What sleep medication can be safely added to a regimen of Benadryl (diphenhydramine) and busPIRone (buspirone) for anxiety?

Discontinue Benadryl and Consider FDA-Approved Sleep Medications

You should stop using Benadryl (diphenhydramine) for sleep immediately, as it is explicitly not recommended for insomnia treatment, and instead consider FDA-approved options like eszopiclone, zolpidem, or temazepam. 1

Why Benadryl Should Be Discontinued

• The American Academy of Sleep Medicine explicitly recommends against diphenhydramine for treating insomnia, showing only an 8-minute reduction in sleep latency and 12-minute improvement in total sleep time compared to placebo—with no improvement in subjective sleep quality. 1
• Diphenhydramine provides minimal clinical benefit (mean improvement of 12 minutes total sleep time with confidence intervals ranging from 13 minutes worse to 38 minutes better). 1
• Antihistamines like Benadryl have poorly established efficacy for long-term insomnia treatment and carry risks of cognitive impairment, especially when combined with other CNS-active medications. 1

Recommended Sleep Medication Options

First-Line FDA-Approved Medications:

Eszopiclone (2-3 mg) is the strongest option, providing:

• 28-57 minutes longer total sleep time versus placebo 1
• 10-14 minutes reduction in wake after sleep onset 1
• Moderate-to-large improvement in sleep quality 1
• No short-term usage restriction 1

Zolpidem (10 mg) offers:

• 29 minutes longer total sleep time versus placebo 1
• 25 minutes reduction in wake after sleep onset 1
• Moderate improvement in sleep quality 1
• Caution: FDA requires lower doses (5 mg) due to next-morning impairment risk 1

Temazepam (15 mg) provides:

• 99 minutes longer total sleep time versus placebo (the largest improvement among all agents) 1
• Small improvement in sleep quality 1
• Short-to-intermediate acting benzodiazepine 1

Alternative Options:

Suvorexant for sleep maintenance:

• 16-28 minutes reduction in wake after sleep onset 1
• 10 minutes longer total sleep time 1

Low-dose doxepin (3-6 mg) for sleep maintenance:

• 14-30 minutes reduction in wake after sleep onset 1
• Small-to-moderate improvement in sleep quality 1

Critical Safety Considerations with Buspirone

• Buspirone does not have sedative or hypnotic effects and should not be expected to help with sleep. 2
• Buspirone lacks the hypnotic, anticonvulsant, and muscle relaxant properties of benzodiazepines. 3
• Combining multiple CNS-active medications (Benadryl + buspirone + new sleep medication) increases risk of additive CNS depression, cognitive impairment, and psychomotor effects. 1
• Buspirone requires 1-2 weeks to achieve anxiolytic effects, so it should be continued for anxiety management. 3, 4

Important Drug Interaction Warnings

• Avoid combining benzodiazepines with other CNS depressants due to additive psychomotor impairment and risk of tolerance/dependence. 1
• All sedative-hypnotics should be taken on an empty stomach to maximize effectiveness. 1
• Never combine sleep medications with alcohol or use multiple sedating agents simultaneously without clear medical justification. 1
• Allow appropriate sleep time (7-8 hours) before activities requiring alertness to minimize next-day impairment. 1

Practical Implementation Algorithm

1. Immediately discontinue diphenhydramine 1
2. Continue buspirone for anxiety management (it will not help sleep) 3, 2
3. Start with eszopiclone 2-3 mg at bedtime as the most effective option 1
4. If eszopiclone is unavailable or not tolerated, use zolpidem 5-10 mg (start with 5 mg due to FDA warnings) 1
5. For patients requiring longer-acting agents or with significant sleep maintenance issues, consider temazepam 15 mg 1
6. Use the lowest effective dose for the shortest duration possible 1
7. Reassess need for continued pharmacotherapy regularly 1

Common Pitfalls to Avoid

• Do not use trazodone as first-line therapy—it is explicitly not recommended by the American Academy of Sleep Medicine for insomnia, showing no improvement in sleep quality. 1, 5
• Do not use melatonin—it provides only 9 minutes reduction in sleep latency with small improvement in quality. 1
• Do not continue diphenhydramine thinking "something is better than nothing"—the evidence shows it doesn't work. 1
• Avoid benzodiazepines in elderly patients due to increased risk of cognitive impairment and falls. 1
• Do not abruptly discontinue benzodiazepines if already taking them—taper to avoid withdrawal symptoms. 1