How Antihistamines Impact Mental Health

  • Apr 16th 2025
  • Est. 9 minutes read

Antihistamines block histamine receptors to reduce allergic reactions such as hay fever, hives, and anaphylaxis. They also affect brain function and mental health in potentially helpful and harmful ways. Some antihistamines can interact with the brain, affecting mood, cognition, and sleep. Recent studies have explored the benefits and risks associated with their effects on the central nervous system (CNS), as experts study their therapeutic benefits and risks in psychiatric care.

All About Antihistamines

Antihistamines are drugs that inhibit histamine receptors, reducing allergic and inflammatory responses. They are classified into two main types: H1 and H2 receptor blockers. H1 blockers, such as diphenhydramine and hydroxyzine, are primarily used for allergies, motion sickness, and sedation, whereas H2 blockers like ranitidine and famotidine reduce stomach acid or are used to treat ulcers [1]

Some antihistamines can make you feel drowsy, while others don’t. That’s because older, first-generation antihistamines (H1 blockers) can reach the brain and affect the CNS, often causing sedation. Newer, second-generation antihistamines (H2 blockers) are made to stay out of the brain, so they’re less likely to make you sleepy [1]. For people with mental health conditions, doctors must choose the right type of treatment. Depending on how they work in the body, these medications can also act as an antiemetic, reducing nausea and vomiting in some patients.  

Your Brain on Antihistamines

Antihistamines that cross the blood-brain barrier influence brain function by blocking histamine receptors, which can lead to sedation and cognitive changes. While a prescription for antihistamines is typically not needed, proceed with caution when taking them since their effects on the brain can vary significantly due to individual body chemistry and how they interact with other medications.

First-generation antihistamines have noticeable effects on the CNS. These medications cross the blood-brain barrier and affect neurotransmitters that regulate alertness, memory, and overall cognitive function. The resulting sedation may help with acute anxiety or insomnia, but long-term use raises concerns regarding slowed neural responses and potential memory impairment.

Antihistamines alter neural signaling pathways, which are central to understanding their impact on both physical and mental health. Some allergy medications may negatively affect brain health and raise the risk of developing dementia [2]. Clinicians report anecdotal evidence of “brain fog” and reduced mental sharpness with extended use. Though antihistamines can typically be purchased over the counter, it’s imperative to know the complex interplay between antihistamines and brain chemistry. 

Risks & Side Effects 

The risks and side effects of antihistamine use vary depending on how (and how often) they are used. Though many antihistamines are over-the-counter medications, they are to be taken with care and caution.  

People who rely on these medications for sleep or anxiety management, for example, may face challenges with motor coordination, attention, and overall brain health, especially with overuse. While antihistamines can provide immediate symptomatic relief, long-term usage can cause neurological damage. 

In addition to inducing sleep, which can lead to dependency, some antihistamines act as stimulants. The side effects of stimulants can cause dangerous physical symptoms that could become life-threatening if left unchecked. After taking an antihistamine, be on the alert for side effects, which may include: 

  • Sudden increase in heart rate or blood pressure
  • Dizziness, agitation, and persistent restlessness 
  • Cognitive Impairment: Memory loss, reduced concentration, and difficulty with problem-solving
  • Sedation: Excessive drowsiness that may affect daily functioning
  • Mood Disturbances: Potential increases in anxiety or depressive symptoms
  • “Brain Fog”: A persistent feeling of mental sluggishness and reduced alertness

Prolonged exposure to first-generation antihistamines may lead to subtle yet cumulative declines in cognitive function, which are difficult to reverse once established [3]. The mental health side effects of using antihistamines can be debilitating and lead to drug dependency. Dependence on antihistamines for sleep or anxiety relief can also contribute to withdrawal symptoms, such as irritability and rebound insomnia when discontinued abruptly. Awareness of these potential risks is vital for ensuring safe and responsible use. 

Antihistamines in Psychiatric Care

Antihistamines have found a niche in psychiatric practice, particularly as adjunctive treatments. In addition to helping reduce anxiety, certain antihistamines show potential in mood modulation. Early research suggests that by affecting serotonin and dopamine pathways, these drugs may offer benefits in managing depressive symptoms [4]. However, clinical data remains preliminary, and further studies are necessary to validate these applications. 

There is also ongoing research into the role of antihistamines in managing withdrawal symptoms in substance abuse treatments [5]. By alleviating anxiety and agitation during detoxification, these drugs might serve as supportive agents in medication-assisted therapies. The dual role of these medications in managing both anxiety and depressive symptoms presents a promising, albeit cautious, alternative in psychiatric care. 

However, integrating antihistamines into broader therapy regimens requires careful consideration and evidence-based strategies. Effective therapy involves not only addressing immediate symptoms but also ensuring long-term mental wellness. In clinical settings, for example, antihistamines are sometimes combined with cognitive-behavioral interventions to treat conditions such as insomnia and anxiety. This combination can provide rapid relief while concurrently teaching patients coping strategies to manage symptoms without over-reliance on medication. 

Mental Health Treatments

Antihistamines are finding their place in mental health treatment, with surprising benefits for several common psychiatric conditions. These medications work on both histamine and other brain chemicals, giving healthcare providers more options when standard psychiatric drugs aren’t effective or cause too many side effects.

Anxiety and Insomnia

Hydroxyzine is the most studied antihistamine for anxiety and the only antihistamine that is FDA-approved for use in anxiety [4]. Hydroxyzine is frequently prescribed for anxiety due to its calming effects, and some patients experience rapid anxiety relief [5]. It is considered a non-addictive alternative to benzodiazepines. Diphenhydramine is often used as a sleep aid or to combat insomnia, but long-term use is not recommended as it may impair cognitive function. Over time, some patients develop a tolerance to diphenhydramine, making it a short-term fix, not a long-term solution.

Depression

There is an established connection between antihistamines and antidepressants, emphasizing how the two have been linked in both historical and clinical contexts [6]. Researchers are exploring how histamine receptors can be used as new targets for antidepressant therapy [7]. Such advancements could offer effective mood regulation while minimizing cognitive risks. Early trials indicate that refining receptor selectivity may lead to effective and safer drugs for long-term use.

Psychotic Disorders

Histamine interacts with dopamine, which plays a critical role in psychiatric conditions such as schizophrenia and bipolar disorder. Some antipsychotic medications, like quetiapine, have antihistaminergic properties that help reduce symptoms like restlessness and agitation. When patients experience restlessness or agitation while on antipsychotic drugs, the addition of a low-dose antihistamine can help reduce side effects such as insomnia and anxiety, contributing to an improved quality of life [8]

Dependency & Misuse

Although antihistamines are generally not considered addictive, their sedative properties can lead to misuse. Overuse of antihistamines for sleep can result in tolerance and reduced effectiveness, while recreational use at high doses may lead to hallucinations. Usage patterns must be monitored to prevent dependency, as self-medicating beyond recommended doses to achieve a calming effect can result in withdrawal symptoms when stopped. 

Detoxing from stimulants or medications like antihistamines should always be done under medical supervision. The following approaches can support a safe and effective recovery process:

  • Gradual Dose Reduction: Tapering off the medication slowly helps minimize withdrawal symptoms and reduces the risk of relapse.
  • Stay Hydrated and Nourished: Drinking plenty of water and eating a well-balanced diet supports your body’s natural detox systems.
  • Incorporate Gentle Exercise: Physical activity can boost mood and energy levels while helping your body recover.
  • Use Behavioral Support: Cognitive-behavioral therapy (CBT) is effective for managing cravings, anxiety, and emotional triggers.
  • Consider Additional Support: In some cases, medication-assisted treatment (MAT) or inpatient care may be recommended to provide structure and round-the-clock support during detox.

These strategies help manage both physical and psychological dependencies. Overcoming addiction through therapy involves a combination of behavioral interventions and support systems. Support groups like 12-step programs offer peer encouragement and can be highly effective. Medication-assisted treatment (MAT) can also help stabilize brain chemistry during recovery. All of these approaches to therapy provide coping strategies to manage stress and prevent relapse from antihistamine misuse or abuse, ensuring long-term recovery success. 

Safe Antihistamine Use 

Use caution and adhere to the following guidelines to minimize risks and lessen the chance of side effects or misuse:

  1. Use Only When Necessary: Avoid daily reliance
  2. Follow Dosage Instructions: Do not exceed recommended doses
  3. Monitor Side Effects: Watch for cognitive issues
  4. Consult a Doctor: Before using it for mental health conditions
  5. Avoid Long-Term Use: Especially for sleep disorders 

Using antihistamines safely is key to maximizing benefits while minimizing risks. When used correctly, antihistamines like Hydroxyzine can help reduce anxiety and improve sleep. Still, they must be taken exactly as prescribed and not relied on for long-term treatment without professional guidance. Understanding these safe practices can empower you to use antihistamines effectively as part of a comprehensive approach to mental health.

Key Takeaways for Antihistamine Use 

The use of antihistamines in mental health presents a complex picture, balancing promising benefits with notable risks. While these medications can provide rapid relief for conditions such as anxiety and insomnia, their long-term impact on cognitive function demands cautious application. Healthcare providers must remain vigilant, employ safe use protocols, and monitor patient outcomes closely.

Understanding the benefits and potential side effects is essential for making informed decisions about their use. With proper guidelines and regular monitoring, these medications can be safely integrated into treatment plans to improve daily functioning and overall well-being. 

As research continues, the integration of antihistamines into psychiatric care may evolve, offering more refined and targeted therapies. Ultimately, the decision to use these drugs should be made collaboratively between patients and clinicians, ensuring that treatment plans are effective and safe. Before taking antihistamines, explore treatment options with a trained mental health professional.

References
    1. Farzam, K, Sabir, S, & O’Rourke, M.C. (2023). Antihistamines. StatPearls Publishing. National Library of Medicine (NLM). https://www.ncbi.nlm.nih.gov/books/NBK538188/. Accessed April 10, 2025.
    2. Alzheimer’s Drug Discovery Foundation. (n.d.). Can allergy medications harm your brain? Alzheimer’s Drug Discovery Foundation. https://www.alzdiscovery.org/cognitive-vitality/blog/can-allergy-medications-harm-your-brain. Accessed April 10, 2025.
    3. Litke, R., Garcharna, L. C., Jiwani, S., & Neugroschl, J. (2021). Modifiable risk factors in Alzheimer’s disease and related dementias: A review. Clinical Therapeutics, 43(6), 953-969. https://doi.org/10.1016/j.clinthera.2021.03.023. Accessed April 10, 2025.
    4. Garakani, A., Murrough, J. W., Freire, R. C., Thom, R. P., Larkin, K., Buono, F. D., & Iosifescu, D. V. (2020). Pharmacotherapy of anxiety disorders: Current and emerging treatment options. Frontiers in Psychiatry, 11, 595584. https://doi.org/10.3389/fpsyt.2020.595584. Accessed April 10, 2025.
    5. Davis, J. M., & Kahn, R. S. (1968). Hydroxyzine in the treatment of acute alcohol withdrawal. The American Journal of Psychiatry, 125(12), 1640-1644. https://psychiatryonline.org/doi/10.1176/ajp.125.12.1640. Accessed April 10, 2025.
    6. Block Center. (n.d.). Depression: Antidepressants were the first antihistamines. Block Center. https://blockcenter.com/depression-antidepressants-antihistamines/. Accessed April 10, 2025.
    7. Kriz, M., Vales, K., & Micale, V. (2021). Histamine system as a target for antidepressant drug development: A review of preclinical and clinical studies. Frontiers in Pharmacology, 12, 685740. https://pmc.ncbi.nlm.nih.gov/articles/PMC9537353/. Accessed April 10, 2025.
    8. Hede, V., & Devillé, C. (2019). Treating psychiatric symptoms and disorders with non-psychotropic medications. Dialogues in Clinical Neuroscience, 21(2), 193. https://pmc.ncbi.nlm.nih.gov/articles/PMC6787535. Accessed April 10, 2025.

 

Author Krista-Lynn Landolfi Writer

Krista-Lynn Landolfi is a health writer and certified Mindfulness-Based Stress Reduction (MBSR) teacher with over 20 years of experience.

Published: Apr 16th 2025, Last updated: Apr 28th 2025

Medical Reviewer Dr. Shivani Kharod, Ph.D. Ph.D.

Dr. Shivani Kharod, PhD, is a medical reviewer with over 10 years of experience ensuring health content is accurate and accessible.

Content reviewed by a medical professional. Last reviewed: Apr 16th 2025
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