Mirtazapine for the Treatment of Chronic Pruritus

Background: Chronic pruritus is a debilitating condition associated with a wide range of dermatologic, systemic and psychogenic etiologies. In patients with chronic pruritus that is refractory to conventional therapy, symptoms can significantly decrease quality of life by contributing to anxiety, sleep disturbances, and in many cases depression. Recent studies have demonstrated the effectiveness of mirtazapine in relieving chronic itch that is refractory to standard first-line therapies. Methods: We searched PubMed for English-language articles containing the words (“pruritus” or “itch”) AND “antidepressant” and then conducted a systematic review of the current literature to summarize the efficacy of mirtazapine in treating chronic itch. Results: All studies reported a reduction in itch intensity following the administration of mirtazapine. Conclusion: Collectively, these studies suggest the potential for mirtazapine to relieve chronic itch attributed to dermatological causes and malignancies. As, such mirtazapine may be an option for patients with chronic pruritus that is refractory to typical first-line treatments.

Dear Editor, Chronic pruritus is a common condition that can interfere with sleep and diminish overall quality of life. The current management of chronic itch is directed at the underlying cause, which can be dermatologic, systemic or psychogenic in nature [1]. First-line therapy typically begins with topical emollients, topical corticosteroids, and antihistamines. GABA-receptor modulators, opioid agonists/antagonists and phototherapy can be used for patients with refractory pruritus [1].
Recalcitrant itch is a distressing symptom for which a safe and effective agent is needed [2,3]. Recent studies have demonstrated the effectiveness of oral antidepressants in relieving chronic itch associated with dermatologic, systemic and psychogenic causes [4,5]. Mirtazapine, a dual noradrenergic and serotonergic antidepressant with antihistaminergic properties, is one such antidepressant that has demonstrated effectiveness in reducing itch severity. As an H 1 , 5HT 2 and 5HT 3 -receptor blocker, mirtazapine may be an alternative therapy for pruritus that is refractory to first-line therapies. Mirtazapine is believed to centrally reduce itch by antagonizing a2-adrenergic receptors [6,7]. Aside from having a wide therapeutic index, mirtazapine is rarely known to cause the initial anxiety and nausea associated with other antidepressants effective in treating chronic itch [2,8]. To assess the efficacy of mirtazapine for the treatment of chronic pruritus, we therefore performed a systematic review of the current literature using PubMed for English-language articles containing the words ("pruritus" or "itch") AND "antidepressant." The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) flow chart is shown in Figure 1. All studies reported a reduction in itch Reviews and Meta-Analysis (PRISMA) flow chart is shown in Figure 1. All studies reported a reduction in itch intensity following the administration of mirtazapine. Collectively, these studies suggest the potential for mirtazapine to relieve chronic itch attributed to dermatological causes and malignancies (Table 1).   Both patients noted a "significant reduction" of nocturnal and daytime pruritus and improvement in sleep. [7] Lichen simplex chronicus 1 15 mg mirtazapine every day for two months.
Patient noted a complete resolution of nocturnal pruritus and "significant reduction" in daytime pruritus. The patient reported a decrease in itch intensity from "200/100" pre-treatment to 2/100 twelve hours after starting mirtazapine. [6] Medicines 2019, 6, 73 4 of 5 There are several limitations to this review. Of the studies evaluated, most were case series or case reports. Larger, randomized controlled trials are still needed to draw definitive conclusions regarding mirtazapine's effectiveness in reducing itch. The studies included used a wide variety of outcome measures to evaluate itch intensity, which limits our ability to directly compare outcomes. Given the significant psychological burden of chronic pruritus, the placebo effect may have also affected perceived outcomes [9].
Mirtazapine is currently FDA-approved for the treatment of major depressive disorder. The main side effects of mirtazapine are heavy sedation, weight gain and hypercholesterolemia [10]. Mirtazapine is contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) given the increased risk of serotonin syndrome [6]. Prior to prescribing mirtazapine, physicians should obtain a baseline lipid panel, liver function tests, and fasting blood glucose levels [11]. The FDA-approved starting dose for mirtazapine is 15 mg orally every night for the treatment of major depressive disorder (MDD) [7,11]. Physicians should counsel patients to report any signs of worsening depression or suicidal ideations upon the initiation of treatment or as a result of dosage changes. It is also advised that physicians schedule a follow-up appointment six-weeks after initiating treatment to evaluate for clinical improvement, drug reactions, or adverse effects.
In conclusion, mirtazapine may be an option for patients with chronic pruritus that is refractory to typical first-line treatments, but future randomized controlled trials are needed to determine the efficacy of therapy, optimal dosing regimens, and the types of chronic pruritus that benefit most from treatment with oral antidepressants.
Author Contributions: R.K., E.B. and S.G.K. conceived and designed the study; R.K. and E.B. conducted the literature review; R.K., E.B., J.G.Z. and S.G.K. analyzed the data; R.K. and E.B. prepared the original draft of the manuscript. R.K. and M.B. reviewed and edited the manuscript; J.G.Z. and S.G.K. supervised the analysis and writing of the manuscript.
Funding: This research received no external funding.