Amitriptyline was developed out of a need in human medicine for anti-anxiety medications in the treatment of mental illness though, in humans, it has gained some popularity for the treatment of chronic pain syndromes, especially interstitial cystitis.

This medication creates its effects via several mechanisms:

• By blocking the way cells of the nervous system transport biochemicals called “amines,” amitriptyline is able to increase the levels of circulating neurotransmitters, especially a neurotransmitter called “serotonin.” This mechanism seems to be at the route of amitriptyline’s anti-anxiety and psychoactive properties. This property also is responsible for amitriptyline’s sedation side effect.
   
• The same blockage of the amine pump leads to increased levels of the neurotransmitter “norepinephrine.” Norepinephrine is an important neurotransmitter in the “sympathetic” nervous system.
   
• Amitriptyline is a strong antihistamine.
   

Amitriptyline is a member of the class of drugs called “tricyclic antidepressants.”

 

HOW THIS DRUG IS USED

With amitriptyline becoming widely used in human mental illness, it was not long before small animal uses for this medication came to light. Amitriptyline has been used in animals for separation anxiety, for inappropriate urination in cats, for feline lower urinary tract disease, and for obsessive grooming behaviors in both dogs and cats. In many of these conditions it is not clear which of the above described mechanisms of action are responsible for the desired effects.

 

SIDE EFFECTS

The most common side effect is drowsiness/sedation.

Anticholinergic side effects would probably not be surprising: dry mouth (manifested in animals often as frequently licking of the lips), urinary retention, constipation.

The most potentially dangerous side effect that happens with a realistic frequency is the exacerbation of a cardiac rhythm disturbance.  For this reason, an EKG screening has been recommended before starting this medication.

Tricyclic antidepressants can alter blood sugar levels.

In humans, side effects in virtually every organ system have been reported at one time or another which means that potentially any side effect could be attributed to the use of this medication.

 

INTERACTIONS WITH OTHER MEDICATIONS

Tricyclic antidepressants such as amitriptyline cannot be safely used with monoamine oxidase inhibitors such as Deprenyl (Anipryl®).

The risk developing a dangerously low white blood cell count with the use of methimazole is greatly increased if there is concurrent use of amitriptilline.

The use of Cimetadine (Tagamet^®) can interfere with the desired effect of amitriptyline.

Amitriptyline is best not used in conjunction with other drugs with anticholinergic effects, drugs that stimulate the sympathetic nervous system, or with other psychoactive drugs.

 

CONCERNS AND CAUTIONS

Amitriptyline is removed from the body via the liver. Patients with abnormal liver function may have trouble with this medication.  Periodic liver enzyme evaluation (blood testing) is a good idea for patients on this medication long term.

Amitriptyline should not be used in pregnancy or lactation, in patients with seizure disorders, or in patients with cardiac rhythm disturbances. Diabetic pets should avoid the use of amitriptyline.