What is Diphenhydramine?
Diphenhydramine is a first-generation antihistamine widely available in over-the-counter (OTC) products like Benadryl, Tylenol PM, and ZzzQuil [1.5.3, 1.5.4]. While primarily developed to treat allergy symptoms, its most prominent side effect is sedation, leading many to use it as a short-term sleep aid [1.3.3, 1.10.3]. A study found that over 60% of patients with insomnia reported clinical improvement after two weeks of treatment with diphenhydramine [1.4.4]. However, its effectiveness as a sleep aid is often accompanied by undesirable consequences, most notably next-day fatigue [1.2.5].
The Science Behind Next-Day Drowsiness: The 'Hangover Effect'
So, can diphenhydramine make you tired the next day? Absolutely. This lingering grogginess is known as the "hangover effect" and can impair your vigilance, cognition, memory, and motor skills [1.2.1]. There are two main pharmacological reasons for this.
First, diphenhydramine has a relatively long half-life, which is the time it takes for your body to eliminate half of the drug. In adults, the half-life is approximately 9 hours (with a range of 7 to 12 hours) and can be even longer in elderly patients, at around 13.5 hours [1.3.2]. Because of this long half-life, a significant amount of the medication can still be in your system when you wake up, continuing to exert its sedative effects [1.7.3].
Second, diphenhydramine is a potent anticholinergic agent [1.9.4]. This means it blocks the action of acetylcholine, a neurotransmitter crucial for attention, learning, and short-term memory [1.8.1]. By interfering with acetylcholine, diphenhydramine not only induces sleep but can also lead to next-day confusion, dry mouth, blurred vision, and constipation [1.8.1, 1.10.4]. The American Academy of Sleep Medicine actually recommends against using diphenhydramine for insomnia due to these side effects and a lack of evidence for long-term efficacy [1.5.1].
Factors Influencing the 'Hangover Effect'
Several factors can influence the intensity and duration of next-day drowsiness:
- Dosage: Higher doses (above the recommended 25-50 mg for sleep) increase the likelihood of next-day side effects [1.3.3]. The FDA has warned that taking higher than recommended doses can lead to serious heart problems, seizures, and even coma [1.11.2].
- Timing: Taking the medication too close to your wake-up time doesn't allow your body enough time to metabolize it.
- Individual Metabolism: Age, liver function, and genetics play a role in how quickly your body processes the drug. Older adults are particularly susceptible because they metabolize the drug more slowly [1.3.1, 1.3.2].
- Tolerance: Interestingly, the body can build a tolerance to the sedative effects of diphenhydramine after just a few days of use, meaning it becomes less effective for sleep while still posing a risk for other side effects [1.8.4].
Comparison of OTC Sleep Aids
| Feature | Diphenhydramine (Benadryl, ZzzQuil) | Doxylamine (Unisom SleepTabs) | Melatonin | Valerian Root |
|---|---|---|---|---|
| Mechanism | First-generation antihistamine, anticholinergic [1.9.4] | First-generation antihistamine [1.5.3] | Hormone that regulates sleep-wake cycle [1.5.5] | Herbal supplement thought to interact with GABA receptors [1.5.1] |
| Next-Day Drowsiness | Common; has a "hangover effect" [1.2.1] | More likely to cause next-day drowsiness due to a longer half-life than diphenhydramine [1.6.2, 1.6.3] | Can occur, but generally considered mild [1.5.5] | Appears to have mild side effects [1.5.5] |
| Half-Life (Adults) | Approx. 3-9 hours [1.3.1] | Approx. 10 hours [1.6.2] | Short; quickly cleared from the body [1.5.1] | Not well-defined |
| AASM Recommendation | Not recommended for insomnia [1.5.1] | Not recommended for insomnia [1.5.4] | Not recommended for insomnia [1.5.1] | Not recommended for insomnia [1.5.1] |
Minimizing and Managing Next-Day Grogginess
While the best way to prevent a diphenhydramine hangover is to use safer alternatives, if you do experience next-day grogginess, some strategies may help your body process the medication faster:
- Stay Hydrated: Drinking plenty of water helps your kidneys flush out the medication [1.7.1].
- Light Exercise: Gentle physical activity can boost circulation and metabolism [1.7.1].
- Eat a Healthy Meal: Supporting your body's metabolism with nutritious food can help it process the drug [1.7.1].
- Avoid Alcohol: Combining diphenhydramine with alcohol intensifies drowsiness and increases risks [1.5.4, 1.7.4].
Safer Alternatives and Long-Term Considerations
The American Geriatric Society advises that older adults should generally avoid diphenhydramine due to its strong anticholinergic properties and increased risk of falls and confusion [1.10.1]. Long-term use in older adults has been associated with an increased risk of dementia [1.8.1, 1.8.4].
For occasional sleeplessness, consider these alternatives:
- Second-Generation Antihistamines: Medications like loratadine and cetirizine do not cross the blood-brain barrier as readily and are non-sedating, making them safer for allergies without the cognitive side effects [1.8.2].
- Melatonin: While its effectiveness can vary, melatonin is generally considered a safer option for short-term use to help regulate sleep patterns [1.5.2, 1.8.1].
- Cognitive Behavioral Therapy for Insomnia (CBT-I): This is a highly effective, medication-free treatment for chronic insomnia that addresses the behaviors and thought patterns contributing to sleep difficulties [1.5.2].
For more information on the risks of high doses, you can visit the FDA's safety communication page [1.11.2].
Conclusion
While diphenhydramine can be effective for inducing sleep in the short term, the answer to "Can diphenhydramine make you tired the next day?" is a clear yes. Its long half-life and anticholinergic properties often lead to a hangover effect that can impair your functioning. Due to these side effects and the risk of tolerance and long-term cognitive issues, especially in older adults, experts generally do not recommend it for treating insomnia [1.2.3, 1.5.1]. Exploring safer alternatives and behavioral strategies like CBT-I is a better approach for managing sleep problems.
