I have a question about antihistamine and weight gain. I have seen a female patient with recurrent spontaneous urticaria. Her urticaria is well responded to antihistamine, although not full control. However, she is experiencing a significant weight gain since she has been on zyrtec. Her weight has increased about 2 lbs/month since zyrtec was started. Zyrtec was replaced with Allegra with no improvement. Secondary causes such as hypothyroid or cushing were ruled out. I have known that weight gain is a possible, although not very common, complication of antihistamine therapy but am aware that they might be just coexistence. The problem is she realized that she needs to continue antihistamine to control her hives but was reluctant to increase the dose. She asked me to find an alternative or the antihistamine that has least effect of weight gain. Could you please give me some suggestions regarding this case?


Thank you for your inquiry.

It has long been known that the administration of antihistamines can cause weight gain. In fact, one antihistamine, cyproheptadine, has been used for this purpose. There are many postulations as to why this occurs. One reason, which may be the most reasonable, is that histamine is known to reduce the appetite, and antihistamines, therefore, counteract this effect.

In a recent NHANES survey, antihistamine use was associated with obesity, and a study in the journal “Obesity,” (see abstract copied below) confirmed this and analyzed the use of over-the-counter antihistamines and their effect on weight gain. They found, as in the NHANES survey, that the use of over-the-counter antihistamines, including both fexofenadine and cetirizine, was associated with obesity.

Unfortunately, we know more about this association and the potential underlying reasons for it than we do about which antihistamines may be less likely to produce this effect. I know of no study comparing the effects of available antihistamines on weight gain and could find none on a literature search. Therefore, although it is not unlikely that some antihistamines may be more potent than others in this regard, the effect appears to be more class-related rather than drug-specific.

But because we have no available information on relative potency of antihistamines regarding their effect on weight gain, there is, to my knowledge, no information available to assist you in selecting a specific antihistamine that might be helpful and not produce this side effect. Therefore the only strategy available to you, if you wish to continue to use antihistamines, is to employ various agents via “trial and error.”

The other strategy of course would be to use alternative agents to supplement or replace antihistamine use. A thorough discussion of these drugs are available in two articles.
1.Morgan M and Khan DA. Annals of Allergy, Asthma, and Immunology 2008; 100:403-411.

2.Morgan M and Khan DA. Annals of Allergy, Asthma, and Immunology 2008; 100:51-526.

In summary, to my knowledge, there is no specific antihistamine which will not potentially cause the well-documented side effect of weight gain with regular use, and therefore the only alternative for you is to try different antihistamines in a “trial and error” fashion, or to supplement or substitute the use of antihistamines with alternative therapies. References and abstracts of references are copied below should you wish to read further about the issue of antihistamines and weight gain.

Thank you again for your inquiry and we hope this response is helpful to you.

Volume 18, Issue 12, pages 2398–2400, December 2010
The incidence of obesity in the United States has reached epidemic proportions. Previous research has shown several medications exert noticeable effects on body-weight regulation. Histamine-1 (H1) receptor blockers commonly used to alleviate allergy symptoms are known to report weight gain as a possible side effect. Therefore, we investigated the association between prescription H1 antihistamine use and obesity in adults using data from the 2005–2006 National Health and Nutrition Examination Survey (NHANES). Adults taking prescription H1 antihistamines were matched by age and gender with controls and compared on the basis of body measurements, plasma glucose, insulin concentrations, and lipid levels. Prescription H1 antihistamine users had a significantly higher weight, waist circumference, and insulin concentration than matched controls. The odds ratio (OR) for being overweight was increased in prescription H1 antihistamine users. H1 antihistamine use may contribute to the increased prevalence of obesity and the metabolic syndrome in adults given these medications are also commonly used as over-the-counter remedies.

Expert Opin Pharmacother. 2012 Dec;13(18):2613-24. doi: 10.1517/14656566.2012.742887. Epub 2012 Nov 10.
Potential benefits of cyproheptadine in HIV-positive patients under treatment with antiretroviral drugs including efavirenz.
Dabaghzadeh F, Khalili H, Ghaeli P, Dashti-Khavidaki S.
Tehran University of Medical Sciences, Department of Clinical Pharmacy, Faculty of Pharmacy, Enghelab Ave, Tehran, Iran.
Introduction: More than 50% of HIV-positive patients experience neuropsychiatric adverse reactions following efavirenz therapy. Discontinuation of efavirenz due to its neuropsychiatric side effects has been reported in 2 - 13% of patients. Dizziness, headache, nightmares, abnormal dreams, mild cognitive difficulty, sleep disturbance (somnolence and insomnia), impaired concentration, depression, hallucination, delusion, paranoia, anxiety, agitation, aggressive behavior, mania, emotional labiality, catatonia, melancholia, psychosis, and fatigue are the most reported efavirenz adverse reactions.
Areas Covered: In this review, potential benefits of cyproheptadine in prevention and management of HIV/antiretroviral-associated neuropsychiatric complications are evaluated. The available evidence was collected by searching Scopus, PubMed, Medline, Cochrane central register of controlled trials, and Cochrane database systematic reviews.
Expert Opinion: Cyproheptadine is a cheap and safe drug that does not have significant interactions with antiretroviral drugs. Cyproheptadine's common side effects including increasing appetite and weight gain can be useful in HIV-positive individuals with their decreased appetite and weight loss. There is limited evidence regarding the effectiveness of cyproheptadine in neuropsychiatric disorders. It is essential to evaluate cyproheptadine efficacy in the prevention and management of neuropsychiatric complications of HIV/antiretroviral infection in well-designed studies in the future.

Curr Med Chem. 2010;17(36):4587-92.
Neuronal histamine and its receptors: implication of the pharmacological treatment of obesity.
Masaki T, Yoshimatsu H.
Department of Internal Medicine 1, Faculty of Medicine, Oita University, 1-1 Idaigaoka,Yufu-Hasama, Oita, 879-5593, Japan.
Obesity is the effect of imbalance between energy intake and expenditure and forms a fundamental basis of the metabolic syndrome. A number of substances implicated in the regulation of energy metabolism represent opportunities for anti-obesity drug development. Neuronal histamine and its receptors have been shown to regulate energy metabolism and are considered as anti-obesity targets. Several histamine receptor subtypes have been identified; of these, histamine H1 and H3 receptors (H1-R and H3-R) have been specifically recognized as mediators of energy intake and expenditure. In addition, several histamine drugs related to H1-R and H3-R, have been shown to attenuate body weight gain both in rodent and human. These results provide the reagents for histamine receptors biology and may find applications in the treatment of obesity and related metabolic disorders. In this review, the development of agonists and antagonists of histamine receptors are provided.

Clineschmidt BV, Lotti VJ. Histamine: intraventricular injection suppresses ingestive behavior of the cat. Arch Int Pharmacodyn Ther 1973;206:288–298.PubMed, CAS, Web of Science® Times Cited: 67

Sakata T, Yoshimatsu H, Kurokawa M. Hypothalamic neuronal histamine: implications of its homeostatic control of energy metabolism. Nutrition 1997;13:403–411.

Kalucy RS. Drug-induced weight gain. Drugs 1980;19:268–278.

Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology