Medications

Many people find, at least the first few drinks, cause a euphoric (pleasurable) feeling. This is because one of the ways that alcohol functions in the brain is to release endorphins in your reward centre. Endorphins are your own opioids. Naltrexone is an opioid blocker so the euphoric effects of alcohol are not experienced if naltrexone has been ingested. It does not decrease intoxication. Both the physical craving and the psychological reinforcement associated with alcohol consumption are reduced by this.

As time goes by, it allows the patient to better refrain from or decrease the quantity of alcohol consumed. Furthermore, since naltrexone does not cause dependence or have other properties for dependency, it is safe for medical supervision over long periods.

Naltrexone can reduce cravings, lower incidence of relapse and reduce frequency of heavy drinking.

Gabapentin is a prescription medication initially approved for the prevention of seizures but now used mostly for chronic, especially nerve pain. It is also used as a mood stabilizer and is effective in managing alcohol withdrawal. It also decreases alcohol craving.

There is a system in the brain to inhibit signals called the GABA system. Alcohol activates this system. Gabapentin also works at these receptors. When you quit or slow your drinking the gabapentin can activate the GABA receptors essentially replacing the alcohol with the advantage that gabapentin is not intoxicating.

Most people that have decreased their alcohol consumption feel day-time anxiety. They then start to think they just need a drink to “steady their nerves”. By stimulating the GABA system these symptoms resolve. Similarly, sleep disruption is also very common. Again GABA activation improves sleep so the urge for a “night cap” resolves.

The Sinclair Method (TSM) for Alcohol Use Disorders is an evidence-based treatment for problematic drinking developed by Dr. John D. Sinclair. Unlike traditional treatments with Naltrexone where the medication is taken each day, with TSM you only take naltrexone on drinking days and taken 1 hour before the first drink. (TSM) is a treatment that uses a technique called pharmacological extinction—the use of an opiate blocker to turn habit-forming behaviors into habit-erasing behaviors. The effect returns a person’s craving for alcohol to its pre-addiction state. Over time, your brain learns not to associate alcohol with pleasure, resulting in reduced cravings and improved control over alcohol use.

When you take Naltrexone prior to drinking, it blocks endorphins, the naturally occurring opiates in the brain, from being released when alcohol is consumed.

When the endorphins are blocked, there is no “buzz” or rewarding experience, and the alcohol doesn’t make you feel the pleasure that drives you to drink excessively. Sinclair believed this euphoria is what drives people to drink and that by blocking it the brain would extinguish the association between alcohol and the euphoria.

An important component of TSM is moderating your drinking – it is not enough to just take the medication.

Moderating means drinking 1 standard drink per hour. If you finish it in 5min then you can drink something non alcoholic. After an hour you ask yourself if you want another drink. If so then have one standard drink in the next hour. When drinking only at this pace most drinkers dont get intoxicated and dont lose control. If TSM works for them they usually only have a few and lose interest.

TSM is worth a try for someone still drinking but we also discuss it even with those who have quit and if they are interested we provide them with naltrexone to try in the situation where they relapse.

Sinclair’s original human study found about 75% of people in the group counselled to moderate their consumption of alcohol and taking naltrexone before drinking were able to consume alcohol at safe drinking levels (for men no more than 15 standard drinks per week, no more than 3 at a sitting) or be abstinent. The study was repeated by another researcher a few years later and found 45% of the people in the “Sinclair” group hit the combined endpoint of abstinence or safe drinking levels. Given that attempts of abstinence may only be successful 15% of the time many people are willing to try TSM.

Extinction usually occurs within 3-4 months and may happen quite rapidly.

About one quarter of those on TSM become 100% abstinent. Those who continue to drink will have to take their medication prior to drinking for as long as they continue to drink.

People that are using or prescribed opioids can not start TSM.

Below is an informative link to a Ted Talk video that describes the Sinclair Method and use of Naltrexone in more detail.
https://www.youtube.com/watch?v=6EghiY_s2ts

Acamprosate – Acamprosate is a medication which reduces cravings in alcoholism. It is thought to stabilize chemical signaling in the brain that would otherwise be disrupted by alcohol withdrawal. While it can be effective, it is typically only used in people that have not drank in the last 4 days.

Topiramate – Topiramate, sold under the brand name Topamax among others, is an oral medication usually used to treat epilepsy and prevent migraines. For epilepsy, this includes treatment for generalized or focal seizures. It is also used off-label for alcohol dependence and essential tremor which may improve sleep and mood disturbance in early abstinence.

Baclofen – Baclofen tablets are a muscle relaxant that treats muscle spasms. It relaxes your muscles, which reduces muscle stiffness. This may increase periods of abstinence.

Varenicline – Varenicline, sold under the brand names Chantix and Champix among others, is a medication used for smoking cessation. May be useful, especially for tobacco users with AUD.

Methadone is a synthetic opioid used medically to treat opioid use disorder (OUD). Advantages include a long half life (number of hours it takes to metabolize one half the dose). This enables it to be used once daily after the dose is titrated (adjusted). Another advantage is that it is a full agonist (it fully stimulates the opioid receptors). This allows us to start it even if patients are not in withdrawal.

Disadvantages include a potentially long titration time because methadone is potentially dangerous, especially during the titration phase. For this reason we need to start at a low dose because the dose accumulates (blood level increases, even though the dose remains the same) for the first 4 days in the average person so we only increase the dose after days 4-7. Given the very high tolerance of some patients that use fentanyl analogues it may therefore be several weeks before they are withdrawal free for 24 hours. At lower doses the methadone may only prevent withdrawal for a few hours.

Suboxone is a synthetic opioid used to treat opioid use disorder (OUD). It contains a combination of two medications, buprenorphine and naloxone. Buprenorphine is the active ingredient, the naloxone only becomes important if the person dissolves the tablets and injects the solution.

Buprenorphine has 3 significant attributes. First it is a partial agonist. The fact that it only partially stimulates opioid receptors makes it much safer but can also make it more difficult to use.

Second, it has a very high affinity for opioid receptors and will kick other opioids off opioid receptors they are occupying. This has a safety advantage – it is less likely for people to overdose if they use illicit opioids when they are already on buprenorphine. This of course is dose dependent – higher doses are more protective. It also means that people have to be in moderate to significant withdrawal when they first take it or it may make their withdrawal worse.

Third, If it is swallowed it has minimal effect. This makes it safer – less toxicity if a child or opioid naive person swallowed it. Therefore it is taken sublingually (under the tongue) or trans buccally (the film will stick to the inside of the cheek and dissolve). The medication dissolves then absorbs into the mucosa and then into the blood. In these methods the medication enters the systemic circulation and bypasses the liver. Medications that are swallowed are absorbed into the portal circulation which passes through the liver. The liver denatures buprenorphine.

Overall, especially if a person is in enough withdrawal buprenorphine is a very good choice because of its safety we can get people titrated to 24 hours of relief from withdrawal in 1-2 days in most cases. Overall it has less side effects than full agonist opioids.

Sublocade is a special form of buprenorphine. Unlike the tablets or film that have to be taken daily, Sublocade is a depot(dee-poh) medication – it is injected under the skin (subcutaneous) by trained staff members. It is formulated to last for 4 weeks but some patients find it lasts 5 or 6 weeks. Typically there is no titration, everyone eligible (you must have been on at least 8mg of buprenorphine in the past) gets the same amount for doses 1 and 2 (300mg) and for dose 3 there are 2 choices 300mg or 100mg). Sublocade is injected as a liquid (either 1.5ml or 0.5 ml depending on the dose – note that a teaspoon is 5ml). After injection a semisolid collection forms – it is this that releases the medication at a constant rate for the 4+ weeks. After this it continues to release buprenorphine at ever decreasing amounts for a few months.

Sublocade has the advantage of making it very easy to have a dose of medication every day for that month. At our clinic, only one visit a month is required to stay on the treatment.

Kadian is also known as SROM – sustained release oral morphine.

At our clinic it is typically used for 2 different purposes. First, to speed the titration of people starting methadone. As mentioned above one of the problems with methadone is it accumulates, potentially making stabilization (getting to a dose that lasts 24 hours) dangerous. As kadian lasts 24 hours but doesn’t accumulate, we can add it to the methadone dose. This raises the total dose of opioids being provided. Methadone is increased every 4th day, the Kadian stays the same. Once the person is stabilized we increase the methadone by 10mg and decrease the kadian by 100mg – in most cases the patient remains stable, if not we readjust.

In this manner we can cut the time to get to 100mg of methadone from 16 days (the minimum time) to methadone 70mg and kadian 300mg (the equivalent of methadone 100mg) to 8 days. We are interested in the time saving because our goal is to get people to stop using fentanyl analogues as quickly as possible – this usually doesn’t stop until after they are stable.

At this clinic we do not keep people on kadian and methadone together indefinitely.

The second manner that we use Kadian is called a Kadian Bridge. We use Kadian to bridge people from methadone to buprenorphine if the person’s desire is to switch medications. There are a number of reasons this may be requested.

Methadone takes a long time to wash out once a person stops it. If someone is only at 30-40mg we typically manage this by having the patient kip one day of methadone. We provide them with instructions on how to do a home induction (start buprenorphine) and provide them with buprenorphine to take at home when they are ready.

For people at higher doses of methadone we stop the methadone and start the Kadian. If the dose is good we have them use Kadian for approximately 10 days while the methadone washes out, then they stop the Kadian and take buprenorphine with them for a home induction when they are ready. We then see them in the office, adjust the dose or put them on Subocde if that is their desire.

Note that all the OAT medications above are covered by Ontario drug benefits, NIHB and many private insurers.