Patients who choose to use Medications for Opioid Use Disorder (MOUD) for opioid addiction have a choice of medications. One type of MOUD involve the use of an “opioid agonist.” An opioid agonist binds to the same receptors in the brain that were activated by the drug of abuse, but in a safer and more controlled manner. These medications can reduce the symptoms of withdrawal and reduce cravings, allowing for a more gradual, controlled recovery process and reducing the risk of relapse. The two opioid agonists used in MOUD are methadone and buprenorphine. Another type of medication called an “opioid antagonist” is a newer form of treatment that will also be discussed. Naltrexone is the only opioid antagonist currently available for treatment.
How are Opioids Used to Treat Addiction?
Opioid drugs are not only illicit drugs of addiction. Opioid medications have many legitimate uses, including for the treatment of addiction.
There are many different types of opioids, from prescription pain medications to heroin to drugs used to treat addiction. However, all opioid drugs act in similar ways in the body. These similarities allow for the possibility of “cross-tolerance.” Treatment with methadone or buprenorphine takes advantage of these similarities among opioids to use safer, more controlled doses of a prescription opioid to “replace” the opioid on which a person was physically dependent. This helps to block withdrawal symptoms and reduce cravings for illicit drugs, which both help reduce the risk for relapse.
Sometimes patients and their families or friends wonder why doctors use drugs like buprenorphine or methadone to treat opioid addiction, since these medications are in the same family as heroin and other prescription narcotics. However, physician-prescribed buprenorphine and methadone are not just “substituting” one addiction for another. Addiction treatment uses longer-acting and safer medications to help overcome more dangerous opioid addictions. Many studies have shown that maintenance treatment with long-acting opioids like methadone or buprenorphine helps keep patients healthier, reduces criminal activity, and helps prevent drug-related diseases like HIV/AIDs and Hepatitis.
Methadone is one of the most common medicines used to treat opioid use disorder. Methadone is an opioid agonist that strongly activates opioid receptors in the brain preventing, withdrawal symptoms and cravings for illicit drugs.
Methadone can only be prescribed and dispensed in special methadone clinics. To help prevent abuse, doses can initially only be received through daily visits to these specific clinics, which can also provide drug testing. Once a patient is stabilized and his stopped using illicit drugs, they may be allowed to take home up to a week’s worth of medication.
Methadone treatment has several advantages:
- Methadone is the most well studied MOUD for opioid addiction, and has been around much longer than other treatments.
- Methadone treatment has the highest treatment retention rates of any other MOUD (80% of opioid-dependent patients remain in methadone treatment after 6 months).
- Methadone helps make withdrawal milder and more manageable.
- Methadone can be taken by mouth in a pill or liquid, avoiding continued use of needles. It can be taken only once a day.
- When carefully overseen by a doctor, methadone is safe to use.
Because methadone is a relatively strong opioid, methadone use also has several risks. Methadone use may cause cardiac arrhythmias (changes in heart rhythm). Fatal methadone overdoses are also possible. Combination of methadone with benzodiazepine abuse increases risk of unintentional overdose. Since methadone has long-acting effects in the body, the medication builds up for up to five days of continued use. The daily maintenance dose must be carefully and slowly adjusted, and there is a risk of overdose if it is increased too fast.
Buprenorphine is a relatively new medication, approved in 2002 for the treatment of opioid addiction both during and after detoxification. It is also sometimes used in the hospital for pain relief after surgery and for chronic pain.
How does Buprenorphine work?
Like other opioid drugs, buprenorphine binds to “mu” opioid receptors in the brain. However, buprenorphine is only a “partial agonist” for these opioid receptors, and cannot stimulate the brain as strongly as other opioids. This allows buprenorphine to have a “ceiling effect.” When taken by mouth, it is rare for buprenorphine to stimulate opioid receptors strongly enough to cause fatal overdose.
Buprenorphine is also a long-acting medication, providing stable, low-level activation of opioid receptors in the brain, preventing withdrawal symptoms and cravings. Importantly, since buprenorphine is a partial agonist that binds tightly to the opioid receptors, it also blocks the effects of other opioids so that patients who use will not feel a drug effect.
Buprenorphine binds to opiate receptors in the brain. Source: National Institute on Drug Abuse. Obtained from https://www.drugabuse.gov/sites/default/files/imagecache/content_image_landscape/slide-18.gif
What is Buprenorphine treatment like?
Buprenorphine is most commonly given as a sublingual tablet, and dissolves under the tongue. It comes in two brand name forms that are also available as generic medications:
- Subutex: Buprenorphine alone
- Suboxone: Buprenorphine + Naloxone
There are also other branded formulations that are less commonly used, but are still available:
- Zubsolv: another formulation of Buprenorphine + Naloxone with different dosing
- Bunavail: Buprenorphine + Naloxone formation that adheres to your cheek and slowly dissolves
- Sublocade: Buprenorphine subcutaneous injection that lasts for 1 month and dissolves
How do patients start taking buprenorphine?
Doses of buprenorphine work best when they are given after symptoms of withdrawal have already started. Patients must wait 12-18 hours after their last use of a shorter-acting opioid drug, such as heroin or prescription painkiller. Buprenorphine can cause withdrawal if taken after a stronger dose of another opioid, as it can “kick out” and replace other opioids in the brain. However, after withdrawal has already started, beginning buprenorphine doses can then help to relieve withdrawal symptoms and prevent relapse.
Low-dose buprenorphine treatment has less patient retention than methadone treatment. However, higher doses of buprenorphine have similar levels of patient retention as methadone. High-dose buprenorphine and methadone patients also have similar rates of relapse and self-reported heroin use during treatment. Buprenorphine’s other advantages make it preferable for some patients:
Convenience and Flexibility of Buprenorphine
While methadone must be prescribed and distributed daily in special clinics, patients with prescriptions for buprenorphine do not need to visit special drug clinics to pick up their medication. Because buprenorphine is generally safer to use than methadone, certified physicians in a “regular” medical office can prescribe it.
Continuing Treatment with Buprenorphine
After their treatment plan is stable, patients will be required to see their physician for continued treatment at least every two to four weeks. If patients miss an appointment, they may not be able to refill their medication on time and experience uncomfortable withdrawal symptoms.
Opioid-dependent patients maintained with buprenorphine treatment may remain physically dependent on this opioid medication, but are not “addicted” if these medications are used only as help with the process of recovery. Withdrawal symptoms can still occur if more than one dose is missed.
What happens in buprenorphine patients’ regular visits to the doctor?
- The patient will be asked to bring the medication container to each visit.
- The prescriber will ask about the medication efficacy, side effects, and any other substance use. They will also ask questions about your general mood and well-being.
- The patient may also be asked to give urine, blood, or breath samples at the time of the visit.
- The patient may also sometimes be called in randomly to have his or her pills counted and/or to give a urine sample to test for the presence of other drugs and alcohol. This is a regular part of drug treatment, and helps keeps patients safe by preventing drug abuse.
Safety of Buprenorphine
Because of its “ceiling effect,” buprenorphine is much safer in the case of an overdose than other opioids. Buprenorphine is only a partial agonist of opioid receptors in the brain, and is less likely to suppress breathing to the point of death than opioids like heroin or methadone. Buprenorphine also has less risk of causing problems in heart rhythm. When treatment is stopped, buprenorphine causes milder withdrawal than methadone. Because buprenorphine is safer to use than methadone, it is easier to prescribe and doesn’t require visits to special methadone clinics.
Risks of Buprenorphine
However, Buprenorphine can still be dangerous when mixed with other drugs, and life-threatening overdose and death have occurred when it is not taken as recommended by a physician. Patients interested in buprenorphine should be aware of how to use this medication safely.
- It is important for anyone taking buprenorphine to make their entire medical team aware of their use of buprenorphine, even doctors not directly involved in their addiction treatment. Sharing this knowledge can help prevent dangerous prescription interactions.
- It is important not to use street drugs or excess alcohol with buprenorphine. These combinations can make life-threatening overdoses more likely. Patients need to tell their doctors about any other illicit drug use. Overdose deaths may occur when buprenorphine is injected against medical instructions in combination with benzodiazepines (Klonopin, Ativan, Halcion, Valium, Xanax, Serax, Librium, etc.).
- Buprenorphine should also be kept away from children, as life-threatening overdoses have occurred when children take this medicine.
What is the right dose of Buprenorphine?
After patients and their family members have dealt with opioid addiction, they may be concerned about buprenorphine’s potential for abuse, potentially substituting one “high” for another. The “right” dose of buprenorphine is one that allows the patient to feel and act normally. It may take anywhere from a few days to a few weeks to find the right dose. Every opioid can have stimulating or sedating effects, especially in the first weeks of treatment. Patients new to Suboxone may seem drowsy, stimulated, or restless. While their dose is being adjusted, patients may experience withdrawal, daytime sleepiness, or trouble sleeping at night. However, once a patient is stabilized on the correct dose of buprenorphine, the patient should not feel “high,” and there should be no excessive sleepiness or intoxication.
Family members can help keep track of these symptoms to help the doctor find the best dose for the patient. Once the right dose is found, it’s important to take the dose on time, daily.
What are the benefits of Suboxone (Buprenorphine + Naloxone)?
Suboxone, a formulation of buprenorphine that includes naloxone, is safer to use than buprenorphine alone. Suboxone has less risk of abuse through injection because of its extra ingredient, naloxone. Naloxone is not active when Suboxone is taken under the tongue as directed. When taken as directed, Suboxone can actively stimulate opioid receptors and prevent withdrawal symptoms. However, if Suboxone is abused and injected to attempt a bigger “high,” naloxone becomes active and blocks the body’s opioid receptors, causing withdrawal symptoms. This helps decrease the risk that Suboxone might be abused.
These unique safety features make Suboxone safer to prescribe and to use outside of strict inpatient or intensive clinic regulations. After stabilization, most patients are able to take home one to four weeks of Suboxone at a time.
Despite these safety features, Suboxone can be still be dangerous when it is mixed with other drugs (street drugs or certain prescription medications) or excess alcohol.
Buprenorphine Taper: Maintenance Vs. Detoxification
How long do patients need to take buprenorphine?
The optimum time for buprenorphine treatment isn’t yet clear. Buprenorphine has been shown to be very effective in helping patients with detoxification, but detoxification is only the first step in what can be a long and difficult road to recovery. Patients who choose to stop buprenorphine after detoxification should be aware that they are still at a very high risk for relapse over the next few months to years. Majority of patients relapse shortly after stopping buprenorphine maintenance of less than 6 months.
Many patients attempt to transition away from use of methadone or buprenorphine through a “tapering” process. A “taper” is a series of reductions in dose over a few weeks to months. However, relapse rates are very high for patients who taper off buprenorphine/naloxone.
Many studies have followed patients before and after being tapered off of buprenorphine/naloxone maintenance. A 2011 study found that patients that have been stabilized with buprenorphine/naloxone treatment often relapse after tapering off MOUD, even when therapies like counseling are continued. This study found that more than 90% of patients relapsed after an initial 3-week taper. After re-stabilization with MOUD for 12 weeks, over 90% of these patients relapsed again when tapered off buprenorphine/naloxone, even when they received additional counseling. Another study in 2009 followed patients who tapered off buprenorphine/naloxone after 4 weeks of maintenance treatment. At the end of a 7-day taper, less than half (44%) of patients were still opioid-free. When the tapering process was extended to 28 days, only 30% of patients were opioid-free at the end of the taper. Only 18% of patients were still completely abstinent from opioids 30 days after the taper ended. Thus, tapering from buprenorphine is associated with high rates of relapse. The optimum duration of buprenorphine treatment has not yet been determined, but tapering very slowly over 4 weeks is more successful than shorter tapers.
How can the tapering process be more effective?
Researchers are still working on ways to reduce the risk of relapse after tapering off of buprenorphine. When patients and their doctors decide to gradually reduce their dose of buprenorphine, studies have shown that a slow tapering process is a safer option in preventing relapse. There has been little research on the outcome of patients tapered off buprenorphine after longer periods of stabilization with MOUD. Some patients may choose to transition to long-acting injectable naltrexone (Vivitrol, described below) after tapering off buprenorphine, since this opioid blocker can prevent relapse to any opioid.
Is Suboxone (Buprenorphine+ Naloxone) Useful for Methadone Patients?
Because Suboxone treatment is safer and easier to use than methadone and does not require daily visits to methadone clinics, methadone patients may be interested in switching to buprenorphine. However, because buprenorphine is a partial agonist, a patient maintained on methadone may find buprenorphine to be a “weaker” medication. Methadone patients may go into major withdrawal if they switch from a full dose of methadone to buprenorphine.  To avoid withdrawal, a methadone patient would first have to reduce the methadone dose to 40 mg or less daily, often a difficult process with a high risk of relapse.
In some cases, buprenorphine may not be strong enough for patients used to high doses of methadone, and may lead to increased cravings and increased risk of relapse. Patients interesting in switching from methadone to buprenorphine should be aware of these risks and remain open to resuming methadone if necessary.
Persons currently addicted to prescriptions pain medications or heroin, as well as patients maintained with methadone, should not accept buprenorphine or Suboxone from a “friend,” as this medication will cause uncomfortable withdrawal symptoms. Always ask a physician before switching medications.
Naltrexone: Opioid Antagonist Therapy
Naltrexone is an alternative treatment for opioid addiction. Unlike methadone or buprenorphine, which are both opioid agonists (with opioid-like effects), naltrexone is an opioid antagonist– meaning that it blocks opioid receptors in the brain instead of activating them. By blocking opioid receptors in the brain, naltrexone can prevent all effects of any opioid drugs taken while naloxone remains in a person’s system. This treatment blocks everything from a “high” to an overdose. Besides the obvious safety benefits of naltrexone, this “blocking “ effect can also give an addicted person time to “unlearn” patterns that lead to cravings and habits related to opioid abuse. Patients who successfully transition to naltrexone use have much lower rates of relapse than patients who receive counseling alone.
Who is a candidate for Naltrexone treatment?
While agonist maintenance with buprenorphine or methadone remains the treatment of choice for opioid addiction, it does not work for everyone. Some patients do not like the idea of long-term use of opioid drugs. Long-term treatment with buprenorphine or methadone also remains controversial for the treatment of young people or for those with only a brief history of opioid addiction. Patients may also prefer naltrexone to agonist maintenance (buprenorphine or methadone) if they are highly motivated or are working in a profession in which agonist use is controversial. Patients who are interested in abstinence after trying agonist therapy may be good candidates for naltrexone. Abstinent patients that are at a high risk of relapse, such as those with acute or worsening psychiatric illness, may also benefit from naltrexone therapy.
Beginning Naltrexone Therapy
However, naltrexone treatment is more difficult to begin than other MOUD drugs. It can be difficult to transition from active opioid use to a first dose of naltrexone. Because naltrexone is a strong opioid receptor antagonist, it can “kick out” other opioids from the brain and cause withdrawal symptoms. A person who is physically dependent on opioids needs to be abstinent from heroin for 5-7 days, or abstinent from methadone for 7-10 days, in order to begin naltrexone treatment. The extended period of opioid abstinence required creates an “induction hurdle” for naltrexone, as compared to the 12-24 hours of abstinence required for buprenorphine or methadone. When naltrexone is begun under physician supervision, other medicines can be used make withdrawal less painful in the beginning stages of naltrexone treatment. Certain non-opioid “comfort” medicines to relieve withdrawal symptoms like muscle cramping, nausea, and insomnia. Some patients may need a higher level of support, such as an inpatient stay to begin naltrexone, if they have a more severe pattern of opioid use or a co-existing medical or psychiatric illness.
Vivitrol: Long-Acting Naltrexone
Naltrexone treatment has been difficult to use in the past. Before 2010, naltrexone was only available in the form of a once-daily pill, and it was often hard for patients to remember to take and keep up with their medication. The approval of a long-acting form of injectable naltrexone (Vivitrol) that only needs to be taken about once every month is much easier to maintain than the older oral form of naltrexone.
Risks of Naltrexone
Some dangers are associated with naltrexone use. Patients taking naltrexone have lost their tolerance to opioids, and will be at risk of accidental overdose if they drop out of treatment and stop taking naltrexone. This risk is also why the daily pill form of naltrexone is not recommended for maintenance use, as patients can more easily stop the medication and may overdose if they return to using. One advantage of the long-acting injectable naltrexone (Vivitrol) is that is wears off slowly, so that there is no sudden loss of opioid blockade, thus reducing the risk of overdose. It is expected that about half of naltrexone patients will “test” the effects of the drug by taking an opioid, but patients should not continue to use opioids during naltrexone treatment because of a greater risk of dropping out of therapy after treatment.
Naltrexone + Behavioral Therapy
Naltrexone therapy is more effective when combined with behavioral therapy that encourages lifestyle changes to support abstinence from opioids. Network Therapy (see later section), incentives for abstinence, and relapse prevention therapies may all benefit patients on naltrexone.
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