Reviewed by Sara Ochoa, DVM
October 30, 2022
Is your dog on an antidepressant? If so, you may have heard about the risks of serotonin syndrome in dogs.
It’s not unusual for dogs with separation anxiety, compulsive disorders or behavioral issues to be prescribed antidepressant medication.
Although antidepressants were originally prescribed to people, veterinary medicine has been using them to treat various conditions in dogs.
Unfortunately, these psychiatric medications can sometimes pose the same risks to animals as they do to people. One of these risks is serotonin syndrome.
Did you know that there are proactive things you can do to reduce the risk of Serotonin Syndrome in dogs?
Serotonin syndrome in dogs usually happens through the accidental ingestion of human prescription medications. Unfortunately, dogs are more susceptible than other species to developing serotonin syndrome.
The good news is that there are ways to ensure your dog’s safety. One of those things (which you are doing right now) is to research and understand the risks.
There are many other things besides medications that can trigger serotonin syndrome. If this is a concern to you, be sure to read the entire post.
What You Should Know About Serotonin
Serotonin (also known as 5-hydoxytryptamine or 5-HT) is a naturally occurring substance that acts as a neurotransmitter.
This neurotransmitter sends signals between nerve cells (or neurons) throughout the body.
Serotonin is made from the essential amino acid known as tryptophan. In order for it to work, the amino acids first have to enter the digestive system through commonly found foods. Examples include nuts, cheeses, and red meat.
When the body is low in serotonin (sometimes due to tryptophan deficiency) it can lead to depression and anxiety. Serotonin is found through the body via the central nervous system but is also found in the peripheral nervous system.
Serotonin in the Central Nervous System
The beneficial effects of serotonin include the regulation of mood, appetite, body temperature, and sleep. It’s also responsible for memory and learning.
While serotonin acts as a neurotransmitter for the central nervous system, it also works as a vasoconstrictor in the blood.
In addition, serotonin promotes healing and can also control the release of insulin-like growth factors.
Serotonin in the Peripheral Nervous System
The peripheral nervous system is simply the nervous system that operates outside of the brain and spinal cord. The central nervous system and the peripheral nervous system work together between the brain and the body.
Serotonin has many diverse effects on the body and is important for overall health in pets and people. Of the approximately 40 million brain cells, most are influenced either directly or indirectly by serotonin.
The diverse effects of serotonin include:
Vasoconstriction refers to the constriction of blood vessels.
Narrowing of the airways in the lungs.
Peristalsis is a series of wave-like muscle contractions that move food through the gastrointestinal tract.
Altered platelet aggregation
Platelet aggregation is a crucial step in the process of clot formation.
What Causes Serotonin Syndrome in Dog?
Serotonin syndrome in dogs occurs when serotonin levels are dangerously elevated in the body. The excess stimulation of serotonergic receptors in the nervous system leads to a serious break-down of normal functioning.
When there is too much serotonin in the brain, it begins to over-fire, sending too many signals for the body to manage.
The simplest way to describe what happens is similar to when a person drinks too much caffeine. A little caffeine might produce a beneficial effect of feeling awake and energetic.
Too much caffeine can leave you feeling jittery and nervous. You might get a headache or even heart palpitations.
When there is too much serotonin (5-HT) in the brain, the body goes into overdrive.
Agents that Increase the Level of Serotonin in the Brain
- serotonin-specific reuptake inhibitors (antidepressants like fluoxetine)
- serotonin-norepinephrine reuptake inhibitors (including venlafaxine and duloxetine)
- tricyclic antidepressants including clomipramine and amitriptyline
- monoamine oxidase inhibitors
- medications like buspirone
Serotonin Precursors (including dietary supplements) that Can Push Therapeutic doses to Toxic Levels
- 5-hydroxytryptophan (5-HTP)
- S-adenosylmethionine (SAMe)
- St. John’s Wort
- Garcinia extract
- Garcinia Cambogia
Foods high in the amino acid tryptophan include:
- Soy products
Signs of Serotonin Syndrome in Dogs
Severe clinical signs of toxicosis can develop within a few hours after taking a serotonin precursor (a serotonin-enhancing drug, food, or supplement).
In dogs (depending on the dog’s body weight and other factors) toxicosis happens quickly. Reports of serotonin toxicity in dogs have been made as quickly as 10 minutes from consumption to four hours later.
Symptoms of Serotonin Syndrome Include:
Unfortunately, symptoms of mild serotonin syndrome are much harder to diagnose.
Signs of severe serotonin syndrome include a combination of the following:
- Mood & behavior changes
- Muscle tremors
- Muscle rigidity
- Hyperthermia (due to high fever)
- Tachycardia (high heart rate)
- Systemic hypertension (high blood pressure).
We’ve talked about serotonin and serotonin syndrome, but we haven’t addressed the importance of antidepressants for some veterinary patients.
Antidepressants can play an important role in the health of our animals. The clinical effects of these medications can help to reduce anxiety in dogs. They can also reduce behavioral issues when combined with behavioral modification therapy.
Next, we’ll discuss antidepressants including the different types and how they work on the body.
DON’T FORGET: Check out the important follow-up posts listed below!
Some of the first-generation antidepressant drugs have the worst side-effects.
In fact, it’s these first generation drugs that increase the risk of serotonin syndrome. For that reason, it’s often the 2nd generation antidepressants that are prescribed these days. They tend to have fewer side-effects.
This video by Dr. Tracey Marks really explains serotonin syndrome in a way everybody can understand:
Common Serotonergic Drugs – First and Second Generation Antidepressant Medication
Serotonergic drugs are those that increase the levels of serotonin in the body. These drugs all have slight differences in the way this is accomplished. Tricyclics and monoamine oxidase inhibitors (or serotonin metabolism inhibitors) are considered first generation antidepressants.
Second generation antidepressants include selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs).
Tricyclics antidepressants (or cyclic antidepressants) were one of the first anti-depressants to treat psychiatric disorders. They came on the market beginning in 1954. They were named tricyclics because of their central three-ring structure.
In veterinary medicine, tricyclics (TCAs) have been shown to have good anti-anxiety effects. They are also used to reduce compulsions and aggression in dogs. As with many anti-depressants, TCAs can take several weeks to reach full effect.
How Tricyclic Antidepressants Work
Tricyclics act as inhibitors of serotonin and norepinephrine. They have both antihistaminic and anticholinergic effects, which means they are able to block specific neurotransmitters from communicating.
Common Side-Effects of Tricyclics Include:
- Weight gain
- Dry mouth
- Hypotension which can be lethal in overdose
- Trouble sleeping
- Trouble urinating
- Blurred vision
- High Blood Pressure
- Abnormal heart rhythm
Common Tricyclics include:
- Amitriptyline (Elavil
- Clomipramine (Anafranil)
- Desipramine (Norpramin)
- Imipramine (Tofranil)
- Nortriptyline (Pamelor)
Of the medications listed above, clomipramine is the only medication with anti-anxiety properties to be FDA-approved for anxiety disorders.
The brand name drug known as Clomicalm is approved for the treatment of separation anxiety in dogs when used with behavior modification.
Tricyclic antidepressants should not be used with monoamine oxidase inhibitors due to the risk of serotonin syndrome in dogs.
Monoamine Oxidase Inhibitors
Monoamine oxidase inhibitors were introduced in the 1950’s to treat depression.
The three neurotransmitters thought to sustain mental balance include dopamine, serotonin, and norepinephrine. Together, they are known as monoamines.
A chemical found in the body known as mono amine oxidase removes these important transmitters. This particular antidepressants works by preventing mono amine oxidase from removing those all-important neurotransmitters.
Unfortunately, this early anti-depressant comes with a variety of side-effects. They also have a higher risk of drug interactions than standard antidepressants and can interact with certain foods including cheeses and cured meat.
Common Types of MOAI’s include:
- Isocarboxazid (Marplan)
- Phenelzine (Nardil)
- Tranylcypromine (Parnate)
- Selegiline (Eldepryl, Emsam)
Selective Serotonin Reuptake Inhibitors
SSRI’s are a type of antidepressant that work by increasing levels of serotonin in the brain. This “feel good” hormone carries messages between brain cells.
SSRI’s are considered 2nd generation antidepressants and have pretty much replaced the first generation of tricyclic and MAOIs. This is because of their improved tolerability and safety profile.
Common Selective Serotonin Reuptake Inhibitors (SSRI’s) include the following:
Selective Norepinephrine Reuptake Inhibitors
These drugs block the reabsorption of serotonin and norepinephrine into the brain. They help relieve anxiety and depression by changing brain chemistry in a way that recircuits communication between neurons.
Common SNRI’s for Dogs include:
- Desvenlafaxine (Pristiq)
- Duloxetine (Cymbalta)
- Levomilnacipran (Fetzima)
- Venlafaxine (Effexor XR)
Diagnosing Serotonin Syndrome in Dogs
Diagnosis of serotonin syndrome is in dogs is based on the history of ingestion of a serotonergic drug.
Clinical signs of serotonin toxicity are diverse and may not look the same for all veterinary patients. That said, there are some similarities in toxicity the result in gastrointestinal and neurologic clinical signs.
Pet owners with a regular veterinarian are lucky in that he/she will already know what prescriptions the dog is on. It’s vital for pet owners to communicate all other dietary supplements being administered to the dog.
In addition, it’s important to share any possibility that the dog accidentally swallowed a human prescription (and what that is).
Saving a Dog with Serotonin Syndrome
Based on the observation of a clinical overdose, the veterinarian will likely perform all or some of the following:
Physical exam includes observation of signs that may include seizures, muscle rigidity, signs of abdominal pain, problems with the GI tract (vomiting, diarrhea) and mental states of the dog.
Blood tests can eliminate the possibility of infection or other causes.
Neurological testing can also pinpoint specific areas of the nervous system that are affected including the brain or spinal cord. The veterinarian may perform a pink test for response, check for capillary refill time, and check general reflexes.
Supportive & Symptomatic Treatment
Once the doctor suspects a toxic overdose, aggressive treatment is required to thwart this potentially life-threatening condition. The first steps are to try and eliminate as much of the drug from the body as possible. This could include gastric lavage and charcoal.
If or when the dog is stable enough, gastric lavage is used to pump the stomach. This can be done while the drug is still in the stomach to help get rid of excess drug.
Activated charcoal is given to a dog in order to help absorb excess toxins. These toxins are then safely eliminated through the stool.
Supportive care (i.e. intravenous fluids) is used to cool and rehydrate dogs.
This drug is used to treat any seizures the dog may be having as a result of the increase of serotonin in the body.
Anti-emetics are drugs used to control excessive vomiting.
This is used to treat muscle tremors. It is a centrally acting muscle relaxant that can be used with an IV.
NOTE: Analgesic opioids can make serotonin syndrome much worse. This would include drugs like fentanyl and tramadol.
5 Easy Ways to Reduce the Risk of Serotonin Syndrome in Dogs
#1. OUT OF SITE
Keep all human medication out of your dog’ s reach. When a dog wants something, it’s surprising what they’ll do to get it. Sometimes pushing it to the back of the counter isn’t good enough.
#2. RESEARCH SUPPLEMENTS
If your dog is on a prescribed medication, it’s important to understand that other supplements (including the ones marked “all natural” or homeopathic) can have significant and sometimes deadly effects when combined with other things.
#3. GET A DOG TAG
Having a dog tag that lists your dog’s medications can be useful if your dog goes to places like doggy daycare, boarding kennels, etc. If anything were to happen, someone would quickly be able to identify your dog’s condition and medication.
#4. COMMUNICATE WITH FAMILY AND FRIENDS
It’s not that unusual for someone to want to feed your furry friend a treat or two. Be sure to communicate with family and friends so that they are aware of possible drug interactions, specifically with food containing tryptophan.
#5. BE AWARE OF SUBTLE SIGNS
It takes time for antidepressants to work properly and sometimes the first dose doesn’t do the trick. Gradual increases in antidepressant medications could trigger serotonin syndrome.
If your dog suddenly acts differently, seems more tired than usual, or more excitable than usual, be sure to tell the veterinarian right away.
Follow-up Posts to Read Next