Buprenorphine: The Little Known Treatment Option
The United States is experiencing an epidemic of opioid overdose and addiction. One of the important changes that needs to be made in order to help combat this epidemic is increased access to effective, scientifically-proven, medication-assisted treatment. In my previous post I discussed what methadone is how it helps opioid addicts. But another treatment is also available but is not nearly as well known: buprenorphine.
As I discussed in my previous blog post, methadone is a long-acting mu opioid receptor (MOPR) agonist. All opioid drugs (heroin, morphine, oxycodone, methadone, etc.) activate the MOPR. However, methadone is different than the other opioids in that it activates the MOPR for an entire day (unlike heroin or oxycodone, which are short acting). This unique property of methadone allows it to not only block the withdrawal and drug craving but prevents heroin from causing a “high”. Methadone has been used for successfully keeping patients off of heroin for over 40 years.
Buprenorphine is a newer treatment that serves a similar purpose as methadone: it blocks the craving and withdrawal and allows the patient to live their daily life. However, buprenorphine has very different properties at the MOPR.
The Properties and Mechanism of Buprenorphine
Buprenorphine also acts on the MOPR but unlike methadone or heroin, it is a partial agonist with extremely high efficacy . These unique chemical properties mean:
1. buprenorphine activates the MOPR but not all the way, and
2. it sticks to the MOPR very tightly and for a long time.
The combination of these properties makes buprenorphine beneficial for treating opioid addiction because it can activate the MOPR and block the withdrawal symptoms and drug cravings that plague a heroin addict and can simultaneously and successfully block the “high” from heroin by not allowing heroin to activate the MOPR (same function as methadone).
Buprenorphine’s pharmacology and activity at the MOPR is truly unique. It’s so effective at binding to the MOPR that it can actually out compete other opioids . For example, let’s say someone just injected heroin and then a few hours later took a buprenorphine pill. The buprenorphine would kick the heroin off the MOPR, but not activate the MOPR fully due to its partial agonist ability, and effectively send the person into withdrawals. This is important to keep in mind that buprenorphine should never be given to patient unless they are already in withdrawals . Only when no other opioids are present can buprenorphine block the withdrawal symptoms.
A comprehensive review done by the Cochrane collaboration looked at 31 different studies with a total of 5,430 patients . This massive review concluded that both methadone and buprenorphine are effective at keeping patients in treatment and off of heroin. But while the basic functions of methadone and buprenorphine at treating opioid addiction are the same, there are many differences in the treatments and each has it’s own risks and benefits. I’ll return to the Cochrane study at the end of the post too for some follow-up discussion on its findings.
Methadone vs. Buprenorphine: Risks & Side Effects
1. Lowering breathing rate
Any opioid compound can lower breathing rate (this is one of the normal functions of the MOPR). In fact, deaths due to opioid overdoses usually occur because of this suppression in breathing rate (respiratory depression).
When starting treatment, both methadone and buprenorphine also run risk of overdose due to respiratory depression because you don’t know how the specific dose will affect the patient. A dose needs to be figured out that works for the individual patients but there is a risk that the initial dose will be too high or the patient will be too sensitive to that dose.
However, because of its partial agonist activity, buprenorphine has a maximum dose that it is effective (what’s a called a “ceiling”). This makes it a little bit safer than methadone because it may have a weaker affect on breathing rate and thus a lower risk for overdose. (I’ll talk more about this maximum dose for buprenorphine later).
3. Milder side effects?
Both methadone and buprenorphine (and all opioids) cause similar side-effects (sweating, constipation, sexual dysfunction, etc.) but buprenorphine’s appear to be milder side-effects than methadone for most patients .
4. Dependence and withdrawal
Unfortunately, both methadone and buprenorphine can produce dependence and withdrawal symptoms if they are not taken (the same happens with heroin too of course). While a patient can stay on methadone indefinitely without any real problems (see my previous post), it may be difficult to taper off of methadone.
Some studies suggest it might be easier to taper off of buprenorphine. While buprenorphine’s withdrawal symptoms are just as prolonged as methadone’s, they also appear to be a little less severe.
Methadone vs. Buprenorphine: Potential for Abuse
1. Opiate naïve dosing
If a person has never taken an opiate like oxycodone or heroin before and then takes methadone or buprenorphine, they will experience an opiate high. As such, both methadone and buprenorphine have a risk for being abused.
2. Dosing ceilings
But buprenorphine has a maximum dose at which it will produce a high (a “ceiling”). A person addicted to opioids will need to constantly increase dose because of tolerance that develops but with buprenorphine, they will reach a ceiling in which an increase in dose does not feel any different (a maximal effect at around 20mg) . This means that at a certain point, the buprenorphine will stop satisfying the high. In contrast, methadone has no dose ceiling and a person can escalate to high doses (as high as 120mg in some cases).
Unfortunately, the dose ceiling of buprenorphine also reduces its effectiveness at treating very heavily addicted heroin addicts (more about this later) and may not be able to satisfy the withdrawal symptoms or drug cravings in these patients.
3. Office prescriptions and ease of access
Another real fear with buprenorphine is that because it can be prescribed in an office setting, people will seek it out to abuse and inject it in much the same way that heroin is abused and injected. Indeed, studies have found that it is abused this way .
4. The addition of naloxone
To counter this potential for abuse, practically all buprenorphine used to treat opioid addiction is combined with another compound called naloxone. Naloxone is an MOPR antagonist, which means it blocks all activity at the MOPR. If buprenorphine/naloxone is taken orally (the way it’s supposed to be taken) than the naloxone is very quickly metabolized by the liver and does not interfere with the effectiveness of the buprenorphine.
But if buprenorphine/naloxone is ground up and injected, the naloxone will not be metabolized and will block the high feeling from the buprenorphine. The buprenorphine/naloxone formulation is actually quite effective and reducing the abuse of buprenorphine.
Methadone vs. Buprenorphine: Legal Status and Accessibility
This is probably the biggest difference between the two treatments. As I discussed previously, methadone is restricted to being administered by trained professionals at methadone clinics only. Take-home doses are only allowed after 2 years of compliance at the clinic. This is one of methadone’s biggest obstacles for successful treatment. The inconvenience of showing up at the clinic everyday is one of the reasons why some patients drop out of treatment.
The legal restrictions on buprenorphine are much less than on methadone. The Drug Addiction Treatment Act of 2000 (DATA 2000)i allowed physicians to become certified to prescribe buprenorphine in a clinical setting (i.e. a doctor’s office). DATA 2000 initially restricts doctors from prescribing buprenorphine to only 30 patients. But if the doctor has proven to be responsible and successful with prescribing buprenorphine for a year, he/she may apply for an increase to 100 patientsii.
Most people have never heard of buprenorphine so there are also fewer stigmas around it than methadone. Reducing stigma around a treatment is one way to retain a patient in treatment .
The legal restrictions on buprenorphine are still significant, even if they are less than the restrictions on methadone. On the other hand, opioid pain medications have far fewer legal restrictions than either treatment and no restrictions on the number of patients they can be prescribed to. Ironically, it is far easier to get a prescription for oxycodone, which can start you on the path to heroin addiction, than it is get either of the treatments for that very addiction! However, the DEA did recently announce new restrictions on hydrocodone (similar to oxycodone) but this minor effort may be too little, too lateiii.
So, which is better?
As I stated above, the Cochrane study found both methadone and buprenorphine are effective at keeping patients in treatment and off of heroin.
However, the study concluded that based on certain dosing patterns, methadone is more effective than buprenorphine. I would like to discuss this difference in a little more detail.
Methadone is More Effective than Buprenorphine
Several different types of studies were included in the Cochrane review and each of these studies used different dosing patterns for methadone and buprenorphine (low vs high, one dose vs flexible-dose). In cases of flexible dosing where the dose was selected to cater to the patient’s specific needs (similar to how most patients are treated), methadone was actually more effective at retaining patients in treatment than buprenorphine.
Low-dose methadone was also more effective compared to low-dose buprenorphine. This may be due to buprenorphine’s partial agonist activity and at a low dose it may be insufficient to satisfy the withdrawal symptoms and cravings, especially if the addict is used to very high doses of heroin. Importantly, methadone and buprenorphine given at medium and high doses were equally effective at keeping patients in treatment and off of heroin.
Implications for Drug Addiction Treatment
What do all of these findings mean for treatment? They mean that for some patients buprenorphine may not work while for all patients methadone will likely be effective. This is important to remember because access to methadone is still much more limited than access to buprenorphine.
It should also be noted that methadone requires daily dosing while buprenorphine, which acts longer than methadone, may only need to be taken every 2-3 days (though some patients still require daily dosing). For some patients, a prescription for buprenorphine to take every other day may be a much better option than methadone. However, due to its dose ceiling, buprenorphine may not be able to satisfy the craving and block the withdrawals if the addict is used to very high doses of heroin and the patient may have no other option than methadone.
Methadone vs. Buprenorphine: A summary
In conclusion, so which one works better?
Due to its partial agonist effects, some have argued that patients should be started on buprenorphine and then switched to methadone . But in the end, both are relatively safe and effective medications at preventing withdrawals, blocking craving, and keeping an addict off or heroin so they can live a life not centered on drug use. The best medication for treatment should be selected based on the patient’s history and severity of addiction and tailored to the patient’s needs. The most effective medication, methadone or buprenorphine, is the one that helps the patient.