By: Dr. Judy Korman, VMD, MBA


hand holding red pill in front of old brown and white dog

If your dog is suffering from separation anxiety, you may be wondering if prescription drugs are a good idea. Will medication change your dog’s personality? Will they turn into a “zombie” because of excessive sedation? What about other side effects, including any long-term safety concerns? And if your dog starts taking medication for anxiety, will they have to stay on it forever?


As with any drug your dog might take, anti-anxiety drugs – also commonly referred to as anxiolytics or anti-depressants – are not without their risks. Side effects vary depending on the type of medication, dosage, and length of treatment, as well as the dog’s sensitivity to the drug. But anti-anxiety drugs are generally well-tolerated by dogs and can provide much-needed relief and support in certain situations, especially when the separation anxiety is chronic or severe. Also, keep in mind that drugs are not necessarily the last resort when all other treatment options have failed. Starting a dog on medication sooner, rather than later, can be more beneficial in the long run.


Please note that this article is for informational and educational purposes only. Pet owners should not give any medications, prescription, or even over-the-counter, without first discussing it with their pet’s veterinarian.


How Do Medications Help with Anxiety?


In our brains, chemicals called neurotransmitters send messages between nerve cells, affecting the way we function – both physically and psychologically. Certain neurotransmitters, such as norepinephrine, serotonin, dopamine, and gamma-aminobutyric acid (GABA), are associated with mood. Anti-anxiety medications boost the levels of these different neurotransmitters either by increasing their production and release from neurons and/or blocking them from being reabsorbed back into the nerve cells – resulting in an overall happier, less anxious feeling for the dog.


Medication isn’t a cure for separation anxiety — there is no “magic pill” that will take your dog’s stress away. Instead, prescription drugs are a tool that can help decrease a dog’s physical response to stress, which is what leads to behavioral issues, such as barking, destructiveness, and even self-harm.


Research and anecdotal evidence have shown that for successful and long-term results, medication should always be used in conjunction with behavior modification and training. Although behavior modification and training can be highly effective when used alone, some dogs make better progress, faster, with the support of medication. Stress can short-circuit a dog’s potential to learn new ways to respond. Anti-anxiety medication helps calm their negative emotional response, so they’re more receptive to training while reducing their risk of regression.


Ideally, as a dog learns new coping skills and becomes less anxious about being away from their owner, they will become less dependent on medication. Of course, the goal is to eliminate the need for medication, but dogs struggling with severe, chronic anxiety may require lifelong treatment to manage their symptoms and improve their quality of life.


Medication Options


Two main types of drugs are used to treat anxiety in dogs: long-acting and short-acting. The majority of these medications are FDA-approved for treating depression and anxiety symptoms in humans and have been widely prescribed “off-label” by veterinarians for many years.

  • Long-Acting – Given daily, long-acting medication serves as a maintenance treatment for separation anxiety in dogs. It can take several weeks or longer before these drugs reach their full effect, and they should not be stopped suddenly. Dogs that are left alone frequently for longer periods — such as four or five times per week for six or more hours a day — are better candidates for long-acting drugs.
    • Tricyclic Antidepressants (TCAs) are an older class of antidepressants with substantial research to support their use in both humans and dogs. TCAs work by increasing the levels of norepinephrine and serotonin in the brain. Clomipramine (Clomicalm®) is approved for canine use, but other human-approved antidepressants, such as amitriptyline (Elavil®), may be indicated. Because TCAs are less refined in the way they work, there’s a greater potential for side effects. The most common ones are sedation, dry mouth, lack of appetite, vomiting, diarrhea, and restlessness. Some of these reactions can be used to the dog’s advantage and may be desired. For example, a dog that drools excessively when left alone may benefit from a drier mouth, or the sedative effect of a TCA could help a dog that becomes frantic when alone.
    • Selective Serotonin Reuptake Inhibitors (SSRIs) are a newer class of antidepressants that are more targeted than TCAs, blocking the reabsorption of serotonin. Currently, fluoxetine is the only SSRI approved for use in dogs with separation anxiety. It is commonly prescribed in its generic form and is also available by the brand name Reconcile®.  Other SSRIs are frequently used off-label for dogs include paroxetine (Paxil®) and sertraline (Zoloft®).  The most common side effects of SSRIs are sedation, loss of appetite, vomiting, diarrhea, and changes in behavior, such as anxiety and hyperactivity. In general, the side effects of SSRIs tend to be fewer and milder than the ones associated with TCAs. In addition, SSRIs may require administration for 6 weeks or longer to have full effects.

  • Short-Acting – These types of as-needed drugs take effect quickly — often within 30–60 minutes — and typically last four to six hours. Short-acting drugs are most commonly used for dogs that are triggered by certain situations, such as thunderstorms or car rides. Dogs with separation anxiety that are left alone infrequently for brief periods are also candidates for short-acting drugs. In addition, these drugs can be used as an add-on with some antidepressants and SSRIs to increase their effectiveness, or during the ramp-up period before the long-acting drugs take full effect.
    • Benzodiazepines (BZs) are sedatives that produce a calming effect by enhancing the level of GABA in the central nervous system. This class of drugs includes alprazolam (Xanax®), clorazepate (Klonopin®), and diazepam (Valium®), among others. Side effects include sedation, as well as sleeplessness, and increased anxiety. BZs are also known to impact learning and memory and can lead to physical dependence, so short-term use is typically recommended.
    • Trazodone (Oleptro® and Desyrel®) is an antidepressant that affects serotonin levels, similar to the target of SSRI medications. However, this medication has a different mechanism of action. It is often used to treat situational anxiety (e.g., car travel, veterinary visits, or thunderstorms) because it can take effect within one to two hours. Reported side effects range from lethargy to hyperactivity and aggression. One note of caution: using trazodone in combination with an SSRI could potentially increase the risk of serotonin syndrome — a potentially life-threatening condition that occurs when the serotonin levels in the body are too high. 
    • Acepromazine is a tranquilizer that has been used to treat anxiety in animals for many years. However, the primary action is on “motor activity” rather than on the animal’s emotional state, and may have the result of immobilizing the dog but without truly relieving or reducing underlying anxiety. Acepromazine can cause some concerning side effects, including confusion, low respiratory rate, low blood pressure, and cardiovascular problems. For these reasons, acepromazine is typically best reserved for emergencies, such as when a dog’s safety is at risk, and is generally used in combination with other anti-anxiety medications for best effect.


Other Medications That Might Help


Over-the-counter antihistamines, such as diphenhydramine (Benadryl®) and cetirizine (Zyrtec®) relieve allergy symptoms in both humans and dogs. Because certain antihistamines (e.g., Benadryl) can cause drowsiness, they are sometimes used to help calm dogs with anxiety. Before turning to one of these drugs, it’s important to talk with your veterinarian, especially if your dog has a pre-existing health condition or is taking other medications. Your veterinarian can also determine the correct dosage for your dog.


Although NSAIDs (non-steroidal anti-inflammatory drugs) are prescribed for pain relief, this type of medication can sometimes play an important role in your dog’s anxiety treatment plan. That’s because the pain from arthritis or another health condition increases overall stress in the body and contributes to anxiety — just like in humans. If your dog isn’t feeling well, they will have a lower tolerance for stress and could struggle with their training.


Similarly, if your dog is experiencing discomfort from allergic or atopic dermatitis and that discomfort is negatively impacting their anxiety level, your veterinarian may suggest Apoquel® or another medication to help with itching and overall irritability. Apoquel is FDA-approved for use in canines and has fewer reported side effects than antihistamines, although has been reported to cause aggression in some dogs.


Starting Your Dog on Anti-Anxiety Medication


The first stop is your veterinarian or veterinary behaviorist, who will consult with you about the severity and duration of your dog’s symptoms and your home situation and goals. From there, you can decide together if an anti-anxiety medication makes sense. Treating your dog’s separation anxiety is a journey, and trialing multiple medications may be needed before finding the one that has the desired effect for your dog. Your veterinarian is there to help you — and your dog — sort through all the options.


Although humans and dogs share similar medications for anxiety and other conditions, you should never give your dog a human-prescribed drug without your veterinarian’s approval.


If you choose to go the pharmaceutical route, your veterinarian will take into account other medications or supplements your dog might be taking and any existing health conditions they might have. Your veterinarian may also want to perform blood work before starting your dog on any medication. Periodic blood tests during your dog’s treatment might also be required to monitor liver and kidney function.


Based on your dog’s tolerance and response to the prescribed medication, your veterinarian can adjust dosage levels or recommend a different prescription for your dog to try. Long-acting medication should not be stopped suddenly without first speaking with your veterinarian. Your veterinarian may also be able to suggest non-pharmaceutical options to use in conjunction with your dog’s medication, including calming supplements, pheromones, anxiety wraps, and Calmer Canine®, a new non-prescription device that has been proven to reduce anxiety in dogs.


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