Benzodiazepines, Antihistamines, and Hypnotics: Short-Term Relief, Long-Term Risks

Lorrie Smith-Esterle, DNP, PMHNP-BC

Kentucky Psychiatric Care, PLLC

Medications such as Ativan (lorazepam), Xanax (alprazolam), Valium (diazepam), and Klonopin (clonazepam) are commonly prescribed for anxiety and sleep difficulties. Many people also use over-the-counter (OTC) sleep aids, including Benadryl (diphenhydramine) and products like ZzzQuil®, NyQuil®, and Unisom® SleepGels, which contain diphenhydramine. Prescription non-benzodiazepine hypnotics, often called “Z-drugs,” such as Ambien (zolpidem), Lunesta (eszopiclone), and Sonata (zaleplon) are also frequently used for insomnia.

Hydroxyzine, a prescription antihistamine, is sometimes used for anxiety or sleep.

These medications can be effective in the short term, but regular or long-term use carries important risks—particularly related to cognition, balance, and safety. Understanding both benefits and risks is essential when considering ongoing treatment.

✅ Potential Benefits of Short-Term Use

When used briefly and for appropriate indications, these medications may:

• Rapidly reduce acute anxiety or panic symptoms

• Help initiate or maintain sleep

• Provide temporary relief during periods of significant stress or short-term insomnia

Short-term use may be appropriate for situational anxiety, acute insomnia, alcohol withdrawal, seizures, or other time-limited conditions [1–3].

⚠️ Risks of Long-Term or Regular Use

With continued use, benefits often diminish while risks increase.

Cognitive, Balance, and Fall Risks

Benzodiazepines, sedating antihistamines, and hypnotics can all cause:

• Memory and concentration problems

• Slower reaction time

• Daytime sedation or “hangover” effects

• Impaired coordination and balance

  
  

These effects increase the risk of falls, fractures, and motor vehicle accidents, particularly in older adults and when taken at night.

Older adults taking benzodiazepines have:

• Nearly 5× higher risk of cognitive impairment

• More than double the risk of falls

• A 34% increased risk of hip fracture [1,2]

  
  

🧠 Antihistamines and Hypnotics Are Not Risk-Free

Products such as Benadryl®, ZzzQuil®, NyQuil®, and Unisom® SleepGels contain diphenhydramine, which has strong anticholinergic effects. Regular or long-term use has been associated with confusion, worsening memory, and increased risk of delirium and cognitive decline in older adults.

For this reason, diphenhydramine appears on the Beers Criteria, a set of guidelines developed by the American Geriatrics Society to identify medications that may pose more risk than benefit in adults age 65 and older. Medications on this list are linked to higher rates of confusion, excessive sedation, and falls. Being listed does not mean a medication should never be used, but it signals the need for extra caution, short-term use, and regular reassessment.

Hydroxyzine, while sometimes perceived as safer, can also cause sedation, dizziness, and impaired coordination—especially with regular use.

🌙 Non-Benzodiazepine Hypnotics (“Z-Drugs”)

Medications such as Ambien®, Lunesta®, and Sonata® were developed as alternatives to benzodiazepines but act on similar brain receptors.

Potential risks include:

• Next-day sedation and impaired alertness

• Memory problems or confusion

• Increased risk of falls and accidents

• Unusual sleep behaviors (such as sleep-walking or sleep-driving)

  
  

Risks increase with ongoing use, higher doses, and in older adults.

🔄 Dependence and Withdrawal

With ongoing benzodiazepine use, physical dependence is expected. Although Z-drugs carry a lower risk of dependence, tolerance and withdrawal symptoms can still occur, particularly with prolonged use.

Abrupt discontinuation of benzodiazepines—and sometimes hypnotics—can cause:

• Rebound anxiety or insomnia

• Agitation or tremors

• In rare cases, seizures [1,2]

  
  

Discontinuation should involve a gradual, supervised taper guided by a healthcare provider.

🌿 Alternative Treatment Options for Anxiety and Sleep

For many patients, non-sedating and non-habit-forming treatments provide safer and more effective long-term relief.

Evidence-based options include:

• Cognitive Behavioral Therapy (CBT) – A first-line treatment for anxiety that helps patients identify and change unhelpful thought patterns and behaviors, with durable benefits and no medication-related risks

• Cognitive Behavioral Therapy for Insomnia (CBT-I) – The first-line treatment for chronic insomnia, shown to be as effective as sleep medications short term and more effective long term

• SSRIs (e.g., sertraline, escitalopram) – First-line medications for chronic anxiety disorders [3,4]

• SNRIs (e.g., venlafaxine, duloxetine) – Helpful when anxiety includes physical symptoms such as muscle tension or restlessness [3,4]

• Beta blockers (e.g., propranolol) – Useful for situational or performance-related anxiety by reducing physical symptoms such as tremor and palpitations

  
  

These approaches are often used alone or in combination and may reduce or eliminate the need for long-term sedating medications.

💡 Bottom Line

Benzodiazepines, sedating antihistamines, and hypnotic sleep medications can provide short-term relief for anxiety or insomnia, but they are not ideal long-term treatments. With continued use, risks to cognition, balance, and overall safety often outweigh the benefits.

If you are using these medications regularly—or considering them—it is important to review their risks and benefits with your healthcare provider and discuss safer, long-term strategies when appropriate.

Lorrie Smith-Esterle, DNP, PMHNP-BC

Kentucky Psychiatric Care, PLLC

References

1. Brunner E, Chen CY, Klein T, et al. The Joint Clinical Practice Guideline on Benzodiazepine Tapering: Considerations When Benzodiazepine Risks Outweigh Benefits. American College of Medical Toxicology. 2024.

2. Brunner E, Chen CY, Klein T, et al. The Joint Clinical Practice Guideline on Benzodiazepine Tapering. American Society of Addiction Medicine. 2025.

3. Dubovsky SL, Marshall D. Benzodiazepines remain important therapeutic options in psychiatric practice. Psychother Psychosom. 2022;91(5):307–334.

4. Robertson S, Peacock EE, Scott R. Benzodiazepine Use Disorder: Common Questions and Answers. American Family Physician. 2023.