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The clinical effect of transdermal mirtazapine in healthy young cats

Benson KK, Zajic LB, Quimby JM, et al. Drug exposure and clinical effect of transdermal mirtazapine in healthy young cats: a pilot study. J Feline Med Surg. 2016 Sep 9.

The use of appetite stimulants in feline medicine is a well-established part of the management of both acute and chronic diseases. Appetite stimulation allows for the nutritional support of feline patients until they are able to recover from a disease or as a part of palliative care. Potentially the most commonly used appetite stimulant is mirtazapine, which is generally administered at doses of 1.8mg/cat every 24 hours, or 3.75mg every 3 days. Mirtazapine is an atypical antidepressant with serotonergic and noradrenergic activity. Cats administered mirtazapine often experience increased hunger as well as decreased nausea.

Transdermal (TD) administration of medications has several advantages over traditional routes. The most obvious of these is the cat does not need to be administered a pill, which can minimize stress on the patient and the owner. A major downside to the transdermal administration of medications is that absorption can be erratic and unpredictable, resulting in a varied dose of medication. Not all medications can be absorbed equally well by a transdermal route.

The authors of this study attempted to determine the efficacy of mirtazapine administered by a transdermal route. Doses that were used were based on data from previous, preliminary studies. The study occurred in two phases. The first phase of the study investigated whether the drug exposure of a single dose of 3.75 or 7.5mg transdermal mirtazapine mimicked that of oral administration and how that changed after regular administration.

The second phase was a randomized, double blinded, crossover, placebo controlled trial that investigated the effects of transdermal mirtazapine on client owned cats. These cats had blood sampled to determine mirtazapine levels and also had owners complete questionnaires to determine food intake and behaviour scores. 7 cats were enrolled in the first phase and 20 in the second. Blood levels of mirtazapine were determined by liquid chromatography coupled to mass spectroscopy (LC/MS/MS).

Blood levels of mirtazapine after transdermal administration did not exhibit a typical curve, but reached a steady state for 48 hours after administration and was still detectable after 72h. Multiple doses of 7.5mg reached a higher concentration than single dose oral 1.88mg. There was no significant difference between 3.75mg TD, 75mg TD, and 1.88mg oral mirtazapine.

After administration of 7.5mg TD to client owned cats there was a significant increase in owner reported appetite and food ingestion scores. However, this was also associated with an increase in begging and vocalization, and in two cats with undesirable food seeking.

The authors also investigated the concentration of mirtazapine in compounded transdermal medications. Determination of drug concentration revealed a concentration ranging from 75-116% of the target dose, indicating significant variability (at this level, 7.5mg could actually deliver 5.6mg to 8.7mg). This was determined in phase one of the study, and steps taken to more tightly control drug concentrations for phase 2. However, this does broach the important subject of quality control in compounded medications.

These results indicate that administration of TD mirtazapine at 3.75mg and 7.5mg doses is associated with serum concentrations comparable to oral administration and with significant duration of action. Clinical efficacy at this dose was appreciated in hospitalized and client owned cats.

The authors concluded that transdermal mirtazapine could be a viable option in the management of anorexia in cats, however the dose required is likely much larger than what is generally given orally. A consequence of this higher dose was an increased incidence of agitation and other negative effects. While effects were less intense, they may be acceptable in many conditions Further work is required to determine the ideal dose and frequency in order to stimulate appetite and prevent adverse effects. (MRK)

See Also
Quimby JM, Gustafson DL and Lunn KF. The pharmacokinetics of mirtazapine in cats with chronic kidney disease and in age-matched control cats. J Vet Intern Med 2011; 25:985–989.