Effect of High Doses of Fluoxetine in Hyperactive Dogs

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.

The Research …

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).

… The Takeaways

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.