What Is Tachyphylaxis? A Close Look at Acute Drug Tolerance

Imagine your symptoms improve after starting a medication. But, suddenly, the medication seems to stop working. Did the pharmacy give you a different dose by mistake? Was this a bad batch of medication?

Although those issues are possible, what’s more likely is that you are experiencing tachyphylaxis. This means that a medication’s effects have suddenly decreased. But it’s different from physical dependence or tolerance.

Here, we’ll discuss why some medications can become less effective. We’ll also discuss some common examples of tachyphylaxis and how it can be treated or prevented.

What is tachyphylaxis?

Tachyphylaxis is a condition where people experience a sudden decrease in effectiveness after taking a medication. This change usually occurs very abruptly. When this happens, the medication stops working as well for them as it did before.

People experiencing tachyphylaxis may notice some of their symptoms returning. This is often one of the first signs of tachyphylaxis. Make sure to contact your healthcare provider right away if you notice this.

Examples of tachyphylaxis

Let’s first review some common examples of medications that may cause tachyphylaxis:

1. Nitrates for chest pain: Nitrates are a group of medications that treat a type of chest pain called angina. People taking nitrates at frequent intervals might not experience as much symptom relief. Taking a break from the medication can sometimes prevent the problem.

2. Hydralazine: Hydralazine is a medication that treats high blood pressure. It’s effective for lowering blood pressure when you first start it. But, for some people, it stops working as well after you’ve taken it for a while. This is one of the reasons hydralazine is not a first-choice medication for high blood pressure.

3. Oxymetazoline: Oxymetazoline (Afrin) is a nasal spray that treats nasal congestion. It can help relieve stuffiness for people dealing with a cold. But taking it for more than a few days in a row can cause tachyphylaxis and a return of congestion. Most people call this sudden worsening of symptoms rebound congestion.

Listed above are a few examples of tachyphylaxis. We’ll soon highlight some other common medications that cause tachyphylaxis.

Tachyphylaxis vs. tolerance

Tachyphylaxis and tolerance share some similarities. But there are some important differences between them.

Tachyphylaxis happens quickly. There are reports that it can occur after just a few doses. Taking a higher dose of the medication doesn’t always provide any additional benefits.

Tolerance occurs when medications don’t provide the same benefits as they once did. Tolerance usually occurs gradually after taking medications for a long time. It can also mean you need a higher dose of a medication to get the same effect as before.

Tolerance can cause some people to become dependent upon these medications and feel the need to continue taking them. People who develop tolerance to a medication or substance may also experience withdrawal symptoms when it’s stopped.

What causes tachyphylaxis?

There are a few possible causes for tachyphylaxis. But sometimes it’s not clear why a person develops it.

In many cases, medications attach to a protein called a receptor to create their effects. Tachyphylaxis can happen when receptors don’t react to a medication in the intended way. In some cases, the receptors become less sensitive to the medication. In other cases, the number of receptors decreases. This means there’s less places for medications to attach to in the body to create their effects.

Genetics can also play a role in tachyphylaxis. There are slight differences in how each person reacts to and breaks down medications. But these unique differences can sometimes lead to tachyphylaxis. This means some people may be at higher risk for developing tachyphylaxis to a medication than others.

Medications that cause tachyphylaxis

Different medications have been known to cause tachyphylaxis. In addition to those listed earlier, below are some more medications that commonly cause tachyphylaxis:

1. Antidepressants: Depression medications can become less effective over time for some people. Up to one-third of people taking antidepressants may experience tachyphylaxis. It’s most seen with selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs).

2. Certain eye drops: People using eye drops for eye redness or irritation can experience tachyphylaxis. These medications include over-the-counter eye drops with ingredients such as tetrahydrozoline (Visine AC) and naphazoline (Clear Eyes Redness Relief).

3. Albuterol inhalers: Albuterol (ProAir, Ventolin, Proventil) is used as a rescue inhaler to help people with lung conditions like asthma when they’re having trouble breathing. Some research suggests that people using albuterol inhalers may sometimes develop tachyphylaxis. But this doesn’t always happen.

4. Erectile dysfunction medication: Sildenafil (Viagra) has also been reported to cause tachyphylaxis. Occasionally, symptoms improved when people took a higher dose. But some people stopped taking sildenafil because it was no longer effective. However, some experts question whether sildenafil truly does cause tachyphylaxis. Not enough research has been done to confirm if this is why it stops working for some people.

This is not a complete list of all medications that can cause tachyphylaxis. Make sure to contact your healthcare provider if it seems like your medication has stopped working.

How is tachyphylaxis treated?

There are a few different ways that tachyphylaxis can be treated. Listed below are some recommendations that healthcare providers may consider:

• Prescribing a higher dose: Taking a higher dose of medication can sometimes be effective in treating tachyphylaxis. One example is seen with fluoxetine (Prozac). A small study found that giving a higher dose of fluoxetine improved symptoms when lower doses stopped working.

• Switching to a different medication: Changing your medication may sometimes be helpful. For example, a healthcare provider may recommend an alternative antidepressant that works differently from the medication that caused tachyphylaxis.  

• Adding a different medication: Combining your medication with another medication may help treat tachyphylaxis. For instance, taking hydralazine with isosorbide dinitrate (a type of nitrate) can help prevent nitrate tachyphylaxis.

• Using nonmedication treatments: Therapies that don’t involve medications can sometimes be helpful when medications become less effective. For example, cognitive behavioral therapy (CBT) may be recommended for people who have developed tachyphylaxis to antidepressants.

Can you prevent tachyphylaxis?

It’s not clear what the best way to prevent tachyphylaxis is. Some researchers believe that taking a “drug holiday” can help prevent tachyphylaxis. But a drug holiday isn’t something you should try without a healthcare provider’s OK.

For example, people taking erythromycin to help with gastroparesis can sometimes avoid tachyphylaxis by pausing their medication for a few weeks. Another example of a drug holiday is seen with nitrates. A “nitrate-free interval” (a period of time when nitrates aren’t taken) of 12 hours can help prevent tachyphylaxis.

But a drug holiday isn’t right for everyone. It can be risky or dangerous to stop certain medications. It’s very important to talk with a healthcare provider first to see if this is an appropriate option for you.

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Written by:

Kevin Le, PharmD, BCPS, BCPPS

Kevin Le, PharmD, BCPS, BCPPS is a clinical pharmacy specialist in solid organ transplant at Ann & Robert H. Lurie Children’s Hospital of Chicago. He has been working as a pediatric pharmacist since 2016.

Edited by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

Reviewed by:

Katie E. Golden, MD

Katie E. Golden, MD, is a board-certified emergency medicine physician and a medical editor at GoodRx.

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