Sometimes opioids, gabapentinoids may be best treatment for itching
LAS VEGAS — Antihistamines are not always the answer for pruritis in pain and advanced illness, Laura Meyer-Junco, PharmD, BCPS, CPE, said during a presentation at PAINWeek 2022.
The clinical assistant professor and clinical pharmacist from the College of Pharmacy at the University of Illinois Chicago told attendees that gabapentinoids, topical anesthetics, antidepressants and opioid antagonists are sometimes the better choice.
“Itching, like chronic pain, can have a significant impact on quality of life,” Meyer-Junco said. “And it’s our business to reduce misery.”
However, it is important to note that drugs used for pain — specifically, opioids — can also cause pruritis.
Pain and itch have several things in common in addition to their impact of quality of life, Meyer-Junco said. They can both be chronic; the processes of nociception and pruriception can have shared clinical mediators; pain and itch can be neuropathic, neurogenic or psychogenic; sensitization is common to both; and they can have an antagonistic relationship.
Chronic pruritis of unknown origin is common, especially in older adults, she said. Those older than 80 years have the greatest incidence of pruritis. However, she noted that the side effect profile of antihistamines, which includes sedation, is not “geriatric-friendly.”
“Like pain, pruritis can have peripheral or central origins,” Meyer-Junco said. “If you’re going to get to the bottom of how to treat it, learn how to classify it. Does it come from the skin or somewhere else?”
Itching can be pruritoceptive (originating in the skin), neuropathic (due to damage to peripheral or central sensory neurons) or neurogenic (related to systemic disease).
“Don’t just throw antihistamines at patients,” Meyer-Junco said. “Use questions to evaluate them.”
Ask if the itch is localized or generalized and what it looked like when it first began. Pruritoceptive pruritis should be referred to a dermatologist, she said. Histamine may cause an acute rash or hives, in which case topical or oral therapy would be indicated.
Skin that is noninflamed but with localized itch might indicate neuropathic pruritis, and treatment options could include oral gabapentinoids, capsaicin, anesthetics or menthol, she said.
“In some cases, patients who have a neurogenic pruritis may have localized itching,” Meyer-Junco said. “If the itch is due to a systemic disorder, it tends to be generalized, and there may be no changes to the skin. It could be drug induced [or related to] hematological conditions or metabolic/endocrine conditions. Use centrally acting agents, such as gabapentinoids, selective serotonin reuptake inhibitors or opioid antagonists.”
Itchy, dry skin can be managed in a number of ways, including cooling therapy, humidifiers and cooled lotions or creams.
“Reserve sedating antihistamines for nocturnal itch,” she said. “I’d rather do something more targeted.”
Relaxation therapy and stress reduction should also be considered.
Doxepin 5% cream, a topical antihistamine, has been shown to be helpful, Meyer-Junco said. However, topical steroids do not have a direct antipruritic effect.
“Growing evidence is supporting the role of the [transient receptor potential (TRP)], or ‘hot and cold’ receptor, in the pathogenesis of itch and its treatment,” she said. “In addition, a topical anesthetic could be helpful for histaminergic and nonhistaminergic afferent neurons.”
Meyer-Junco also discussed the neurobiology of itch.
“Chronic pruritis may become its own entity due to the central desensitization that occurs,” she said. “Drugs we use for neuropathic pain could be helpful, like gabapentin or pregabalin, in chronic itching unresponsive to other treatments.”
Other options include paroxetine, sertraline, fluvoxamine and mirtazapine.
In neurogenic pruritis, itching is induced by systemic disease or the use of opioids.
“The role of histamine in opioid-induced pruritis has been contested,” Meyer-Junco said. “Maybe there’s a centrally mediated mechanism. It may be direct binding of new receptors in the dorsal horn of the spinal cord.”
When considering management strategies for opioid-induced pruritis, “try switching routes,” she said. The incidence of pruritis is greater with intrathecal administration, which is greater than epidural, which is greater than IV, which is greater than oral.
Reduce the dose or try co-administration of neuraxial opioids with local anesthetic. Other options include using an opioid antagonist with or without a K-receptor agonist or antihistamine, if appropriate.
“It may be helpful to rotate the opioids,” Meyer-Junco said. “There’s a higher incidence for histamine release with morphine, codeine and meperidine and a lower incidence with fentanyl and oxymorphone, with less histamine release as the potency increases.”