Prescribing medications for opioid use disorder is one of the most rewarding aspects of my career, and it's not that hard to do. Honestly, it's probably easier than treating diabetes or heart disease or depression. It's incredible to see the diagnostic features of the disease melt away when patients are doing well on treatment. When people are engaged in evidence-based treatment for opioid use disorder, their physiologic dependence is treated, no more withdrawal no more craving. But over time they also get their job back, they reconnect with their family. They start to regain the things that were lost as a result of their addiction, patients will often say to me, I finally feel normal, I've never felt normal before and now I finally do. Watching patients walk into your office feeling at their worst and leaving feeling better than they have in months, is so gratifying. In this lesson you will learn about three evidence-based medications that are highly effective for the treatment of opioid use disorder. What do I mean when I say highly effective? Let's start with an activity to have you guess what medications can and cannot do. I will list a series of statements, and you will note whether you think it's true or not. Medications can decrease opioid withdrawal symptoms, medications can block the effects of other opioids. Medications can reduce or eliminate cravings for opioids, medications can decrease harms related to opioid use, including exposure to infectious diseases and overdose. Medications can stabilize the complex neurobiological changes resulting from long-term use. Medications can ultimately reduce morbidity and mortality. Surprise, medications have the potential to deliver all of these benefits. By watching this lesson you'll learn how each medication works, where they are available along with basic information on dosage and side effects. In order to guide your patients to choose the medication that best suits them. Okay, let's take a moment to review methadone, buprenorphine and naltrexone, all of which have a different action at the mu opioid receptor. Receptors which are found on human cells are a lot like locks, and ligands or our bodies chemicals that bind them are the master keys. Substances that mimic these master keys and bind to the receptor like a key in a lock either caused or blocking effect. Methadone is a full agonist, which means it binds the mu opioid receptor and causes an effect, it acts like a key in the lock. Because of this methadone lessons the painful symptoms of opioid withdrawal and blocks the euphoric effects of opioid drugs. Buprenorphine is a high affinity partial agonist at the mu opioid receptor and an antagonist at the kappa opioid receptor. At the mu opioid receptor buprenorphine acts like a key that isn't fully able to open the lock. As a result, buprenorphine does not fully stimulate the opioid receptor, and because of its high Affinity it blocks the effects of other opioids. It has a ceiling effect meaning that its effects will plateau and will not increase even with repeated dosing. Also because of its partial agonism it's less likely to lead to dangerous respiratory depression. Naltrexone is an antagonist at the mu opioid receptor meaning that it blocks rather than activates them you opioid receptor, effectively blocking the effects of opioids if they are used. Naltrexone will fit in the lock like a key, but it's not able to open the lock. Additionally because of its high binding affinity, it will not allow other keys into the lock to open it. So, to recap how each medication works, methadone generates the opioid effect, and could potentially cause respiratory depression at very high doses. Buprenorphine generates a limited or ceiling effect and naltrexone blocks the effect, in the presence of opioids naltrexone would displace the opioids from the receptor and cause opioid withdrawal. Using a lock and key is one analogy you can use to remember and describe the mechanism of action. I know some of my colleagues use different examples. For instance, I've heard a light dimmer metaphor used, in which methadone turns the light all the way on buprenorphine turns it halfway on and Naltrexone turns the light off. Now let's review the treatment considerations for each medication, methadone for the treatment of opioid use disorder is taken orally. Typically in liquid form and has an onset of action between 30 and 60 minutes. The duration of action is between 24 and 36 hours to treat opioid use disorder. When used to treat pain duration of action is much shorter between six and eight hours. For the treatment of opioid use disorder, methadone should be tried traded to alleviate withdrawal symptoms in the short term, and decrease craving in the long-term, all while minimizing adverse effects. Methadone is the oldest treatment for opioid use disorder and has been very well studied. When used as part of a comprehensive treatment program, compared with placebo or no treatment methadone has been shown to increase treatment or tension. Decrease illicit opioid use decrease hepatitis C and HIV seroconversion, decrease criminal activity, increase employment, improve birth outcomes, and increase survival. It's important to note that methadone can only be administered in a state or federally certified opioid treatment program for the treatment of opioid withdrawal in an outpatient setting. Once initiated patients must go to the treatment program on a daily basis to receive their dose dispensed by a nurse. Additionally patients are required to engage in counseling as directed by the treatment program. Over time patients can earn take-home bottles after establishing clinical stability. Potential adverse effects are often dose-related and include things like constipation, sweating, sedation, a potential for hypogonadism, and a potential for prolonging the QT interval on the EKG. Sedation may be particularly pronounced in patients who take other central nervous system depressant medications, like benzodiazepines either by prescription or illicitly. However, as endorsed by the FDA, methadone treatment should not be withheld from patients taking benzodiazepines. Rather, the provider should assess for a sedative use disorder and provide treatment as appropriate. If the patient does not meet criteria for a sedative use disorder, then the provider should work with the patient to mitigate any risk. One of the questions that I often get asked almost immediately when patients present for methadone treatment is, how long do I need to be on this medication? The answer is plain and simple, and would be the same answer I would give to any patient who wanted to know how long they needed to be on insulin for diabetes, and the answer is long enough. You need to be on the medication long enough to achieve clinical stability and to address the treatment goals that we discussed at the outset of treatment. Another thing I've often seen is family members demanding that we discontinue methadone treatment on their loved ones, because they don't believe in it. My response is, methadone is an evidenced-based life-saving treatment, it's not a religion. The next medication is buprenorphine, which can be taken sublingually on a daily basis or subcutaneously on a weekly or monthly basis. The dosage range for sublingual buprenorphine is between 2 and 24 milligrams with the target dose of 16 milligrams. The onset of action for sublingual buprenorphine is 1 to 4 hours with a duration of action between 36 and 48 hours. Induction may be challenging because of the partial opioid nature of buprenorphine, and its high receptor affinity. A patient must be experiencing mild to moderate opioid withdrawal in order to safely be initiated on buprenorphine. The presence and degree of opioid withdrawal can be assessed using the clinical opioid withdrawal scale or COWS. You can find more information on this either in the download section, or in the next reading. Unlike methadone, buprenorphine can be prescribed in settings other than an opioid treatment program. Such as in an office based setting or through innovative care delivery settings like in the emergency department. That being said, in order to prescribe buprenorphine in the outpatient setting for opioid use disorder, the provider must undergo special training to be issued a waiver from the drug enforcement agency. The training is 8 hours long for medical doctors and 24 hours long for physicians assistants and advanced practice registered nurses. The training can be in person online or a combination of both. Additionally, there are limits on how many patients a provider can treat at one time. The optimal duration of treatment is unknown, and the decision to discontinue treatment with buprenorphine should be carefully decided on between the patient and the provider. Once the decision is made, the process of safely tapering the buprenorphine dose often span several months. When discussing treatment options, it's not uncommon for patients to say to me. I tried buprenorphine before and it didn't work, once I was weaned off buprenorphine I started using again. Let's think for a moment about treating diabetes, as clinicians we judge how well a treatment works for our patients by seeing how they do while they are taking the treatment. On insulin my patients sugars went from 300 to 130, therefore the insulin works. However, for some reason with opioid antagonist treatment, including methadone and buprenorphine. It's not uncommon for both patients and providers to think that the marker of a success of the treatment is how will they do when they are weaned off the medication or discharged from a treatment program. This doesn't make any sense and is not the way we judge treatment success for any other chronic disease. Typical adverse effects of buprenorphine during induction or headaches and effects on sleep. Dose-related adverse effects include constipation, buprenorphine does not appear to have the same degree of concerns for QT interval prolongation on the EKG as methadone does. Providers are sometimes concerned about how to treat pain while patients are maintained on buprenorphine. Studies have shown this can be effectively done by using non-opioid medications or other modalities or adjusting the buprenorphine dose or dosing schedule. It's important to note that because methadone and buprenorphine act as agonist at the mu opioid receptor. These medications cannot be stopped abruptly or opioid withdrawal will occur. Due to the long-acting nature of both of these medications, withdrawal may not set in for one to two days if stopped abruptly. Now naltrexone acts differently than methadone and buprenorphine because it's an antagonist at the mu opioid receptor. So it does not lead to physical dependence and does not produce the reinforcing or rewarding effects of opioid antagonists. Exogenously administered opioids are unable to overcome Naltrexone is blocking effect, and therefore do not produce any reinforcements. Naltrexone is available in a once-daily oral formulation and a once monthly injectable depot formulation. The oral form was found to be no better than placebo with regard to treatment retention or decreasing opioid use. The extended-release Naltrexone is the only formulation approved by the FDA for the treatment of opioid use disorder. The primary adverse effects were fatigue and administration site-related conditions. Recent randomized studies have shown that if patients are able to be inducted on to extended release naltrexone. The medication is non inferior to buprenorphine in terms of both safety and efficacy. One of the barriers to treatment with naltrexone is posed by its mechanism of action and long half-life. A patient must exhibit a prolonged period of opioid abstinence to be able to safely take naltrexone without precipitating opioid withdrawal. For many patients this is not possible as the most common reason cited to ongoing opioid use among patients with opioid use disorder, is to stave off withdrawal symptoms. So while naltrexone cannot be used for withdrawal management, it is an attractive option because it significantly reduces overdose risk, it acts as a tool to decrease risk associated with relapse. Well, not a treatment for opioid use disorder, I want to stress the importance of naloxone also known as narcan. All patients with this chronic disease and their close contacts should have ready access to naloxone, with a firm understanding of how to administer it in the case of an overdose. In every state patients can obtain naloxone from a pharmacy without having to see a provider. Even all patients prescribed opioids for the treatment of chronic pain should also have naloxone given the risk of respiratory depression. Some people think that by recommending naloxone to patients with opioid use disorder is enabling drug use. Do we consider prescribing an epi pen to patients with an allergy to bee stings is enabling? No, of course not, we realized that bee stings are dangerous to people with allergies, and we give them and their loved ones education on how to recognize an allergic reaction and how to save their life should it occur. A patient with opioid use disorder is no less important to their family than a patient with allergy to bee stings. Properly recommending medications for opioid use requires an accumulation of skills. The same skills you have hopefully been learning and practicing in this course, and use in the recognition and treatment of other chronic medical and psychiatric diseases. First, should screen to identify at-risk patients, and assess them in order to diagnose an opioid use disorder. Then you should evaluate using the ripped are framework to organize the information regarding the patient's treatment plan. It's helpful to have a working knowledge of the treatment providers in your area including opioid treatment programs and office-based buprenorphine programs. Better yet, you should consider getting a buprenorphine waiver yourself. Lastly, no patient with presumed or diagnosed opioid use disorder should leave a clinical encounter without a prescription for or instructions on how to use naloxone. In summary, there are three FDA approved options for the treatment of opioid use disorder, all with different mechanisms of action and treatment implications. Choosing one over the other should be a collaboration with the patient taking into account the following. The risk for withdrawal, the treatment setting availability and preferences for instance an office-based setting or in opioid treatment program. And dosage concerns taking something daily or getting a monthly injection. Medications are evidence-based and life-saving treatments that should be made available to everyone that needs it. Every door into a healthcare system should present an opportunity for patients with opioid use disorder to be linked to effective treatment.
