Psychoactive Pet Prescriptions For Pet Behavior Modification
- Everwell Pets
- Aug 18
- 10 min read
Important Considerations for SSRIs, SARIs, Benzodiazepines , & Anti-Depressants
In today’s veterinary world, more and more behavior concerns are being met with a prescription pad instead of a pause-and-reflect moment. Veterinary behaviorists—despite their comforting title—aren’t trainers. They’re veterinarians who diagnose behavioral disorders and prescribe psychoactive drugs, often using the same medications and logic seen in human psychiatry. And just like in human medicine, we need to ask: are we truly healing… or just sedating?
Below we dig into psychoactive pet prescriptions, how they work, and what adverse effects they can bring. We'll also touch on some realities of the drug studies, as well as interesting findings on how the placebo effect impacts human and canine interactions (and outcomes) and round the article off with natural and holistic alternatives to these prescriptions.
FDA Approved Psychoactive Pet Prescriptions
Currently, only three psychoactive drugs are FDA-approved for canine behavior issues:
Fluoxetine (Reconcile) for for separation anxiety
Clomipramine (Clomicalm) for separation anxiety
Dexmedetomidine oromucosal gel (Sileo) for noise phobias.
Off‑Label Prescribing For Dogs
Most vets also prescribe human psychiatric medications off-label—including:
Benzodiazepines: Alprazolam (Xanax), Diazepam (Valium), & Lorazepam (Ativan),
Tricyclic antidepressants: Amitriptyline
SARIs: Trazadone
SSRIs: Fluoxetin (Prozac & Reconcile)
GABA: Gabapentin
Trazodone:
Trazodone is a serotonin antagonist and reuptake inhibitor (SARI) that is commonly prescribed in both human and veterinary medicine. In veterinary use, it's especially popular for managing situational anxiety in dogs.
Trazodone works primarily by inhibiting serotonin reuptake and blocking specific serotonin receptors (5-HT2A). This increases serotonin availability in the brain, promoting calmness and reducing anxiety.
Trazodone works fast and is often used before vet visits, post-op, or during fireworks, thunderstorms or similar noisy environments (see natural calming remedies for noise here).
Adverse Effects: include GI upset, ataxia, and a rare but serious risk of seroton in syndrome when used with other meds [15–16].
SSRIs: Fluoxetin (Prozac & Reconcile)
Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) and one of the most commonly prescribed psychoactive medications for both humans and pets. In veterinary medicine, it is primarily used to treat separation anxiety, compulsive disorders, and aggression in dogs.
Fluoxetine increases serotonin levels in the brain by blocking the reabsorption (reuptake) of serotonin at the synaptic cleft. This enhances serotonergic signaling, which can reduce anxiety, compulsivity, and stress-related behaviors over time.
The FDA-approved veterinary version is Reconcile, which is specifically labeled for the treatment of canine separation anxiety.
In human medicine, fluoxetine is widely known under the brand name Prozac, and it is frequently prescribed off-label by veterinarians for dogs exhibiting behavioral issues such as anxiety, aggression, or obsessive-compulsive disorders.
Adverse Effects: can include vomiting, lethargy, decreased appetite, and in rare cases, increased anxiety or aggression at first [13–14].
Gabapentin:
Gabapentin is a neuro-modulator originally developed to treat seizures in humans, but it is now widely used off-label in veterinary medicine for anxiety, pain management, and fear-based behaviors in dogs and cats despite little evidence.
Gabapentin works by binding to the alpha-2-delta sub-unit of voltage-gated calcium channels in the central nervous system. This reduces the release of excitatory neurotransmitters like glutamate, which helps calm nerve activity. Although it's structurally similar to GABA (gamma-aminobutyric acid), it does not bind to GABA receptors.
Gabapentin is frequently prescribed in veterinary medicine to address a variety of conditions. It is commonly used for situational anxiety, such as during vet visits, car rides, or fireworks, and is also effective for chronic pain, particularly neuropathic pain stemming from conditions like arthritis or intervertebral disc disease (IVDD).
Veterinarians often administer gabapentin alongside other medications, such as trazodone or non-steroidal anti-inflammatory drugs (NSAIDs), to enhance its calming and pain-relieving effects. However, anecdotally, I’ve observed that the combination of trazodone and gabapentin can sometimes have the opposite effect: instead of calming the dog, it leads to increased agitation and restlessness.
Typically, gabapentin is given a few hours before a stressful event due to its short half-life in dogs, which means its effects are temporary but beneficial for acute scenarios.
Adverse Effects: While it is generally well tolerated, potential side effects include sedation, wobbliness or ataxia, hypersalivation (drooling), and, less commonly, gastrointestinal upset. In some dogs—especially when combined with other sedatives—gabapentin can cause profound lethargy. [17–18]
Dexmedetomidine oromucosal gel (Sileo)
Sileo is an FDA-approved alpha-2 adrenergic agonist used in dogs to treat noise aversion (like fear of fireworks, thunderstorms, or other loud sounds).
Dexmedetomidine works by binding to alpha-2 receptors in the central nervous system, inhibiting the release of norepinephrine—a neurotransmitter involved in arousal and the stress response. This results in sedation, anti-anxiety effects, and muscle relaxation, without suppressing respiration like opioids or some anesthetics.
Administered via the oral mucosa (inside the cheek or gums), Sileo is absorbed rapidly through the tissues, offering fast-acting relief typically within 30 to 60 minutes.
Though marketed as easy to use and effective, dexmedetomidine is approved only for noise aversion, though some veterinarians use it off-label for other situational anxieties.
Adervse Effects: include drowsiness or lethargy, vomiting, bradycardia (slow heart rate), hypotension (low blood pressure), and pale gums or mucous membranes. Because of its potency, it’s not recommended for dogs with heart conditions, and repeat dosing should be carefully managed under veterinary guidance.[30]
Benzodiazepines: Alprazolam (Xanax), Diazepam (Valium), & Lorazepam (Ativan)
Benzodiazepines are psychoactive drugs frequently prescribed off-label in veterinary medicine for short-term management of anxiety, noise phobia, or panic behaviors in dogs. Though widely used, their pharmacological footprint is far from benign.
These drugs act on the central nervous system by enhancing the effect of the neurotransmitter GABA (gamma-aminobutyric acid) at the GABA-A receptor. GABA is the brain’s primary inhibitory neurotransmitter—its job is to slow down neural activity.
Benzodiazepines don't create new GABA but increase its calming effect, making neurons less likely to fire. The result? A reduction in anxiety, muscle tension, and in some cases, seizure activity. In dogs, this can manifest as rapid-acting sedation, decreased reactivity to triggers (like thunder or vet visits), and a generally calm demeanor—but at a neurological cost.
Adverse effects: may include lethargy or profound sedation, ataxia (loss of coordination), increased appetite (especially with diazepam), paradoxical excitement (where some dogs become more agitated instead of calmer), dis-inhibition of aggression (dogs may bite or snap when they wouldn't normally), and liver toxicity, especially with long-term diazepam use in sensitive dogs.
Importantly, benzodiazepines do not address the root cause of anxiety. They chemically mute the response but leave the brain in a chemically dependent state—meaning the anxiety is still there, just under sedation.
Additionally, dogs can develop tolerance (needing higher doses for the same effect) and physical dependence over time, especially if benzodiazepines are used daily or long-term. Withdrawal symptoms can be serious and include rebound anxiety (worse than baseline), irritability or aggression, tremors, restlessness, pacing, and in severe cases, seizures—particularly if the drug is stopped abruptly after prolonged use.
These withdrawal effects underscore the need to taper slowly under veterinary supervision. [1–5]
Tricyclic Antidepressants (Clomipramine)
Tricyclic antidepressants work by inhibiting the reuptake of serotonin and norepinephrine in the brain, thereby increasing their levels in the synaptic cleft.
This enhances mood and reduces anxiety-related behaviors. It has a higher affinity for serotonin transporters than norepinephrine, which makes it somewhat similar to SSRIs in action—though it’s classified as a TCA due to its chemical structure. It’s used for anxiety, obsessive behaviors, chronic pain, and even inappropriate urination.
Adverse Effects: Dry mouth, constipation, urinary retention, and heart rate irregularities [11–12].
Limitations Of Drug Studies (or lack of entirely):
Clomipramine and Fluoxetine
Studies suggest clomipramine and fluoxetine reduce compulsive behaviors such as tail chasing in roughly 75% of treated dogs. In one study, nine of twelve dogs showed significant behavioral reduction after 1–12 weeks of clomipramine treatment [19].
Comparative trials found both drugs equally effective in reducing tail chasing, outperforming placebo across multiple time intervals [20].
Notice this is a very small study and could take up to 3 months to notice a reduction in a compulsive behavior.
Similarly, fluoxetine paired with behavior modification improved separation anxiety in about 72% of dogs, compared with 50% in the placebo-and-training group [21].
Despite these findings, many of the behavioral improvements mirrored placebo groups when behavioral training was included, suggesting behavioral change may be driven more by environment than the medication.
Trazodone
Studies indicate trazodone occasionally reduces stress in hospitalized or recovering dogs but failed to show benefits in post-surgical confinement when tested against placebo [22].
I found this pretty surprising—especially since trazodone seems to be handed out like candy to every post-surgical pup as a “calm them down” catch-all.
Gabapentin:
Commonly used before vet visits for anxious dogs, it lacks controlled trials for anxiety relief in dogs; most evidence comes from anecdotal use with sedative side effects in nearly half of recipients [23].
Fluoride in Psychoactive Drugs
You may have come across concerns that fluoride additives in psychoactive drugs may cause sedation beyond the intended active compound. Independent analysts question this, highlighting that over 20% of pharmaceuticals, including common psychiatric drugs like fluoxetine, contain fluorine to enhance stability, metabolic resistance, and bioavailability. These fluoride additives supposedly do not act directly on the brain.[24]
That said, research into chronic, low-level fluoride exposure—particularly environmental or developmental—has raised concerns. Meta-analyses and toxicology reviews have found associations between fluoride exposure and decreased IQ, impaired memory, and emotional symptoms like anxiety or depressed mood in humans, though causality and relevance to adult pharmaceutical dosing remain unclear [25,26].
Animal studies further suggest that prolonged high-dose fluoride exposure can impair hippocampal neuron density and associative memory in rodents—but these doses are far higher than the fluorine content humans or dogs would receive from medications [27].
But this presumption stops short of addressing cumulative exposure, especially if said dog (or human) has been on one, or heck, a cocktail of pharmaceuticals for years, and doesn't consider other sources, like drinking water and hygiene products.
The broader question of fluoride's systemic impact continues to be explored—especially given fluoride’s endocrine disruption and potential neurotoxicity under chronic exposure.
The Placebo Effect: It’s Real
One underappreciated factor in behavior modification is the placebo effect—specifically, the caregiver placebo effect. When pet parents believe a treatment will help, their own behavior often changes: they become more attentive, reinforce calm behaviors, and adjust their energy around the pet. This shift alone can create a measurable change in the dog’s behavior.
A study investigating pulsed electromagnetic field (PEMF) therapy for dogs with separation anxiety found significant improvements in both the treatment and placebo groups. Notably, the placebo group's progress was attributed not to any active intervention but rather to improved owner interaction and engagement throughout the study period [28].
This really drives home the idea that what the human brings to the table—expectation, energy, engagement—can dramatically shift the outcome, even when the dog isn’t actually getting any treatment at all.
The same phenomenon has been observed in studies involving epilepsy, arthritis, and other chronic conditions in dogs, where placebo groups showed noticeable improvements solely through changes in caregiver behavior and perception [29].
Now, don’t get me wrong—medication can work, and in some cases, it’s exactly what’s needed. But it does make you pause and wonder: are we actually calming the dog... or just the human? And if simple, thoughtful engagement can spark such real change, maybe—just maybe—that should be where we start.
A Parallel with Children: Medicalizing Behavior
The prescription of psychoactive drugs to address behavioral issues in dogs parallels what we’ve seen with children in school environments. Over the decades, diagnoses of ADHD, mood disorders, and anxiety in kids drove widespread prescription of medications like Ritalin, Adderall, and SSRIs rather than transforming educational environments to embrace neuro-diversity.
Similarly, dogs now frequently receive medication when their behavior—like barking, energy levels, or separation anxiety—does not conform to modern domestic expectations. Too often, medication becomes the go-to rather than lifestyle adjustments, training, or environmental enrichment.
Holistic Alternatives: Supporting Balance Without Sedation
For many pets, a holistic approach may offer deeper healing than pharmaceuticals alone. Traditional Chinese herbal medicine combined with acupuncture and nutritional support often shows greater success for behavioral issues rooted in imbalance rather than pathology. Herbal blends involving Bupleurum for irritability, Zizyphus seed for restlessness, Poria for cognitive calm, and Licorice to harmonize emotional tone can nurture balance rather than suppress it.
While peer-reviewed animal studies on these herbal formulas are still limited, longstanding clinical traditions and positive anecdotal outcomes provide a strong reason to explore them. Working with a licensed veterinary acupuncturist or Chinese herbalist ensures safety and species-appropriate dosing.
In Conclusion
In our well-meaning mission to help our pets feel safe and emotionally steady, we’ve got to ask the hard question: are we truly supporting their balance and resilience—or just sedating them into compliance? Sure, psychoactive meds can be helpful in true crisis moments, but let’s be real—they’re often nothing more than emotional mufflers, turning down the volume on symptoms without ever getting to the root of why the behavior is happening in the first place. It’s symptom management, not true healing. And those growing questions about fluoride’s role in these meds? They deserve real curiosity, not a quick wave-off. The good news? There’s a whole world of alternatives—thoughtful training, calming herbs, enriched environments, and species-appropriate diets—that actually support long-term healing from the inside out. It’s time they had a louder voice at the table.
If you’re interested in exploring holistic care, behavior modification, or integrative support for your pet’s emotional well-being, consider booking a Pet Wellness Coaching Session with Dr. Andi, or joining the Unleashed Membership for community-based guidance and empowerment. Choose support, not sedation—choose true healing.
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Citations
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Comparative trial showing similar efficacy of clomipramine and fluoxetine (PubMed ID: 22215314).
Fluoxetine + behavior modification improves separation anxiety vs placebo & training (72% vs 50%).
Veterinary evidence review: trazodone reduces stress in hospitalized dogs but not always post-surgical confinement.
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