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Melatonin for Primary Immune-Mediated Thrombocytopenia (ITP)

whelan_mg_7312-webBy Megan Whelan, DVM, DACVECC, CVA
www.angell.org/emergency
emergency@angell.org
617-522-7282

Melatonin is a naturally occurring compound that is found in animals, plants such as St. John’s wort, and microbes.1 It is classified by the United States Food and Drug Administration as a dietary supplement and can be bought at supermarkets, commonly in 3 mg capsule form. In comparison, in the United Kingdom it is available by prescription only.1 Due to the fact that it is a supplement, and not a drug, other ingredients may be found in the product.

In mammals, melatonin is synthesized from the dietary amino acid tryptophan. Melatonin is produced by the pineal gland and released into the bloodstream therefore it is a hormone. Melatonin is involved in the circadian rhythm and acts as a free-radical scavenger. In human medicine it has been used for a number of medical issues such as mood disorders, immune disorders, obesity etc. In general, it has minimal side effects, but humans have described feeling drowsy after taking it.

In animals, its use has been reported in alopecia cases such as Alpoecia-X or flank alopecia, and anecdotally in cases of older animals that have cognitive dysfunction for aiding in sleep. The dose range in Plumb’s Veterinary Drug Handbook2 in dogs is 3-6 mg PO SID or BID depending on the weight of the patient or as an implant. Regular melatonin should be used instead of the rapid release or extended release formulations. More recently, it has been suggested as a non-immunosuppressive, alternative agent that can be used for immune diseases such as primary immune-mediated thrombocytopenia (ITP). In the human literature, there are reports of its use for refractory ITP in 3 cases3 and to stop severe bleeding symptoms in one case of ITP.4 There is little information on this supplement in veterinary literature, but it is thought that melatonin stimulates platelet generation by promoting the megakaryocyte fragmentation and modulating the cytokines that are involved in the production of platelets.5 Primary ITP is a disease caused mainly by destruction of platelets, that is why treatment efforts are focused on immunosuppression. However, if platelet production could be increased in the blood via the use of melatonin,this may help prevent life threatening bleeds and the need for transfusions.

In conclusion, melatonin appears to be a safe supplement with minimal side effects. However its efficacy in canine ITP has yet to be determined. Anecdotally, I have used it in a refractory ITP case that did eventually go into remission, but it is difficult to say if it was just the additional time on the immunosuppressive drugs or if it was the addition of this supplement that caused the improvement. The efficacy of melatonin in this disease warrants further investigation in canines due to its minimal cost and minimal side effects. A double-blind, placebo-controlled, prospective study would need to be conducted comparing dogs that received either prednisone and melatonin or prednisone alone for primary ITP.

For more information about Angell’s Emergency/Critical Care service, please visit www.angell.org/emergency. Dr. Whelan can be reached at 617-522-7282, or by e-mailing emergency@angell.org.

References:

  1. http://en.wikipedia.org/wiki/Melatonin
  2. Plumb, DC. Plumb’s Veterinary Drug Handbook, 7 th Edition.
  3. Todisco M, Rossi N. Melatonin for refractory idiopathic thrombocytopenic purpura: a report of 3 cases. Am J Ther 2002; 9(6):524-526.
  4. Todisco M, Casaccia P, Rossi N. Severe bleeding symptoms in refractory idiopathic thrombocytopenic purpura: a case of successfully treated with melatonin. Am J Ther 2003; 10(2):135-136.
  5. Nakamura RK, Tompkins E, Bianco D. Therapeutic options for immune-mediated thrombocytopenia. J Vet Emerg Crit Care. 2012; 22(1): 59-72.

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