Alcohol, Opioids, and Gabapentin: 10 Benzodiazepine Interactions to Watch For

Benzodiazepines are prescription medications that treat a variety of medical conditions. These include anxiety and panic disorder. Examples of benzodiazepines include alprazolam (Xanax), diazepam (Valium), and lorazepam (Ativan).

If you have been prescribed a benzodiazepine, there are a few things to be aware of. Benzodiazepines are controlled substances. This means they have the potential for dependence and misuse. Benzodiazepines also have some notable side effects and drug interactions to consider.

Many benzodiazepine interactions happen with other medications that have similar side effects. Other interactions happen when one medication affects the blood level of another medication. Below, we’ll discuss 10 benzodiazepine interactions. We’ll cover how they occur, what to watch for, and how to manage them.

1. Opioids

Opioids are prescription pain medications. Their use is typically reserved for pain that isn’t managed by nonopioid medications. Common opioids include oxycodone (Roxicodone, OxyContin), hydrocodone / acetaminophen, and tramadol (ConZip, Qdolo). Like benzodiazepines, opioids are controlled substances.

In most cases, it’s best to avoid combining opioids and benzodiazepines. Taking these medications together increases the risk of severe drowsiness and dizziness. This can make falls more likely. This is especially risky in older adults, who are more likely to experience injuries and disability from falls.

Additionally, taking both medications can increase your risk for overdose and death. In fact, all benzodiazepines and opioids have a boxed warning for the risk of overdose when combined. This is the most serious warning the FDA can assign to medications.

EXPERT PICKS: WHAT TO READ NEXT

• Benzodiazepine FAQs: Learn the basics about benzodiazepines, including how they work and how individual benzos compare.

• Benzodiazepine side effects: Learn about common benzodiazepine side effects, such as drowsiness and dizziness.

• Why should you avoid combining benzodiazepines and opioids? Avoiding this combination helps lower your risk of excessive drowsiness and overdose.

Research shows that up to 50% of overdose deaths from prescription opioids also involve benzodiazepines. In one study, the rate of overdose-related death was 10 times higher for people prescribed opioids and benzodiazepines than for those prescribed opioids alone.

In rare cases, your prescriber may recommend taking a benzodiazepine and an opioid. In this case, follow their instructions closely for how to take these medications. Taking them as recommended decreases your risk of overdose.

2. Alcohol

Alcohol has similar effects on the brain as benzodiazepines, including dizziness and drowsiness. Combining alcohol and benzodiazepines increases the risk of these side effects being severe. Even more seriously, confusion, trouble breathing, and worsening mental health can occur.

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For these reasons, you should avoid drinking alcohol while taking benzodiazepines. Because benzodiazepines and alcohol affect everyone differently, there’s no safe amount of alcohol to consume while taking them. Even 1 drink is risky.

Before starting a benzodiazepine, be honest with your prescriber about your alcohol use. If you drink alcohol, your prescriber may recommend a different medication. They can also help you safely reduce your alcohol intake.

3. Sleep medications, such as Ambien

Several over-the-counter (OTC) and prescription medications can be used to help you sleep. These medications can interact with benzodiazepines, causing excessive drowsiness and possibly slowed breathing. Examples of sleep medications that may interact with benzodiazepines include:

• OTC antihistamines, like diphenhydramine (ZzzQuil), and doxylamine (Unisom Sleep Tabs)

• Melatonin

• Ramelteon (Rozerem)

• Eszopiclone (Lunesta)

• Zaleplon (Sonata)

• Zolpidem (Ambien)

• Trazodone (used off-label for sleep)

• Doxepin (Silenor)

• Belsomra (suvorexant)

• Dayvigo (lemborexant)

It’s best to avoid taking benzodiazepines and sleep medications together. This is especially true if you’re prescribed a benzodiazepine to help with sleep. Taking too many sleep medications at night can lead to daytime drowsiness the next day, along with falls and injuries.

If you’re having problems with sleep, tell your healthcare team. There are other ways (aside from medications) to improve your sleep.

4. Seizure medications, such as gabapentin

Seizure medications help prevent and treat seizures. Some benzodiazepines can also be used to treat seizures in some cases. Taking benzodiazepines with certain seizure medications can increase your risk of severe drowsiness and dizziness.

Examples of seizure medications that can interact with benzodiazepines include:

• Gabapentin (Neurontin)

• Pregabalin (Lyrica)

• Topiramate (Topamax)

• Carbamazepine (Tegretol)

• Lamotrigine (Lamictal)

Additionally, seizure medications like Depakote (divalproex) can increase levels of certain benzodiazepines, such as diazepam. This increases your risk of side effects. On the other hand, carbamazepine can have the opposite effect on clonazepam (Klonopin) and alprazolam. It can reduce blood levels of these benzodiazepines, making them less effective.

But be sure to provide your healthcare team with a list of medications you take. They can check for drug interactions and tell you how to monitor for negative effects.

5. Antipsychotics, such as quetiapine

Antipsychotic medications treat mental health conditions such as bipolar disorder and schizophrenia. Both antipsychotics and benzodiazepines increase the risk of drowsiness and dizziness. They can also both cause low blood pressure. Falls and injuries can also be more likely. Antipsychotics that can interact with benzodiazepines include:

• Aripiprazole (Abilify)

• Olanzapine (Zyprexa)

• Quetiapine (Seroquel)

• Clozapine (Clozaril)

If you take an antipsychotic, it’s likely an important medication for managing your health. And it may not be one you can change. So your prescriber may recommend not taking benzodiazepines at all.

6. Muscle relaxers, such as baclofen

Muscle relaxers help relieve muscle pain and muscle spasms. And like benzodiazepines, they can have sedative-like effects on the brain. Combining the two types of medications can cause excessive drowsiness, dizziness, and poor coordination. Examples of muscle relaxers that can interact with benzodiazepines include:

• Baclofen

• Carisoprodol (Soma)

• Cyclobenzaprine (Amrix)

• Tizanidine (Zanaflex)

• Methocarbamol

In most cases, it’s safest to avoid benzodiazepines and muscle relaxers together. Instead of muscle relaxers, your prescriber may recommend pain relievers like nonsteroidal anti-inflammatory drugs (NSAIDs). Examples include ibuprofen (Advil, Motrin) and naproxen (Aleve, Naprosyn).

7. Some antidepressants, such as fluoxetine

Certain antidepressants can also affect the brain. These medications are used to treat conditions like depression and anxiety. But when combined with benzodiazepines, the risk of side effects like drowsiness and dizziness is higher.

Examples of antidepressants that can interact with benzodiazepines include:

• Selective serotonin reuptake inhibitors (SSRIs), such as sertraline (Zoloft)

• Tricyclic antidepressants, such as amitriptyline

• Mirtazapine (Remeron)

• Trazodone

Of note, some antidepressants can change the levels of certain benzodiazepines. For example, fluoxetine is an SSRI that can increase alprazolam levels. This may lead to more intense side effects.

Your prescriber can help you choose a safe combination if you need an antidepressant and a benzodiazepine. You can also ask them how to monitor for potential side effects.

8. Medications that affect benzodiazepine levels, such as ketoconazole

Some medications can affect levels of benzodiazepines in the body. Benzodiazepines are metabolized (broken down) in the liver. Medications that block liver enzymes can increase benzodiazepine levels in the body. This raises the risk of side effects. Examples include:

• Some antifungals, such as ketoconazole

• Ritonavir-containing medications, such as Paxlovid (nirmatrelvir / ritonavir)

• Antidepressants, such as fluoxetine

• Seizure medications, such as Depakote and valproic acid

• Antibiotics, such as clarithromycin

• Probenecid (Probalan)

Other medications enhance liver enzymes. This can lower the levels of benzodiazepines in the body and make them less effective. These medications include:

• Carbamazepine

• Rifampin

• Phenytoin (Dilantin, Phenytek)

Some of these interactions may not be avoidable, depending on your individual situation. So ask your healthcare team about possible benzodiazepine interactions and how to manage them.

9. Stimulants, such as Adderall

Prescription stimulants treat attention-deficit hyperactivity disorder and narcolepsy. Like benzodiazepines, they’re also controlled substances. Examples include Adderall (mixed amphetamine salts) and Vyvanse (lisdexamfetamine).

As with all controlled substances, stimulants and benzodiazepines can lead to dependence and misuse. Stimulants and benzodiazepines can also make each other less effective. For example, benzodiazepines calm your nerves, but stimulants increase alertness and jitteriness.

Ask your prescriber before taking a benzodiazepine and a stimulant at the same time.

10. Herbs and supplements, such as ashwagandha

Certain herbs and supplements can make you sleepy. Since benzodiazepines have the same effect, it’s not always a good idea to combine them. Examples include ashwagandha, valerian, and gamma-aminobutyric acid.

Combining these herbal supplements with benzodiazepines increases your risk of excessive drowsiness. So tell your healthcare team if you take any herbs or supplements before starting a benzodiazepine.

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Written by:

Austin Ulrich, PharmD, BCACP

Austin Ulrich, PharmD, BCACP, is a board-certified ambulatory care clinical pharmacist. In his early career, he provided direct patient care in a variety of settings, including hospital and community pharmacies, and in a primary care clinic as a clinical pharmacist.

Edited by:

Amy B. Gragnolati, PharmD, BCPS

Amy Gragnolati, PharmD, BCPS, is a pharmacy editor for GoodRx. Amy currently holds her pharmacist license in Georgia and California.

Reviewed by:

Soojin Jun, PharmD

Soojin has 10 years of experience in various pharmacy settings, from inpatient to outpatient settings, and population health in value-based healthcare models. She completed training in various areas of healthcare to ensure patient safety, from activism, geriatric pharmacy, medication safety, healthcare quality, patient safety, death and dying, and trauma-informed care.

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