The Journal of Allergy and Clinical Immunology
Volume 123, Issue 2 , Pages 504-505, February 2009

Successful treatment of chronic drug-resistant urticaria with alprazolam

  • Antonio Dueñas-Laita, MD, PhD

      Affiliations

    • Servicio de Farmacología Clínica–Unidad Regional de Toxicología Clínica, Hospital Universitario Río Hortega, Valladolid, Spain
    • ,
  • Pedro Ruiz-Muñoz, MD

      Affiliations

    • Asociación Castellano Leonesa de Ayuda a Drogodependientes, Valladolid, Spain
    • ,
  • Alicia Armentia, MD, PhD

      Affiliations

    • Sección de Alergia, Hospital Universitario Río Hortega, Valladolid, Spain
    • ,
  • Florentino Pinacho, DUE

      Affiliations

    • Servicio de Farmacología Clínica–Unidad Regional de Toxicología Clínica, Hospital Universitario Río Hortega, Valladolid, Spain
    • ,
  • Blanca Martín-Armentia, PhT

      Affiliations

    • Servicio de Farmacología Clínica–Unidad Regional de Toxicología Clínica, Hospital Universitario Río Hortega, Valladolid, Spain

Article Outline

 

To the Editor:

Alprazolam has shown competitive antagonism on muscarinic and histamine H1 receptors and noncompetitive antagonism on histamine H2 receptors. The antagonistic effect of alprazolam on histamine H1 receptors has been studied in guinea pig ileum, and that on histamine H2 receptors has been studied on rat uterus.1 Pretreatment with kadsurenone or alprazolam improved survival in hypersensitivity reactions to ovalbumin in guinea pig lung parenchymal strips and in guinea pigs in vivo.2 This antihistaminic effect has not been tested in allergic patients, although one study found that alprazolam appeared to be safe and effective for the treatment of anxiety and depression in adolescents with asthma.3 Exceptionally, alprazolam might induce allergic symptoms and angioedema.4

Chronic urticaria (CU) is a common disorder that is generally of unknown origin, although the cause might be autoimmune in some cases.5 In some patients severe urticaria is a distressing and disabling condition6 with a significant effect on the quality of life, and patients often receive various unsuccessful treatments. First-line treatment consists of the newer-generation oral antihistamines, whereas other drugs might be considered in refractory cases,7 although more controlled studies are necessary.

We recently studied allergic sensitization in drug abusers, who are often treated with alprazolam. Forty-two drug abusers were tested with common allergens (aeroallergens and foods) and pharmacologic drugs (nonsteroidal anti-inflammatory drugs and other suspected drugs). Histamine (10 mg/mL) was used as a positive control, and a wheal area greater than 7 mm2 (an area measuring 3 × 3 mm) was considered positive. In some patients skin prick test responses with allergens were negative, but results with histamine, used as a positive control, were also totally negative. This is unusual because the histamine control should elicit a small wheal, even when the patient has taken an antihistamine. These patients denied intake of antihistamines or other antiallergic drugs, but all were taking 2 mg of alprazolam (Trankimazin; Pfizer S. A., Madrid, Spain) 3 times daily. We then decided to carry out a preliminary study to investigate whether alprazolam could be useful in severe refractory CU.

We identified 558 patients with idiopathic CU in our database of 19,736 patients followed in the allergy section during the last 20 years. All patients had undergone a protocol investigation according to recent studies5, 6 to investigate the possible cause. Only 12 of the 558 patients had criteria of severe refractory idiopathic urticaria of more than 10 years of evolution in which treatment with all known drugs used in this disease (all first-generation antihistaminics,8 all newer-generation antihistamines, corticosteroids in different schemes, cyclosporine treatment,9 intravenous gammaglobulin,10 and omalizumab11) had failed. The 12 patients were initially randomized to 2 mg of alprazolam 3 times daily or 10 mg of rupatadine (Rupafin; Uriach, Barcelona, Spain) 3 times daily, a new antihistamine platelet-activating factor (PAF) inhibitor. The drugs were introduced into identical empty capsules and administered randomly by a nurse blinded to the contents. However, only 8 patients finally consented to participate and completed the trial.

After 2 days, the urticaria disappeared in the 6 patients treated with alprazolam and persisted in the 2 patients treated with rupatadine. No secondary effects were observed. Urticaria reappeared after 36 hours after withdrawal of alprazolam and improved 8 hours after readministration.

Although both alprazolam and rupatadine are PAF receptor antagonists,1, 2 the poor response to rupatadine suggests that the main mechanism of alprazolam in CU might be blockade of histamine H1 receptors and not PAF inhibition. The importance of this small study lies in the fact that 6 of 6 patients treated with alprazolam responded, whereas the 2 patients treated with rupatadine did not.

Because of the difficulty in identifying the causative factors involved, treatment for severe CU often focuses on measures to provide symptomatic relief. Our positive experience, although only in a small group of patients, suggests a controlled trial with alprazolam in a large group of patients with drug-resistant CU is necessary.

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References 

  1. Alvarez FJ, Velasco A, Palomares JL. Blockade of muscarinic, histamine H1 and Histamine H2 receptors by antidepressants. Pharmacology. 1988;37:225–231
  2. Darius H, Smith JB, Lefer AM. Inhibition of the platelet activating factor mediated component of guinea pig anaphylaxis by receptor antagonists. Int Arch Allergy Appl Immunol. 1986;80:369–375
  3. De Vance Cl, Hill M, Antal EJ. Therapeutic drug monitoring of alprazolam in adolescents with asthma. Ther Drug Monit. 1998;20:257–260
  4. Sellas-Dupre G, Nieto Lopez M, Garcia Vicente JA, Salvador–Chiva J. Alprazolam-induced tongue angioedema. Pharmacopsychiatry. 2006;39:154–156
  5. Hide M, Francis DM, Gratton CE, Hakimi J, Kochan JP, Greaves MW. Autoantibodies against the high affinity IgE receptor as a cause of histamine release in chronic urticaria. N Engl J Med. 1993;328:1599–1604
  6. Deacock SJ. An approach to the patient with urticaria. Clin Exp Immunol. 2008;153:151–161
  7. Morel V, Hauser C. Chronic urticaria. Rev Med Suisse. 2008;4:1019–1023
  8. Kaplan AP. Chronic urticaria: pathogenesis and treatment. J Allergy Clin Immunol. 2004;114:465–474
  9. Serhat Inaloz H, Ozturk S, Akcali C, Kirtak N, Tarakcioglu M. Low-dose and short-term cyclosporine treatment in patients with chronic idiopathic urticaria: a clinical and immunological evaluation. Dermatology. 2008;35:276–282
  10. Pereira C, Tavares B, Carrapatoso I, Loureiro G, Faria E, Machado D, et al. Low-dose intravenous gammaglobulin in the treatment of severe autoimmune urticaria. Eur Ann Allergy Clin Immunol. 2007;39:237–242
  11. Spector SL, Tan RA. Omalizumab also successful in chronic urticaria. J Allergy Clin Immunol. 2008;121:784–785

 Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.

PII: S0091-6749(08)02355-5

doi:10.1016/j.jaci.2008.12.005

The Journal of Allergy and Clinical Immunology
Volume 123, Issue 2 , Pages 504-505, February 2009

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