Serotonin Syndrome in Dogs: Causes, Symptoms, and Treatment

Serotonin syndrome in dogs (dangerously high levels of the brain chemical serotonin) is a potential risk with some medications and supplements. Integrative veterinarian Dr. Julie Buzby explains how serotonin syndrome occurs, the symptoms to watch for, medications and supplements that are more likely to be linked to serotonin syndrome, and what diagnosing and treating it entails.

As a veterinarian and founder of Dr. Buzby’s Senior Dog Co., I receive comments and questions from concerned dog parents frequently. One day, I got the following message:

“I am reaching out to see if Dr. Buzby can help me understand serotonin syndrome and the risk a little better. I started researching every supplement my dog is on, and it turns out that a lot of them increase serotonin—SAMe, ginkgo, even cranberries for urinary tract health. And even chicken, which is the protein in [my dog’s] daily meal, has tryptophan, the precursor to [serotonin]. It’s making me totally paranoid! I don’t know what is risky and what isn’t.”

Wow! I always applaud dog parents for wanting to understand their dog’s health and be a part of the treatment plan, and this diligent dog dad is doing just that. His questions are great, and I think we should explore their answers.

What is serotonin syndrome in dogs?

Serotonin syndrome in dogs is a dangerous condition that occurs when levels of the neurotransmitter (brain signaling chemical) serotonin become too high. It is most likely to happen when the dog is taking or accidentally ingests medications and/or supplements that have the ability to raise serotonin levels.

Serotonin’s specific job is to regulate mood, digestion, sleep, and body temperature. It also helps with pain perception, constriction of blood vessels, and digestive system function. Serotonin is very important for your dog’s normal body functions.

But too much serotonin can become problematic and lead to serotonin syndrome. When there is excessive serotonin in the body, the serotonin receptors become overstimulated. The result is a chain reaction that can be dangerous and life-threatening. Dogs may experience vomiting, diarrhea, restlessness, tremors, seizures, and more.

Before we go too far, I want to mention that serotonin syndrome is rare. However, it is important for dog parents to be able to recognize the symptoms and take action if they see them.

What are the symptoms of serotonin syndrome in dogs?

The clinical signs of serotonin syndrome can vary depending on the dog, how much serotonin is present, and what drug or combination of drugs the dog ingested. Since serotonin is important for normal digestion and brain function, high serotonin levels lead to symptoms of gastrointestinal upset and neuromuscular abnormalities (problems with the brain, nerves, and muscles).

GI symptoms

Some of the gastrointestinal symptoms of serotonin syndrome include:

• Decreased appetite: Your dog might not feel like eating much.
• Vomiting and diarrhea: Digestive upset is common, including vomiting and diarrhea.
• Abdominal pain: Dogs with abdominal pain may stand in a play-bow position or have an arched back.
• Drooling: Dogs with serotonin syndrome produce more saliva (hypersalivate) and, therefore, may drool.

Neurological and behavioral symptoms

Dogs may also develop a variety of symptoms related to their nerves, muscles, or mental status, such as:

• Sedation: Acting sleepy or sedate is often one of the first signs of serotonin syndrome in dogs.
• Muscle tremors or shaking: Your dog might be shivering, twitching, or shaking involuntarily.
• Rigid muscles or stiffness: Stiff posture, firm-feeling muscles, and stiff legs are possible.
• Disorientation or confusion: Because of the effects on the brain, the dog may act puzzled or unsure of his or her surroundings.
• Transient blindness: Dogs may experience sudden and temporary blurring or loss of vision.
• Difficulty walking: You might notice your dog is wobbly and off balance.
• Seizures: Loss of consciousness, paddling, stiffness, and other components of seizures in dogs can occur.
• Restlessness, pacing, agitation, or discomfort: It may seem like your dog can’t settle down.
• Dilated pupils: Both of your dog’s pupils will look larger than normal even in normal light.

Other symptoms

Some additional signs of serotonin syndrome in dogs include:

• Increased or decreased heart rate: When you check your dog’s vital signs, you may notice his or her heart is beating faster than usual. Or alternatively, sometimes it is slower than normal.
• Panting or rapid breathing: Even without exercising and at a comfortable ambient temperature, you might notice your dog breathing fast or panting.
• High temperature: If you check your dog’s temperature, it might be above 103° F.
• High blood pressure: The vet may also detect an elevated blood pressure (hypertension in dogs).

How soon will you see symptoms of serotonin syndrome?

High levels of serotonin can start affecting the nervous system as soon as 30 minutes after taking the medication. Otherwise, the symptoms usually appear within 12 hours of ingesting the drug.

However, in some cases (usually when multiple serotonin-boosting medications are being given together), it can take up to three days for the effects to compound one another and lead to serotonin syndrome.

What should I do if I’m worried my dog has serotonin syndrome?

While serotonin syndrome is rare, it can be a life-threatening condition. If you see symptoms that you think could be related to serotonin syndrome, make an emergency vet visit immediately. Bring a list of all your dog’s medications and supplements, or bring along the bottle of medication the dog got into. This will provide valuable information to the veterinary team.

What causes serotonin syndrome in dogs?

Letting your vet know which medications and supplements your dog is taking or has eaten is important because serotonin syndrome happens in two main ways. One possibility is that the dog ingests too much of a drug or supplement that raises serotonin levels. For example, the dog might get into a bottle of human or dog medications that affect serotonin levels. Or the dog may accidentally receive a significant overdose of his or her medication or be more sensitive to the effects of the medication.

Alternatively, it could be a case where the dog is taking multiple medications and supplements together that all have the ability to increase circulating serotonin. By themselves, each medication doesn’t cause a problem. But when you stack the effects on top of each other, the serotonin levels get too high.

Let’s take a look at some of the more common culprits.

What drugs or supplements cause serotonin syndrome in dogs?

The most common types of medications that increase serotonin are antidepressants, anxiety medications, and pain medications. These types of medications are often serotonergic drugs, which means that they promote or enhance serotonin in the brain. This is helpful because serotonin can help combat feelings of depression and anxiety.

However, excessive amounts of serotonin can cause side effects and serotonin syndrome. Below are some of the classes (or types) of drugs that could contribute to serotonin syndrome, and a few examples of the specific drugs in each class:

1. Selective serotonin reuptake inhibitors (SSRIs)

Selective serotonin reuptake inhibitors (SSRIs) are antidepressants that increase the amount of serotonin in a dog’s (or person’s) brain. They work by blocking the normal reuptake of serotonin into nerve cells, thereby allowing serotonin to remain active in the brain. Some of the more common SSRIs include:

• Fluoxetine for dogs (Prozac®): Fluoxetine is used in both dogs and humans for anxiety.
• Sertraline (Zoloft®): In dogs, vets use it to treat anxiety, aggression, and OCD. Humans commonly take Zoloft, too.
• Citalopram (Celexa®): This medication is not usually used in dogs, but it is an antidepressant that is used in humans. If your dog experiences accidental ingestion of your citalopram pills, it is important to let your veterinarian know.

2. Tricyclic antidepressants

Tricyclic antidepressants are often used to treat depression and anxiety in dogs and humans. Just like SSRIs, they work by blocking serotonin reuptake to increase the amount of serotonin in the brain. They also increase the levels of another neurotransmitter, norepinephrine. This contributes to the anti-anxiety effects. Examples of tricyclic antidepressants include:

• Trazodone for dogs: Veterinarians commonly prescribe trazodone for dogs with anxiety, especially situational or fear-related anxiety (such as fear of thunderstorms, separation anxiety, or anxiety related to going to the vet). But some dogs may take it for long-term anxiety management as well. Trazodone is also prescribed for humans.
• Amitriptyline (Elavil®, Levate®): Sometimes vets prescribe amitriptyline for dogs with anxiety, nerve pain, or itchiness. Plus, it may be effective in cats for managing excessive grooming, inappropriate urination, and other anxiety symptoms. Humans take it for a variety of conditions, too.
• Clomipramine (Clomicalm®): Veterinarians often use clomipramine in combination with other therapies for anxiety in dogs, especially separation anxiety. Plus, it may reduce compulsive behaviors in dogs.
• Mirtazapine: Most commonly, vets use mirtazapine as an appetite stimulant in dogs and to decrease nausea.

3. Monoamine oxidase inhibitors (MAOIs)

Monoamine oxidase inhibitors (MAOIs) work by blocking the enzyme that breaks down serotonin and norepinephrine to increase serotonin levels in the brain.

The most common example is selegiline for dogs (Anipryl® or l-deprenyl). Vets may use it to treat canine cognitive dysfunction. Also, it is sometimes useful for Cushing’s disease in dogs. Humans take selegiline to manage Parkinson’s disease and depression.

4. Miscellaneous medications

SSRIs, TCAs, and MAOIs are the biggest contributors to serotonin syndrome. But other miscellaneous drugs could also lead to the condition, including:

• Some human ADHD medications cause extra release of serotonin. These can lead to serotonin syndrome in dogs if accidentally ingested.
• Tramadol for dogs, a pain medication for dogs, cats, and humans, can affect serotonin levels.
• Human medications, such as cough suppressants, may contain dextromethorphan. It has been linked to serotonin syndrome in dogs.
• Ondansetron is an anti-nausea medication which is used in both dogs and humans. It can influence the serotonin pathway when overdosed or used in combination with other drugs.
• Metoclopramide (Reglan® or Maxolon®), a medication used for nausea, vomiting, and acid reflux in dogs, may contribute to serotonin syndrome. Humans also take it for digestive problems.
• Illicit drugs like methamphetamine, cocaine, or LSD can also cause serotonin syndrome.

6. Supplements

There are some supplements that, when given in too large a dose or in combination with serotonin-affecting medications, can cause adverse effects like serotonin syndrome.

• Melatonin: Melatonin for dogs has many uses, from resetting sleep-wake cycles in dogs with dementia to managing hair loss. However, serotonin is a precursor to melatonin, and some melatonin supplements are contaminated with serotonin. Thus, there is a risk that combining a melatonin supplement with another drug that increases serotonin (like selegiline, a common medication for dogs with dementia) could increase the risk for serotonin syndrome.
• St. John’s Wort: People may take the herbal medication St. John’s Wort for depression and some skin problems. It can be toxic for dogs and lead to serotonin syndrome.
• L-tryptophan or 5-HTP: Tryptophan is in turkey, but dogs will not get serotonin syndrome from eating a piece of turkey or from eating dog kibble that has turkey as the main protein source. However, L-tryptophan or 5-HTP (which is produced from tryptophan on the pathway to making serotonin) is sometimes used as a calming or anti-anxiety supplement, especially in people. Tryptophan and 5-HTP are serotonin precursors. If your dog accidentally eats some of the supplement, it could lead to serotonin syndrome. 

Be aware of medications that cause serotonin syndrome

The information above is not comprehensive because the list of possible drugs and supplements implicated in serotonin syndrome is long. However, it does include some of the most common medications and supplements to be aware of.

It is important to immediately let your veterinarian know if your dog accidentally gets an overdose of his or her prescription or if your dog accidentally consumes your medication. You can also call ASPCA Animal Poison Control Center or Pet Poison Helpline for advice if your dog gets into a medication (a consultation fee may apply).

This is a great example of one of the reasons why you should always give your veterinarian a complete list of all your dog’s current medications and supplements—especially before starting (or stopping) a new prescription. Ensuring your veterinarian is aware of everything your dog is taking can help avoid drug interactions and complications like serotonin syndrome.

Can gabapentin cause serotonin syndrome in dogs?

The good news is that gabapentin, another medication that veterinarians commonly use to manage anxiety and pain in dogs, does not cause serotonin syndrome. Gabapentin for dogs works by binding to calcium channels to affect signals in the brain rather than increasing serotonin levels like the other medications discussed above.

How do vets diagnose serotonin syndrome in dogs?

There is no exact test for serotonin syndrome. Instead, your veterinarian will diagnose the condition based on exposure to serotonin-affecting drugs or supplements, your dog’s symptoms and physical exam findings, and the exclusion of other possible diseases.

History of exposure to medications that affect serotonin

During the appointment, your veterinarian will ask you about your dog’s symptoms and discuss what medications and supplements your dog is taking or could have been exposed to. Having a list of the medications (or the bottles) is very helpful.

Symptoms and physical exam findings that fit serotonin syndrome

As part of the physical exam, your veterinarian will look for signs of gastrointestinal upset or pain, changes in mental status, and muscular or neurological abnormalities. Plus, he or she will check your dog’s vitals like heart rate, temperature, and blood pressure. As discussed earlier, serotonin syndrome can affect all those body systems.

Ruling out other conditions with similar signs

Your veterinarian may run blood tests for dogs to look for signs of toxicities, electrolyte imbalances, or other problems that could cause similar symptoms. He or she may also recommend various tests to ensure that the signs aren’t related to an underlying neurologic issue in dogs. (There are also tests a diagnostic lab can run on urine, blood, or stomach contents to detect serotonin, but they take a while to get back, so they aren’t helpful in an emergency situation.)

Note: Because serotonin syndrome can progress quickly and become life-threatening, there isn’t always time to wait for diagnostic tests to rule out other diseases. If your veterinarian suspects serotonin syndrome based on the history, symptoms, and physical exam, he or she may recommend starting treatment immediately. This often means the diagnostic tests get completed while concurrently treating the dog for serotonin syndrome.

What is the treatment for serotonin syndrome in dogs?

Your veterinarian will develop a treatment plan based on the severity of the serotonin syndrome.

Treatment for mild cases of serotonin syndrome

If a dog has a mild case of serotonin syndrome and the symptoms have just started, the veterinarian might recommend reducing the dose of the serotonin-influencing medication or stopping the medication. Then, he or she, plus the dog parent, should monitor the dog carefully for worsening symptoms. If the dog improves with the change in the medication, he or she may not need further treatment for serotonin syndrome.

But, if your dog has a moderate or severe case of serotonin syndrome, he or she will require more extensive supportive care.

Treatment for moderate or severe cases of serotonin syndrome

For more severe cases, it is still important not to continue giving the dog the problematic medication or supplement. Additionally, the vet will usually hospitalize the dog so he or she can continuously monitor vitals like heart rate, blood pressure, and body temperature. The veterinary team will also watch for changes in behavior and neurological signs.

Preventing further absorption of the medication

The next step is to help get the drugs out of your dog’s body to prevent ongoing effects. If your dog ingested the medication in the last two hours, your veterinarian may induce vomiting. (Do not attempt to make your dog vomit at home unless instructed to do so by the vet. It may not be safe to make a more severely affected dog vomit.)

If it has been longer than about two hours or your dog is already vomiting, the vet may administer activated charcoal to bind to the drug. This can help prevent it from being absorbed and decrease or stop its ongoing effects. (The vet may also use activated charcoal after inducing vomiting.)

Additionally, the vet will often use IV fluids to help support the heart and kidneys.

In some cases, a medication called cyproheptadine for dogs may be used to combat serotonin syndrome symptoms. Cyproheptadine works by reducing the level of serotonin in the brain. The lower levels of serotonin allow symptoms to improve and help a dog recover.

Additional supportive care

Depending on their symptoms, dogs may also receive the following treatments:

• If your dog has an elevated temperature, your veterinarian may use IV fluids, cooling blankets, and fans to lower it.
• Anti-nausea medications like Cerenia for dogs or antacids like omeprazole for dogs can be helpful for dogs who have ongoing vomiting or abdominal pain.
• Dogs who are experiencing neurological changes may need sedatives or muscle relaxers (that don’t affect serotonin levels) to help reduce anxiety, shaking, and muscle tensing.
• The vet may use antiseizure medications to help control seizures.

How long does serotonin syndrome last in dogs?

Most cases of serotonin syndrome (even mild ones) last for a minimum of 24 hours. But many dogs will experience symptoms for two to three days.

What is the prognosis for dogs with serotonin syndrome?

The prognosis for serotonin syndrome depends on the dog’s symptoms and the severity of the condition.

If symptoms are mild and treatment begins quickly, the prognosis is usually good. With appropriate supportive care, many dogs can recover in a couple of days.

But if treatment is delayed and/or symptoms are severe, the prognosis can be guarded, and the condition may occasionally be fatal.

Therefore, being aware of the risks of serotonin syndrome with certain medications, recognizing symptoms immediately, alerting your veterinarian, and seeking quick treatment are imperative to helping your dog have the best prognosis and recovery.

Be aware of, not scared of, serotonin syndrome in dogs

Serotonin syndrome is rare in dogs. But it is important to be aware that it exists because it can also be very serious. This isn’t to say that you should be scared of giving your dog the medications that influence serotonin, though. They can do a lot of good for a lot of dogs (and people). So, the key is really just to be armed with information and diligent about monitoring your dog’s health, both of which you are probably doing anyway.

To help with that mission, keep the following five tips in mind:

1. Secure all human and pet medications, not just the ones that can cause serotonin syndrome, out of reach of your dog.
2. Provide your vet with a list of all medications and supplements your dog is taking so that he or she can take steps to avoid combining serotonin-increasing medications. Also, consult your vet before giving your dog a new supplement.
3. Know the possible side effects of the medications your dog takes.
4. Be aware of the signs of serotonin syndrome so you can recognize it.
5. Get your dog to the vet right away if you do see symptoms of serotonin syndrome.

A reply to a conscientious dog dad

Let’s go back to the dog dad’s letter and his questions that were the inspiration for this blog. I was so impressed with his devotion, research, and forethought regarding serotonin syndrome and the risk factors in his dog’s life. My reply was this:

“Serotonin syndrome is pretty rare in veterinary medicine. I have personally never seen it in 28 years of practice. But I’ve heard stories from colleagues about it and never want to see it! Great job on your research, but I think the risk is low with supplements like ginkgo, SAMe, phosphatidylserine, cranberries, chicken, etc. For me, in all things veterinary medicine, it’s assessing if the potential benefits outweigh the risks. And I think in this prior list, they do, and I would continue them. Thank you again for your lovely email and support of our family-owned small business. Your dog is lucky to have such a conscientious dad.”

I could say the same for you, too. Your dog is lucky to have a dedicated dog parent like you who wants to learn how to help and support him or her in all things.