Antidepressants and anti-anxiety medications can be life-changing treatments for millions of people.1 However, they can have unexpected and potentially risky interactions with other drugs.1,2 Has your doctor prescribed you multiple treatments to help you manage your medical conditions? Is one of your treatments an antidepressant or antianxiety medication? If you’ve answered yes to these questions and you take a prescription opioid, be proactive. Protect yourself by learning more about medication safety with antidepressants, antianxiety medications and prescription opioids.2

The stress associated with the COVID-19 pandemic

The COVID-19 pandemic and resulting lockdown had a significant emotional and physical strain on millions of people worldwide.3 At some point during the last year, almost all of us have been worried about our own health and that of our loved ones. Many of us have suffered additional stress as a result of isolation, economic hardship, and/or lifestyle disruptions. All of these factors have taken a huge toll on our collective well being.3

The increase in antidepressant and anti-anxiety medication prescribing

After a 3-year period of consistent decline, there was an increase in antidepressant and antianxiety medication prescribing last year.4 The trend is not surprising, especially when you consider the events of 2020. FDA-approved antidepressants and antianxiety medications have been shown to be effective treatments for the conditions for which they are indicated.1 However, some of these medications can interact with other drugs, and you should know the risks.2

The risks of combining medications with prescription opioids

Prescription opioid medications have been carefully studied and represent an important option for certain types of pain.5 However, it is important to keep in mind that the use of prescription opioids, whether prescribed for acute pain or chronic pain, is not without risk.6 When used alone, prescription opioids have potential side effects including nausea, vomiting, constipation, drowsiness and slowed breathing.7 When prescription opioids are taken at the same time as certain other medications, some of these side effects can intensify.6

Why combining medications can be risky

When you combine certain medications, there is a risk of an accidental opioid overdose situation—even if the medications are taken in their prescribed amounts.2 Dipenhydramine, a common ingredient in over-the-counter (OTC) cold and allergy medicines, for example, can have sedative-like effects.2 These effects can be problematic when combined with a prescription opioid’s sedative side effects.2 Certain antidepressant and antianxiety medications have the potential to interact with prescription opioids in this way as well.1 Examples of these antidepressant and antianxiety medications include:2,8

  • Benzodiazepine anti-anxiety medications like diazepam (Valium®), lorazepam (Ativan), alprazolam (Xanax®) and clonazepam (Klonopin)
  • Certain antidepressants like paroxetine (Paxil®, Paxil CR®), fluoxetine (Prozac), sertraline (Zoloft®), citalopram (Celexa), escitalopram (Lexapro), venlafaxine (Effexor XR®), desvenlafaxine (Pristiq®), amitriptyline and others
  • Certain drugs for sleeping problems like zolpidem (Ambien®, Edluar, others), eszopliclone (Lunesta®) and zaleplon (Sonata)
  • Drugs used to treat psychiatric disorders like haloperidol (Haldol), clozapine (Clozaril®, Versacloz®), aripiprazole (Abilify®) and quetiapine (Seroquel®)

Signs of prescription opioid overdose

Prescription opioids can make a person very sleepy. Combining prescription opioids with certain other medications can intensify this effect, slowing down breathing and reducing the heart rate to levels that increase the risk of death.2 A prescription opioid overdose situation is not always obvious, but there are important signs you can watch for.2 Signs of prescription opioid overdose include:9

  • Tiny pupils that do not change size in response to bright light (pinpoint pupils)
  • A deep sleep from which the person cannot be awakened
  • Very slow breathing and/or heartbeat
  • An extremely pale face that may be clammy to the touch
  • Lips or fingernails that appear purple or blue
  • Gurgling or vomiting noises

Whether you see one or all of these symptoms, do not hesitate—treat it as a critical situation that needs an overdose reversal medication such as Kloxxado®.10, 11

How and when to use overdose reversal medication

If you suspect that your friend or loved one is experiencing an accidental prescription opioid overdose, use an overdose reversal medication like Kloxxado right away.9 The time you spend deciding whether or not overdose reversal medication is needed could literally be the difference between life and death. Overdose reversal medication is safe to use even if overdose is suspected and not necessarily confirmed, so don’t waste precious minutes deciding whether or not to use it.9 If you are a prescription opioid patient, be sure the people who live with you know the signs of prescription opioid overdose and how to give overdose reversal medication in an emergency. If you do not have overdose reversal medication in your home, ask your doctor or pharmacist how you can obtain it.

Talk with your doctor or pharmacist

Make sure your primary care doctor, your pharmacist and/or any other healthcare providers you interact with (ie, therapists, surgeons or other specialists) know everything you are taking, including OTC medicines and supplements. This is especially important if you are taking medicine for mental health and also happen to be taking prescription opioid pain medication. It is a good idea to get all of your prescriptions filled at the same pharmacy as well. Doing so may help the pharmacist catch and reduce the likelihood of risky drug interactions with prescription opioids. It could even save your life or the life of a loved one. If you have questions about any of the medicines you take, including prescription opioids, or you would like to learn more about Kloxxado®, be sure to talk with your doctor(s) or pharmacist.

Kloxxado® is a trademark of Hikma Pharmaceuticals USA Inc.

All other trademarks mentioned are the property of their respective owners.

Please see the full Prescribing Information and Medication Guide for Kloxxado® for complete product details.

NOTE: This article was not written by a medical professional and is not intended to substitute for the guidance of a physician. These are not Hikma’s recommendations, but rather facts and data collected from various reliable medical sources. For a full list of resources and their attributing links, see below.


    1. Mental Health Medications. National Institute of Mental Health website. Available at: Accessed June 27, 2021
    2. Opioids and other drugs: What to watch for. Mayo Clinic website. Available at: Accessed June 27, 2021.
    3. Coping with Stress. Centers for Disease Control and Prevention website. Available at: Accessed June 27, 2021.
    4. Hikma Internal Analysis. IQVIA: NPA Audit, USC3 = 43400 ANTIANXIETY. Accessed February 10, 2021.
    5. Preuss CV, Kalava A, King KC. Prescription of Controlled Substances: Benefits and Risks. February 17, 2021. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan–. PMID: 30726003.
    6. Prescription Opioids. Centers for Disease Control and Prevention website. Available at: Accessed June 27, 2021.
    7. Opioid Toxicity and Withdrawal. Merck Manual Professional Version website. Available at: Accessed June 27, 2021.
    8. FDA Drug Safety Communication: FDA warns about several safety issues with opioid pain medicines; requires label changes. US Food & Drug Administration website. Available at: Accessed June 27, 2021.
    9. Opioid Overdose. MedlinePlus website. Available at: Accessed June 27, 2021.
    10. Opioid Overdose. World Health Organization website. Available at:
      Accessed June 27, 2021.
    11. Kloxxado® (naloxone hydrochloride) nasal spray [prescribing information]. Columbus, OH: West-Ward Columbus, Inc.; 2020.