Is Mirtazapine safe for dogs and cats?

Mirtazapine is used off-label in veterinary medicine for canine anorexia, nausea, and weight loss (particularly in cancer, kidney disease, and GI disease); its appetite-stimulating and antiemetic properties are highly valued in clinical veterinary practice. Veterinary dosing (dogs): 1.88 mg/kg every 24 hours; alternatively 3.75–15 mg per dog depending on size. Serotonin syndrome risk: mirtazapine's 5-HT2 antagonism actually provides some protection against serotonin syndrome — it is unlikely to cause classic serotonin syndrome even at higher doses; this distinguishes it from SSRIs/SNRIs in the toxicity landscape. Toxicity at high doses: large overdoses cause pronounced CNS depression (sedation, ataxia), vocalization, tachycardia, and hyperthermia in dogs — not classic serotonin syndrome but a distinct sedative-hyperstimulatory toxidrome. Interaction with MAOIs: dogs on selegiline (Anipryl for canine cognitive dysfunction) should not receive mirtazapine — MAOI + NaSSA can cause serotonin-like syndrome. Concurrent SSRIs: mirtazapine is occasionally used with SSRIs in veterinary medicine; this combination increases serotonin release (via alpha-2 block) while SSRIs inhibit reuptake — potential for enhanced serotonergic effects. Treatment: supportive; benzodiazepines for CNS excitation; thermoregulation; generally favorable prognosis.

Mirtazapine is the most widely used appetite stimulant in cats and has FDA veterinary approval (Mirataz®, 2 mg/g transdermal ointment) for management of weight loss in cats — one of the few transdermal veterinary psychiatric drugs with an FDA approval. This is a therapeutic-use context, not primarily a toxicity concern. Mirataz dosing: 2 mg (1.5 inch ribbon of ointment) applied to inner pinna (ear) every 48 hours; the transdermal route is chosen because cats are notoriously difficult to medicate orally. Pharmacokinetics in cats: mirtazapine has a much longer half-life in cats (~40 hours) than in humans (~20–40 hours) or dogs (~15–20 hours); every-48-hour dosing reflects this; daily dosing would cause accumulation and overdose. Oral overdose (accidental): cats accidentally ingesting mirtazapine tablets can develop vocalization, agitation, hypersalivation, tremors, ataxia, and tachycardia — at doses exceeding the therapeutic window; treatment is supportive. Paradoxical sedation: therapeutic doses cause appetite stimulation with mild sedation; overdoses can paradoxically cause marked agitation and vocalization before CNS depression. Owner awareness: cat owners prescribed Mirataz must understand that application to both ears or more frequent dosing doubles the dose — dose-related toxicity is the most common clinical problem in feline mirtazapine therapy. Cancer/CKD cats: mirtazapine is particularly valuable in cats with cancer-related anorexia or chronic kidney disease (CKD)-associated appetite loss; improved nutritional status significantly impacts quality of life and survival.