The Course of Tricyclic Antidepressants

Updated on February 16, 2018
Ktina Amber profile image

As a psychology major, I attended a class called psychopharmacology. I grew intrigued with the way substances affected both body and brain.

General Description

Tricyclic antidepressants (TCAs) are one of the two first generation antidepressants. Based on the idea that depression stems from a deficiency in norepinephrine and serotonin neurotransmitters, this drug was intended to increase their levels within the brain (Advokat, 2014). According to Advokat, TCAs relieve symptoms of depressions, not to mention have the significant anxiolytic and analgesic actions. Despite being a first-generation drug, TCAs are known to be just as effective as the commonly used antidepressant today (Advokat). Imipramine, desipramine, amitriptyline, and nortriptyline are types of tricyclic antidepressants. TCA’s are known to elevate moods, increase physical activates, improve appetites, and sleep patterns (Advokat). TCAs are also beneficial as they have been proven to aid in preventing relapse, and have been effective with long-term therapy. TCAs are well absorbed into the bloodstream and are metabolized by the liver. Their half-lives are longer than most drugs, so in order to reduce the impact of their side effects, many take them before they go to bed. There are even TCA’s that have effects that can last up to four days, and perhaps even longer in elder individuals. Advokat does mention that TCAs can cross the placental barrier, however, there have been no known abnormalities.

Mechanism and Pharmacological Effects

Liu (2013) states TCAs are first-line agents for neuropathic pain treatment; they have strong serotoninergic and noradrenergic reuptake inhibition. According to Advokat, TCAs block presynaptic reuptake transporters for the neurotransmitters norepinephrine and serotonin; since they block both, it was considered the first dual action antidepressant. In order to cause their therapeutic effects, TCAs attach to norepinephrine and serotonin presynaptic transporter proteins. Thought they have been proven effective they also have limitations. Three of their main limitations are they have a slower rate of onset, they have more side effect than current antidepressant medications, and finally, in any case of overdose, they can cause cardiac arrhythmias, proving to be fatal (Advokat). Advokat also mentions TCAs block postsynaptic receptors for histamine and acetylcholine; therefore causing their side effects. The side effects consist of drowsiness, sedation, confusion, memory/ cognitive impairments, dry mouth and blurred vision, increased heart rate, and urinary retention (Advokat). It is possible depending on the type of TCA take there is also an additional side effect of weight gain (Liu). Liu states nortriptyline is known to have fewer side effects than amitriptyline, as it has less anticholinergic activity. TCAs may not only be used as antidepressants, they are also good for pain medications. Tricyclic antidepressants can aid with headaches, fibromyalgia, chronic back pain, myofascial pain, and chronic fatigue (Advokat). Reed (2012) states fibromyalgia is a constant and widespread pain, fatigue and stiffness, which also causes depression, anxiety, and cognitive dysfunction. Though TCAs can be used for relieving pains, it is not common, and, in fact, the use of TCAs is actually declining (Reed).

Side Effects

TCA’s block two receptors, the histamine receptors as well as acetylcholine receptors. The blocking of these two receptors causes separate effects. The blocking of histamine receptors causes drowsiness and sedation. The blocking of the acetylcholine receptors causes the more severe of the side effects, which are confusion, memory, and cognitive impairments as well as dry mouth, blurred vision increased heart rates and urinary retention. Advokat implies the side effects impairing cognition and memory can be significant. It is recommended, depending on the age of the patient, that a low potency be administered. Eizadi-Mood (2015) states that despite TCAs are no longer commonly used in the United States; they are still commonly used in other parts of the world. If people attempt to overdose and fail at the attempt of suicide, they will likely face anterograde memory impairment. Though that the impairment can be harmful, it is likely to improve within 24 hours after poisoning. (Eizadi-Mood). Advokat states of the TCA medications released nortriptyline and desipramine were the choice medications as their side effects caused less sedation and cognitive impairment. Advokat states if the prescription is taken long enough that there may be a tolerance built to the possible side effects, however it is not guaranteed. Though cardiac arrhythmias can occur when taken with the purpose of overdosing in suicide attempts, it is urged that if this is given to children. It should be taken with extreme caution as it has been responsible for 12 cases of sudden death (Advokat). Eizadi-Mood explains that TCAs are highly responsible for deaths or even attempts at suicide, as TCA poisoning is frequently the cause of drug-induced deaths.

Tricyclic Antidepressants Abuse

Advokat explains TCA’s are strictly for antidepressants. They do not have any recreational purposes or pose any addictive dangers. Therefore TCAs do not pose much of a concern about being abused or obtaining a psychological dependence.


Advokat, C. D., Comaty, J. E., & Julien, R. M. (2014). Julien's primer of drug action: A comprehensive guide to the actions, uses, and side effects of psychoactive drugs (13th Ed.). New York, NY: Worth Publishers.

Eizadi-Mood, N. (2015). Memory Impairment following acute tricyclic antidepressants overdose. Depression Research and treatment. 2015.4

Liu, W. (2013). Equivalency of tricyclic antidepressants in open-label neuropathic pain study. Acta Neurological Scandinavica. 129. 132-141.

Reed. C. (2012). Real-World Role of Tricyclic Antidepressants in the treatment of Fibromyalgia. Pain practice. 12(7). 533-540.

This content is accurate and true to the best of the author’s knowledge and does not substitute for diagnosis, prognosis, treatment, prescription, and/or dietary advice from a licensed health professional. Drugs, supplements, and natural remedies may have dangerous side effects. If pregnant or nursing, consult with a qualified provider on an individual basis. Seek immediate help if you are experiencing a medical emergency.

© 2018 Kristina


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