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Effect of High Doses of Fluoxetine in Hyperactive Dogs

Meghan E. Herron, DVM, DACVB, Gigi’s Shelter for Dogs, Canal Winchester, Ohio


|March 2022

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In the literature

Bleuer-Elsner S, Muller G, Beata C, Zamansky A, Marlois N. Effect of fluoxetine at a dosage of 2-4 mg/kg daily in dogs exhibiting hypersensitivity-hyperactivity syndrome, a retrospective study. J Vet Behav. 2021;44:25-31.


Fluoxetine (1-2 mg/kg PO every 24 hours) is FDA-approved for treatment of separation anxiety in dogs; doses >2 mg/kg PO every 24 hours are uncommon, likely due to concern for adverse effects at higher doses and lack of supportive published evidence. 

This study describes extra-label use of fluoxetine to treat hypersensitivity-hyperactivity (HSHA) syndrome, which is characterized by hypermotricity (eg, compulsive exploration of a room, difficulty lying down and resting), difficulty sleeping, and lack of satiety.1 Clinical signs of HSHA are similar to attention-deficit/hyperactivity disorder in humans. 

This study includes the first published data on treatment of HSHA with fluoxetine and is the first to suggest that doses of 2 to 4 mg/kg PO every 24 hours can be well tolerated. Although 88 out of 89 dogs showed improvement in clinical signs, ≈46.1% also experienced adverse effects (ie, lack of appetite, fatigability, sedation, tremors, weight loss), and 10.1% were highly or severely affected. Decreased appetite was significantly correlated with satiety improvement, suggesting lack of appetite might have been considered a positive effect. 

This study was limited by its retrospective nature, as true efficacy compared with placebo (as might be demonstrated in a randomized, double-blinded, placebo-controlled study) could not be confirmed; however, it brings attention to a syndrome not often described in the United States and encourages reconsideration of the traditional fluoxetine dose (ie, 1-2 mg/kg PO every 24 hours). 


Key pearls to put into practice:


In the absence of physical disease, diagnosis of HSHA syndrome should be considered in dogs presented with hyperactive behaviors, interrupted sleep patterns, and insatiable appetites.


Fluoxetine administered above the traditional dose may be considered, but pet owners should understand this is extra-label and adverse effects are possible. Monitoring for adverse effects and subsequently adjusting the dose are key to maximizing the benefits of the higher dose range.


In dogs with HSHA syndrome currently receiving and tolerating fluoxetine at <2 mg/kg PO every 24 hours, increasing to 2 to 4 mg/kg PO every 24 hours may result in greater clinical improvement.



Decreased appetite may be a beneficial response in dogs that lack satiety control and should be considered when selecting selective serotonin reuptake inhibitors.


For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

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