Assessment of compounded transdermal mirtazapine as an appetite stimulant in cats with chronic kidney disease

Abstract

Objectives: The aim of this study was to assess the appetite stimulation properties of compounded transdermal mirtazapine (CTM) in cats with chronic kidney disease (CKD).

Methods: Two sequential double-blind placebo-controlled crossover prospective studies were performed in client-owned cats with stable stage 2 or 3 CKD and a history of decreased appetite. In the first study nine CKD cats were randomized to receive 3.75 mg/0.1 ml CTM gel or placebo on the inner pinna every other day for 3 weeks, then, after a 4 day washout period, the cats were crossed over to the alternate 3 week treatment. In a second study, 10 CKD cats were randomized to receive 1.88 mg/0.1 ml CTM or placebo on the same schedule. Physical examination and serum biochemistry were performed before and after each treatment period, and owners kept daily logs of appetite, activity and eating behaviors. Mirtazapine concentrations in CTM gels and steady-state mirtazapine serum concentrations were measured using liquid chromatography/tandem mass spectrometry.

Results: Administration of both 3.75 mg and 1.88 mg CTM resulted in a statistically significant increase in weight (P = 0.002 for both), increase in appetite (P = 0.01 and P = 0.005, respectively), and increase in rate of food consumption (P = 0.03 and P = 0.008, respectively). No significant difference in activity or vocalization was seen at either dose; however, individual cats experienced excessive meowing. Median weight increase for the 3.75 mg arm was 0.22 kg (range 0.04-0.44 kg), while median weight increase for the 1.88 mg arm was 0.26 kg (range -0.25 to 0.5 kg). Improvement in body condition score was seen in 5/9 cats in the 3.75 mg arm (P = 0.04) and 6/10 cats in the 1.88 mg arm (P = 0.004).

Conclusions and relevance: CTM increased appetite and resulted in weight gain in CKD cats despite significant inconsistencies in compounding, and may benefit cats in countries where an approved product is not available.

Keywords: Renal; compounding; gel; weight.

Figure 1

Consort diagram for 3.75 mg compounded transdermal mirtazapine clinical trial

Figure 2

Consort diagram for 1.88 mg compounded transdermal mirtazapine clinical trial

Figure 3

Change in weight after administration of 1.88 mg compounded transdermal mirtazapine or placebo every other day for 3 weeks. A statistically significant increase in weight was seen (P = 0.002)

Figure 4

Appetite score based on daily owner assessment after administration of 1.88 mg compounded transdermal mirtazapine or placebo every other day for 3 weeks. A statistically significant increase in appetite score was seen (P = 0.005)

Figure 5

Rate of ingestion score based on daily owner assessment after administration of 1.88 mg compounded transdermal mirtazapine or placebo every other day for 3 weeks. A statistically significant increase in rate of ingestion was seen (P = 0.008)

Figure 6

Begging score based on daily owner assessment after administration of 1.88 mg compounded transdermal mirtazapine or placebo every other day for 3 weeks. A statistically significant increase in begging was seen (P = 0.003)

Figure 7

Vocalization score based on daily owner assessment after administration of 1.88 mg compounded transdermal mirtazapine or placebo every other day for 3 weeks. Although no statistically significant difference in vocalization was seen (P = 0.08), individual cats had excessive vocalization as reported by owners