What antihistamines cause weight gain? A comprehensive guide

October 5, 2025 •

4 min read

Studies have shown a potential link between chronic use of certain antihistamines and weight gain, with one 2010 study finding that regular users of prescription antihistamines had a higher average weight than non-users. This article will explore what antihistamines cause weight gain, the mechanisms involved, and strategies to manage this side effect.

Quick Summary

Antihistamines can contribute to weight gain by increasing appetite and causing fatigue, affecting both first- and second-generation medications. This article examines which specific drugs carry this risk, how the mechanism works, and what management strategies or alternative treatments are available.

Key Points

Older Antihistamines: First-generation antihistamines like Benadryl (diphenhydramine) and Periactin (cyproheptadine) are more strongly associated with weight gain due to significant sedation and effects on appetite.
Newer Antihistamines: Some second-generation antihistamines, including Zyrtec (cetirizine) and Allegra (fexofenadine), have been linked to weight gain, especially with long-term use, though the risk is generally lower than older versions.
Mechanism of Action: Antihistamines can block H1 receptors in the brain, which normally help regulate appetite, potentially leading to increased hunger and calorie intake.
Secondary Factors: Drowsiness caused by sedating antihistamines can reduce physical activity levels, contributing to fewer calories burned and potential weight gain.
Lifestyle Management: Implementing healthy eating, regular exercise, and mindful snacking can help counteract the potential weight gain from antihistamine use.
Alternative Treatments: Consider options like loratadine (Claritin), nasal sprays (Flonase, Nasacort), or immunotherapy (allergy shots), which may have a lesser or no association with weight gain.

Understanding the link between antihistamines and weight gain

For many, antihistamines are a vital part of managing chronic allergies and other conditions. However, the potential for weight gain is a side effect that concerns some long-term users. The link is rooted in how histamine, a natural compound in the body, functions beyond its role in allergic reactions.

Histamine plays a role as a neurotransmitter in the brain, where it helps regulate important functions, including appetite and wakefulness. Specifically, histamine activity in the hypothalamus helps suppress hunger. When an antihistamine, especially a first-generation one, blocks the H1 histamine receptors in the brain, it can interrupt this signal, potentially leading to an increase in appetite and overeating.

In addition to stimulating appetite, many antihistamines, particularly the older, more sedating types, cause drowsiness. This fatigue can lead to decreased physical activity and lower energy expenditure throughout the day, further contributing to weight gain.

First-generation antihistamines most likely to cause weight gain

Older, first-generation antihistamines are more known for their sedating effects because they readily cross the blood-brain barrier and affect the central nervous system. This is a primary reason they are more strongly linked to weight gain than their newer counterparts.

Key first-generation antihistamines associated with weight gain include:

Cyproheptadine (Periactin): This antihistamine is a potent appetite stimulant and has been historically used to promote weight gain in underweight individuals.
Diphenhydramine (Benadryl): Due to its strong sedative properties, chronic use of Benadryl is linked to weight gain. The drowsiness it causes can significantly decrease daily activity.
Promethazine (Phenergan): Primarily used for nausea and motion sickness, this potent sedating antihistamine is also associated with increased appetite and weight gain.
Hydroxyzine (Vistaril): Often prescribed for anxiety or itching, hydroxyzine is another sedating antihistamine with a potential for weight gain.

Second-generation antihistamines and weight gain

Second-generation antihistamines were developed to reduce sedative side effects by not crossing the blood-brain barrier as effectively as their older relatives. However, some studies have still linked long-term use of these drugs to a potential for weight gain. The evidence is more mixed, and the risk appears lower, but it is not non-existent.

Cetirizine (Zyrtec): Studies, including one using data from the National Health and Nutrition Examination Survey (NHANES), have shown an association between long-term use of cetirizine and higher weight and BMI compared to non-users. Cetirizine can also cause some drowsiness in a portion of patients, though less than first-gen antihistamines.
Fexofenadine (Allegra): Also implicated in the 2010 NHANES study, long-term use of fexofenadine was associated with a higher BMI and waist circumference.
Desloratadine (Clarinex): As the active metabolite of loratadine, desloratadine has also been associated with potential weight gain in some research.
Loratadine (Claritin): While some studies suggest a link, others, including the Obesity Medicine Association, consider loratadine a better option for those concerned about weight gain because it is less likely to affect the appetite center in the brain.
Levocetirizine (Xyzal): Similar to cetirizine, its parent compound, levocetirizine has also been mentioned in studies exploring the link between antihistamines and weight gain.

Comparing antihistamines and their weight gain potential


Antihistamine Type	Examples (Generic & Brand)	Sedation Level	Potential for Weight Gain	Key Consideration
First-Generation	Diphenhydramine (Benadryl), Cyproheptadine (Periactin)	High	High (more likely)	Strong sedation and appetite stimulation; not recommended for long-term use if weight gain is a concern.
Second-Generation	Cetirizine (Zyrtec), Fexofenadine (Allegra)	Low to Moderate (e.g., Zyrtec)	Moderate (long-term use)	Generally better, but evidence suggests long-term use may still be correlated with weight gain.
Second-Generation	Loratadine (Claritin)	Low	Low (less likely)	Often recommended as an alternative for weight-conscious individuals due to lower CNS effects.

Strategies to mitigate weight gain with antihistamine use

If you require ongoing allergy relief and are concerned about weight gain, there are proactive steps you can take in consultation with your healthcare provider:

Discuss alternatives with your doctor. Your healthcare provider can help you weigh the benefits and risks of different medications and may suggest a different type or brand.
Focus on lifestyle modifications. Healthy eating and regular physical activity can help offset any potential weight gain, regardless of the medication you take.
Manage increased appetite mindfully. If you notice increased hunger, try drinking water first, as thirst is sometimes mistaken for hunger. Keep healthy, high-fiber snacks on hand to help you feel full longer.
Monitor your intake. A food diary can help you track your eating habits and identify patterns related to medication use.

Finding alternatives to oral antihistamines

In some cases, your doctor may suggest alternative treatment options that do not carry the same risk of weight gain associated with oral antihistamines.

Nasal corticosteroid sprays: Medications like fluticasone (Flonase) and triamcinolone (Nasacort) target inflammation in the nose directly and are not associated with weight gain.
Antihistamine nasal sprays: Sprays like azelastine (Astepro) can deliver antihistamine effects locally with less systemic absorption, reducing the risk of side effects like appetite increase.
Immunotherapy (allergy shots): This long-term treatment works by desensitizing your body to allergens and does not involve blocking histamine receptors, thus carrying no risk of medication-related weight gain.

Conclusion

While not everyone who takes an antihistamine will experience weight gain, certain medications have a higher potential for this side effect, particularly with long-term use. First-generation antihistamines like Benadryl and Periactin, and even some second-generation types like Zyrtec and Allegra, have been associated with weight gain through increased appetite and decreased energy expenditure. Options like Claritin and nasal sprays, as well as lifestyle changes and immunotherapy, can help mitigate this risk. It is important to have an open discussion with your healthcare provider to find the best allergy management strategy for your individual needs. For more details on the association between antihistamine use and weight, one can explore the findings of the 2010 study published in the journal Obesity.

Explore more research on the effects of antihistamines on obesity here.

Frequently Asked Questions

First-generation, sedating antihistamines like Benadryl (diphenhydramine) and Periactin (cyproheptadine) are most likely to cause weight gain due to their strong sedative effects and impact on appetite regulation.

Yes, while considered less sedating, long-term use of second-generation antihistamines like Zyrtec (cetirizine) and Allegra (fexofenadine) has been associated with higher weight and BMI in some studies.

The primary mechanisms include blocking H1 receptors in the brain, which can lead to increased appetite, and causing drowsiness, which reduces physical activity and calorie expenditure.

Yes, according to the Obesity Medicine Association and other experts, Claritin is a better choice for those concerned about weight gain because it has less of an effect on the appetite center of the brain compared to many other antihistamines.

Yes, alternatives include nasal corticosteroid sprays (like Flonase), antihistamine nasal sprays (like Astepro), and allergy shots (immunotherapy).

Weight gain from antihistamines is likely to occur with chronic use. If you stop the medication, you may be able to lose the weight, but this is not guaranteed and requires a discussion with your healthcare provider.

First-generation antihistamines are highly sedating and have a stronger link to weight gain. Second-generation antihistamines are generally less sedating, but long-term use can still be associated with weight changes, though often to a lesser degree.