Treatment for stubborn pruritus
What is pruritus?
Pruritus (or itching) is themost common symptom of skin diseases. It is rare for a skin disorder to occur with other symptoms, such as pain or burning sensation. Although pruritus can most often be controlled with topical corticosteroid preparations or using oral antihistamines, it is not uncommon for some chronic diseases to cause very intense itching that can reduce the patient’s quality of life .
How important can pruritus be for the patient?
The persistence of this intense discomfort in a repetitive way can lead to the appearance of anxiety, depression and even represent an increased risk of suicide. For these reasons it is especially important to be able to offer the patient, if not the cure of their disease, relief from their symptoms that increases their quality of life.
What diseases can cause itching?
Most of them are of cutaneous origin. Among the most frequent causes of pruritus we find acute diseases such as urticaria, irritative and contact eczema or scabies. But other chronic skin disorders such as atopic dermatitis, lichen simplex chronic, prurigo nodular or psoriasis can cause pruritus that can become unbearable for the patient. Finally, there is another origin of itching: the so-called “internal” diseases. In these, the cause is not cutaneous but the itching is one more symptom of a more complex syndrome. Among them we find liver failure, kidney failure, cholestatic syndromes, metabolic diseases (diabetes, thyroid disorders) or neoplasms, whether blood or of some solid organ. It is precisely in this type of internal diseases that pruritus can become the worst tolerated symptom and that most affects the patient’s quality of life.
Can pruritus indicate a serious illness?
Yes. It is not a frequent phenomenon, but sometimes the presence of persistent itching on the skin, without observing primary skin lesions to explain it, can be the first symptom of a serious disease. Usually, if pruritus occurs, it is a symptom throughout the course of a known disease . However, some neoplasms such as leukemias, lymphomas or a digestive tumor that causes a reduction in bile flow can debut with this symptom. Other disorders that can cause itching without skin lesions are diabetes, thyroid dysfunction or iron deficiency. For these reasons, it is important to consult your dermatologist when itching lasts more than two weeks. If appropriate, your dermatologist will ask you for the necessary tests after the examination and medical history to study the origin of your itching.
Why does itching appear?
Although it is the most frequent symptom of skin diseases, the precise mechanisms by which the sensation of itching is felt are unknown . The transmission of this symptom is carried out through the same nerve fibers through which pain is emitted (“C” fibers). Some of the most important mediators to generate itching are two substances called histamine (which acts on its H1 receptors) and serotonin (which binds to its receptors 5HT2 and 5HT3).
How is severe itching usually treated?
Pruritus that requires oral treatment to be relieved usually benefits from histamine H1 receptor blockers (antihistamines) and/or serotonin blockers (selective serotonin reuptake inhibitors, SSRIs). Antihistamines are the oral drug of choice with which anti-pruritic therapy is initiated. These include cetirizine, loratadine, ebastine, dexchlorpheniramine and hydroxyzine, to name the most commonly used. The most common side effect of antihistamines is drowsiness resulting in blockage of histamine H1 receptors. Unfortunately, antihistamines are not usually useful for the control of pruritus associated with renal or hepatic failure, cholestatic or secondary to a neoplasm.
SSRIs are usually more effective in the treatment of pruritus secondary to an internal disease. The most commonly used in these stubborn cases are ondansetron and paroxetine. However, ondansetron is a particularly expensive drug and both ondansetron and paroxetine have numerous drug interactions with other drugs.
What is mirtazapine?
Mirtazapine is a drug that blocks histamine H1 receptors and serotonin receptors 5HT2 and 5HT3. Although these receptors are the ones that transmit the sensation of itching, this is not their basic function and their activity is mainly related to the person’s mood. For this reason, mirtazapine is taxonomically classified as an antidepressant drug and not an antipruritic drug.
What advantage can mirtazapine have over other antipruritic treatments?
Its main virtue lies in its action, as it blocks the three main receptors involved in the transmission of pruritus. Therefore, it has a higher effectiveness profile than antihistamines for the treatment of pruritus secondary to kidney, liver or neoplastic diseases. Compared to other alternatives for stubborn internal pruritus such as SSRIs, it does not have as many drug interactions and its administration is by a single daily dose, so it is a more comfortable, safer and easier treatment for the patient. In addition, it does not require adjusting the dose even if kidney or liver failure is present. Another favorable secondary aspect is its low economic cost.
What side effects can mirtazapine have?
Due to the blockade it exerts on histamine H1 receptors, it can cause drowsiness (which is why it is administered at night) and a tendency to gain weight. However, when used in patients with chronic pruritus associated with a serious disease, it improves sleep quality, lack of appetite, depression and cachexia associated with cancer.
So, is mirtazapine useful for treating any type of itching?
No, nor is it the initial option in most cases. It is very useful for pruritus secondary to a serious disease, which deteriorates the patient’s quality of life or in cases where other therapies have failed. In addition to being used in pruritus secondary to internal diseases, it is useful in the treatment of nodular prurigo and other disorders that occur with the itch and scratch circle .
REFERENCES
· Davis MP, Frandsen JL, Walsh D, Andresen S. Mirtazapine for pruritus. Journal of Pain and Symptom Management; vol. 25(3): 288-291.
Thanks to Dr. Oriol Yélamos for focusing interest on mirtazapine therapy and sharing his knowledge.