SSRI in veterinary medicine would be fluoxetine (Prozac®).

CONCERNS AND CAUTIONS

Safety of mirtazapine is unproven in pregnancy and lactation.

Patients with liver or kidney disease should receive a reduced dose of mirtazapine or a reduction in the dosing schedule as discussed above. Concurrent use with tramadol can also increase the risk for serotonin syndrome.

Page last updated: 2/6/2013