Selective serotonin reuptake inhibitors are effective in the treatment of polycythemia vera–associated pruritus

Polycythemia vera is a clonal hematopoietic stem cell disorder characterized by erythropoietin-independent erythrocytosis that is often accompanied by splenomegaly, thrombocytosis, and leukocytosis.1 The disease is associated with life-threatening thrombohemorrhagic complications and a progressive risk of transformation to either myelofibrosis with myeloid metaplasia or acute myeloid leukemia. Pruritus, which is often exacerbated by contact with water, occurs in more than 50% of patients with polycythemia vera and may be the most agonizing aspect of the disease, depriving patients of sleep and interfering with their social and physical activities.2 Phlebotomy with or without cytoreductive therapy, the standard treatment for polycythemia vera, is often ineffective in alleviating disease-associated pruritus. More recently, the use of interferon alpha as a cytoreductive agent in polycythemia vera has proven particularly effective in controlling pruritus.3 However, cytoreductive treatment in polycythemia vera is generally reserved for high-risk patients, and the antipruritic benefit of interferon alpha is undermined by the well-known side effects of the drug. On the other hand, symptomatic treatment with antihistamines is often ineffective.

On the basis of a serendipitous anecdotal observation as well as reports of efficacy in pruritus associated with advanced cancer,4 10 patients (median age, 68 years; 3 female) with polycythemia vera–associated intractable pruritus were treated with selective serotonin reuptake inhibitors. Nine patients received paroxetine (20 mg/d) and 1 received fluoxetine (10 mg/d). All 10 patients had a favorable initial response, which included complete or near-complete resolution of pruritus in 8 patients (80%). Response to treatment occurred within 48 hours in most patients. Two patients have discontinued treatment because of either side effects or leukemic transformation. One of these 2 patients had a partial relapse (loss of “best” response but severity of pruritus still better than baseline) of her pruritus before discontinuing treatment with paroxetine. Eight patients are still on treatment for a period of 1 to 12 months. Among these patients, 3 have experienced side effects including delayed ejaculation, decreased libido, and fatigue. Only 1 patient has had a partial relapse in pruritus.

The current report suggests that a selective serotonin reuptake inhibitor may be considered as a therapeutic option in polycythemia vera–associated pruritus. A prospective, controlled treatment trial that is accompanied by laboratory correlative studies is required to validate the current preliminary observations as well as clarify the mechanism of action.

Both authors contributed equally to the work.