Buprenorphine treatment:
Your guide to the building blocks of OUD medication

Precipitated withdrawal can occur when someone who is actively dependent on opioids takes an opioid agonist or partial agonist, like buprenorphine. As a partial agonist, buprenorphine binds to opioid receptors in the brain. If the person using buprenorphine already has other opioids in their system, the buprenorphine displaces them from the receptors and blocks them from binding again. If there are too many opioids displaced from the receptors at once, it can cause precipitated withdrawal.

During precipitated withdrawal, the patient experiences a sudden onset of intense withdrawal symptoms. The symptoms of precipitated withdrawal include both physical and psychological effects, such as:

- Sweating
- Diarrhea
- Bone and muscle pain
- High blood pressure
- Faster heart rate
- Anxiety
- Irritability
- Intense opioid cravings
- Restlessness

One study suggests that around 9% of patients using buprenorphine to treat OUD develop precipitated withdrawal. Patients who concurrently use benzodiazepine or are chronic users of fentanyl or methadone are at higher risk for buprenorphine precipitated opioid withdrawal. Before beginning treatment, a patient's care team will consider their history of opioid use and risk level to decrease the chances of them experiencing precipitated withdrawal. Educating patients and using proper induction protocols may also reduce the risk.

Patients using medications for addiction treatment (MAT) often wonder if they can continue using that medication during and after surgery. In the past, many doctors recommended that patients stop using buprenorphine for a short period before and after surgery, but this advice is now outdated. Doctors were worried that continuing to use buprenorphine after surgery could make it more challenging to manage post-surgical pain.

While it's true that patients generally should not mix buprenorphine with opioids for pain management, there are better options than momentarily discontinuing buprenorphine use around surgery. New research suggests that patients should continue using buprenorphine to manage their OUD even before and after surgery. Patients’ care teams and buprenorphine doctors should work with them to find alternate pain management strategies that do not pose as significant a risk to their OUD treatment. Non-opioid medications, like nonsteroidal anti-inflammatory agents (NSAIDs), can effectively treat mild to moderate pain, for example. Acupuncture or physical therapy might help some patients manage their pain. The goal is to balance the need for pain management in post-surgical patients with their ongoing OUD treatment.

Buprenorphine is used to treat pain, which is useful to patients who recently underwent surgery. Research shows that buprenorphine treats chronic pain. These pain-relieving qualities might help OUD patients using buprenorphine after surgery.

Over 1 billion adults worldwide have high blood pressure, which can lead to heart damage, stroke, and kidney failure, among other health issues. Many OUD patients who have high blood pressure worry about how buprenorphine will affect their condition and whether it's more dangerous for them.

The good news is that buprenorphine does not cause high blood pressure. There's a common misconception that it does because initial buprenorphine use is associated with a blood pressure spike.

However, the buprenorphine is not directly responsible for that spike. Rather, patients taking buprenorphine for the first time are often going through the peak of opioid withdrawal. The blood pressure spike is a symptom of withdrawal, not buprenorphine use.

Buprenorphine can cause low blood pressure, though. The medication slows down the central nervous system, which can lead to dizziness, drowsiness, and low blood pressure as side effects.

Before beginning buprenorphine treatment, OUD patients should consult their care teams about pre-existing high or low blood pressure. Patients should also inform their clinicians of the medications they use to manage those conditions, if any. Certain medications can have adverse interactions with buprenorphine, so it's essential to discuss all these factors with the care team.

Oral health is an often overlooked, yet essential part of a person's overall well-being. Over 40% of adults in the United States report experiencing some mouth pain in the last year. Because some versions of buprenorphine are sublingual medications, patients worried about their oral health may wonder whether taking the medication will cause or worsen dental problems.

Back in 2022, the FDA released a warning that patients using sublingual medications containing buprenorphine have experienced some dental issues. These issues include tooth decay, cavities, oral infections, and tooth loss. This warning led some people to mistakenly believe that all buprenorphine patients, or even a significant percentage, will experience oral health problems while using buprenorphine. That's not the case.

Millions of Americans use sublingual buprenorphine medications each year without reporting any dental pain or other dental concerns. The American Academy of Addiction Psychiatry (AAAP) and several other organizations of addiction professionals even wrote a letter calling on the FDA to retract its warning about buprenorphine and oral health issues because it could be misleading to vulnerable patients dealing with OUD.

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The benefits of taking buprenorphine to treat OUD outweigh the risks of dental problems. Patients taking sublingual buprenorphine drugs, like Suboxone, can reduce their risk further by following the proper technique for taking their medications and rinsing their mouths out with water afterward.

Generally, before using any new medications, you should discuss them with your doctor to ensure no adverse drug interactions. This also applies to over-the-counter medications, like acetaminophen and ibuprofen. Some medicines can react with others in the body, causing severe side effects. Patients starting buprenorphine treatment may wonder whether they will have to cut out other medications they take to avoid these drug interactions.

In many cases, patients can continue to use at least OTC medications while taking buprenorphine. For example, there are no known interactions between NSAIDs, like Advil® and Aleve®, and buprenorphine. Acetaminophen also has no known interactions with buprenorphine. However, sedating antihistamines, like Benadryl® and Dramamine®, can interact with buprenorphine to cause extreme drowsiness and a depressed central nervous system. Patients using buprenorphine should discuss using antihistamines with their provider prior to use during OUD treatment.

When starting buprenorphine treatment, patients should discuss any medications they currently use with their care teams. If they later want to start using an OTC medication while using buprenorphine, it's worth checking in with their care teams again. It is safer to get a healthcare professional's opinion before combining any medications, even OTC medications. If a certain OTC medication has a negative interaction with buprenorphine, the care team may be able to recommend an alternative or a non-medication way of addressing the symptoms.

Selecting the correct dosage is just as important as choosing the proper medication in terms of effectiveness, and the same is true for MAT providers. But how can the patients themselves know if their dosages are correct?

A variety of factors affect the ideal buprenorphine dosage for any given patient. These include the patient's history of opioid use, body composition, selected medication, and sensitivity to medications. The care team weighs all these factors and determines the best dosage level. In some cases, they may start a patient out at a lower dosage and work up to higher doses of buprenorphine. This is called an induction or titration.

If the patient's dosage is not high enough, they may experience adverse symptoms. These symptoms include:

- Opioid cravings
- Pain
- Sweating
- Tremors
- Nausea
- Vomiting
- Anxiety
- Abdominal cramps

Patients who notice these symptoms after starting buprenorphine treatment should contact their healthcare providers to adjust their dosage. The patient's care team will try to find the right dose while still being effective in treating their OUD. A dosage that's too low can lead to opioid withdrawal symptoms, while a dosage that's too high does not become any more effective due to the ceiling effect.

For the best results, patients should take their buprenorphine exactly as instructed by their clinicians. They should take the recommended dosage consistently at the specified time. But what happens if a patient misses a dose? The effect of missing a dose will vary significantly based on the type of buprenorphine the patient uses.

Most patients using Suboxone, for example, take the drug once daily. If a Suboxone patient misses one dose, that's generally fine since the medication stays in a person's system for around 36 to 48 hours.

A patient would have to miss multiple doses in a row to start experiencing opioid cravings or withdrawal symptoms because the Suboxone is no longer blocking opioid receptors in the brain. Similarly, a patient could generally miss a dose of another daily buprenorphine medication, like Zubsolv, without negative effects. However, it’s important to discuss any missed doses with a provider, as they’ll provide a plan of action which may include taking the dose as soon as you remember or waiting until the next dose is due.

Missing a dose of an extended-release buprenorphine medication, like Brixadi or Sublocade, would have more significant effects, so reach out to your clinician team to get scheduled for a dose ASAP. Patients must see a healthcare professional immediately to have these medications injected weekly or monthly. Because patients receive these medications less frequently, keeping their appointments is essential. Patients should consult their care teams before adjusting their medications in any way. Clinicians can advise patients on what to do if they miss several doses or want to change something about their buprenorphine treatment.

Dealing with OUD during pregnancy can make a challenging time that much more stressful and difficult. Unfortunately, the majority of pregnant women with OUD do not receive evidence-based medication treatment. Some pregnant women are under the misconception that they don't even have any OUD treatment options during pregnancy. That's not the case, and pregnant women deserve to know about the treatments available to them.

Pregnant women can safely use buprenorphine and other medications for addiction treatment throughout their pregnancies. Using buprenorphine to treat OUD can improve outcomes for the newborn as well as the mother. Infants born to mothers who received methadone treatment during pregnancy have similar health outcomes to babies who were not exposed to methadone in utero. And compared to babies exposed to methadone, newborns who were exposed to buprenorphine in utero had even more positive outcomes.

If a patient is already using buprenorphine or another OUD treatment medication when she becomes pregnant, she may safely continue treatment. Patients who are already pregnant when they begin OUD treatment can also safely use buprenorphine. After giving birth, the risk of an overdose increases. Maintaining OUD treatment during this period can help lower a patient's risk of overdose. Mothers pursuing OUD treatment can also safely breastfeed their babies as only a small amount of the medication will pass to the babies through breast milk.

Microdosing is the practice of taking small amounts of a drug to experience its positive effects while minimizing adverse side effects. It's typically associated with psychedelic drugs, but there's a growing trend of microdosing medication for OUD treatment known as the Bernese method.

In the Bernese method, patients gradually introduce buprenorphine to reduce the risk of sudden onset opioid withdrawal symptoms. Microdosing buprenorphine may make precipitated withdrawal less likely, which could, in turn, make OUD treatment more effective for some patients. Anecdotally, OUD patients discuss the Bernese method positively as an option that may work when other approaches have not.

More research into the Bernese method is necessary to determine whether it reduces the risk of precipitated withdrawal and is an effective OUD treatment method. The Bernese method might be especially useful for patients who frequently use fentanyl or who are switching between full agonist and partial agonist OUD treatment. Patients interested in using the Bernese method should discuss this with their care teams. The clinicians can work with the patient to determine an appropriate dosage for microdosing buprenorphine as part of their OUD treatment plan. Do not attempt to microdose buprenorphine without the supervision of a qualified care team.

There are several other options for buprenorphine medications beyond Suboxone and Subutex.

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Sublocade is a buprenorphine medication administered as an extended-release injectable. Eligible patients can get Sublocade injections once a month at buprenorphine clinics or wherever they receive OUD treatment. Only a trained medical professional can administer Sublocade, which may make this version of buprenorphine less convenient for some patients. OUD patients cannot take the medication home to administer themselves or purchase Sublocade in bulk.

Unlike Suboxone, Sublocade only has buprenorphine as an active ingredient. While medication costs vary depending on a patient's insurance coverage, Sublocade is often more expensive than other buprenorphine medications because it has no generic option. However, this medication is generally covered under insurance and can be an excellent option for patients who often forget to take oral doses of Suboxone or have a difficult time reaching a pharmacy.

Brixadi is another injectable OUD medication that only has buprenorphine as an active ingredient. When healthcare professionals inject Brixadi, it releases over an extended period. Patients can receive another Brixadi dose monthly or weekly, depending on their care teams' recommended dosage. Injectable buprenorphine medications like Sublocade and Brixadi may be best for patients who would struggle to consistently take Suboxone. Likewise, if patients prefer to have professional oversight when taking their buprenorphine medications, Brixadi or Sublocade are strong options for OUD treatment.

Zubsolv is similar to Suboxone in that they both contain buprenorphine and naloxone as active ingredients to treat OUD. Zubsolv is a sublingual tablet that the body can absorb very quickly to start reducing opioid cravings and minimizing withdrawal symptoms. At the same dosage, Zubsolv is slightly more potent than Suboxone. It’s important to remember that Zubsolv has no generic equivalent, which could lead to higher costs depending on patients’ insurance plans.