The Problem with Vivitrol®

(https://www.vivitrol.com/opioid-dependence/what-is-vivitrol)

Fascinating post by guest contributor Amy Dunn, graduate student at the Rockefeller University!


What is Vivitrol®? This question is posed in countless ads depicting attractive young people across target states, such as MA, NY, NJ and PA. The ads do little to answer the question – instead just giving a drug name and a website. Vivitrol®, made by the Boston-based company Alkermes, is the brand name for the drug naltrexone and is used to treat both alcohol and opiate addiction.

Opiates like heroin or oxycodone work by stimulating the mu opioid receptor in the brain. This leads to the euphoric and rewarding effects that are characteristic of these drugs. The two most popular medications for treating opiate addictions, methadone and buprenorphine, both work by stimulating that same receptor in a slightly different way. This relieves the cravings, but doesn’t cause the same “high” as heroin or oxycodone. Methadone and buprenorphine are known as agonist, or replacement, medications. Dr. Simon Says Science wrote an excellent article for Addiction Blog that compares methadone and buprenorphine and explains how they work in greater detail. Naltrexone, on the other hand, is an antagonist of that same receptor – meaning that it completely blocks the effects of any opioid. While it seems counterintuitive, medications that stimulate the mu opioid receptor and medications that block the mu opioid receptor have both been proven to be effective treatments for opiate addiction.

Naltrexone was approved by the FDA in the 1980’s and was originally formulated as a daily pill, however it was difficult to get people to adhere to taking their medication. Because naltrexone is a mu opioid receptor antagonist, it can lead to unpleasant feelings that are the opposite of the euphoria felt with an opiate agonist. People with addictions could stop taking the medication if they wanted to get high instead. Because of these adherence issues, the drug bounced around between companies. In addition to these issues with compliance, it was difficult for companies to market an addiction medication because of the social stigma. Addiction is often seen as a moral problem instead of a medical one, which makes selling medications for addictions very difficult.

Naltrexone became far more practical when it was reformulated as an extended-release injection. The extended-release injection lasts for a month, greatly reducing the problem of adherence. Vivitrol®, the brand name for the extended-release naltrexone introduced by Alkermes, was first approved in 2006 for the treatment of alcohol addiction. Following a successful clinical trial in Russia, it was also approved for treatment of opiate addiction in 2010. Despite poor initial sales, the popularity of Vivitrol® has grown rapidly in the past couple years.

Vivitrol® Sales: (https://www.scribd.com/document/351102245/Alkermes-2016-Analyst-and-Investor-Event-Presentation#from_embed)

 

Vivitrol® is still far less utilized than methadone and buprenorphine, but this is expected probably because it is much newer on the market. Importantly, not everyone responds well to methadone or buprenorphine, and having another option for the treatment of opiate addiction should be a good thing for everyone. However, a disturbing pattern has emerged in the past couple years regarding the ethics of Alkermes’ marketing strategies and scientific data. They are missing key scientific data, and actively engaging in strategies to undermine the use of agonist medications that compete with Vivitrol®. While these marketing strategies may or may not be illegal, they still raise important questions about the ethical obligations of pharmaceutical companies to their patients.

The Science on Vivitrol®

In order for the FDA to approve a drug, a drug company must first prove that the drug is effective through a clinical trial. Clinical trials are very tightly regulated in the US which makes sense because you’re testing a drug that is technically still experimental and could be dangerous to people. Not only do you need to prove that your drug is safe, but you also need to prove that it is at least as effective as other drugs out there that treat the same condition. This is where there are holes in the data on Vivitrol®.

The clinical trial that convinced the FDA to approve Vivitrol® was done in Russia.3 Clinical trials are done in other countries for many reasons. Companies may be trying to skirt the tight regulations here in the US, or they might just need to work with a patient population that is found more commonly in other places. The FDA reviews the study design and the data to see if they want to approve the drug regardless of where the study was done. The clinical trial on Vivitrol® was designed to see if Vivitrol® was effective for treating opiate addiction, but did not compare it to either of the other approved medications for opiate addiction (methadone or buprenorphine). Neither of these agonist treatments is available in Russia. In fact, both are illegal because they are opiate agonists. Alkermes only needed to prove that Vivitrol® was more effective than placebo in this case. The results were promising – almost 90% of the addicted persons who received the naltrexone shot remained abstinent during the test period, compared to just over 60% of the control group. This was enough evidence to get FDA approval, however to date there are no clinical trials comparing Vivitrol® to either methadone or buprenorphine. In addition, there was no follow-up study examining the long-term outcomes of the participants of the clinical trial in Russia.

Since it has been approved, there have been several other clinical trials examining the efficacy of Vivitrol® in different populations (although none of these studies compared it to buprenorphine or methadone). There are still concerns about adherence to Vivitro®, as well as the possibility that a person could take a dangerous amount of opioids in order to overcome the blockade effect. Because it’s an antagonist, if an addicted person takes naltrexone while they still have opiates in their system, the naltrexone will both stop the euphoric effects of the opiate and also cause withdrawal symptoms. In fact, a person has to be over a week opiate-free and have already gone through withdrawal before they can begin naltrexone treatment.

However, no medication is ever perfect. While there are still unanswered questions about Vivitrol®, it is clearly an addition to the toolbox that healthcare providers can use to help people fight addictions. It is important that these scientific concerns are discussed and addressed, and that these issues are clearly presented to the public so that people can make informed decisions about their medications.

The Marketing on Vivitrol®

(www.vivitrol.com)

To understand more about how Alkermes is advertising Vivitrol®, we can look at a screenshot of their main website listed on their advertisements (www.Vivitrol.com). This language – “the first and only once-monthly, non-addictive medication” is problematic.  While they are correct in characterizing naltrexone as “non-addictive”, this wording implies that the other medications that are available (methadone and buprenorphine) somehow are addictive. This same language is often used in a 2016 investor presentation as well, where they describe agonist therapy as “maintain[ing] physiologic dependence on opioids”. This is scientifically correct; a person who is using agonist medication may indeed be dependent on their medication. This simply means that they would experience negative physiological consequences if they abruptly stopped use. It does not mean that they are addicted. “Addiction” is a physiologic dependence combined with compulsive drug-taking despite negative consequences. Alkermes is conflating these two terms in a way that is confusing, and is meant to manipulate the consumer into equating agonist therapies with addicting opiates of abuse. While their statement that agonist therapies lead to dependence is not incorrect, it is still reinforcing a very damaging stereotype that agonist therapy is just “replacing one drug with another.” This stigma against agonist therapies is a major hurdle for the treatment of opiate addictions. Alkermes actively reinforces and uses this stereotype in order to promote Vivitrol® as the “only non-opioid treatment.”

(https://www.scribd.com/document/351102245/Alkermes-2016-Analyst-and-Investor-Event-Presentation#from_embed)

In addition to portraying Vivitrol® as a better and safer alternative to agonist therapies in the public sphere, Alkermes is also deliberately promoting this view in the political realm. This is noted in the slide from an investor presentation that outlines their marketing strategies, above.  NPR and Side Effects Media published an excellent article detailing their investigation into Alkermes’ political involvement.  They describe Alkermes lobbyists presenting to government committees on addiction therapy and promoting the idea that agonist therapies are “replacing one drug with another”. There is overwhelming scientific evidence supporting methadone and buprenorphine as effective treatments for keeping people with addictions off of heroin and able to live their lives without experience frequent drug cravings. Despite this, there are many decision-makers in the government who do not want to support their use in treatment. Republican Rep. Tim Murphy described agonist therapy as “government –supported addiction” at a meeting in March 2015. He has received political donations from Alkermes. Tom Price, the new Health and Human Services Secretary, received a great deal of criticism for his statement that agonist therapy was “substituting one opioid for another” – despite the department’s website explicitly stating that it supports these kinds of evidence-based treatments.

Alkermes’ strategy of reinforcing of this stereotype leads to real policy consequences. The NPR and Side Effects Public Media report describes several bills that contain language steeped in these stereotypes – specifically instructing treatment providers to strive for “the goal of opioid abstinence.” This is beneficial for Alkermes, as Vivitrol® is the only non-opioid treatment available. The science however, does not indicate that opioid abstinence leads to better outcomes for patients than maintaining their agonist therapies. The report includes drafts of several bills that even mentioned Vivitrol® by name, although it was later removed because of ethical concerns. Alkermes lobbyists have also supported tightening regulations for methadone and buprenorphine, which is incredibly problematic given how restrictive the regulations already are for treatment providers.

Alkermes may not be making explicitly false claims in its marketing, but it is certainly playing off of existing harmful biases in order to further their sales. Whether or not this is illegal is debatable; it is illegal under the Federal Trade Commission for companies to “mislead” consumers. At the very least, it is incredibly unethical for a company to be so actively promoting stereotypes and policies that harm the very patients that they claim to be helping. This falls under the larger umbrella of the issues of advertising, pricing and political involvement of the pharmaceutical industry in our country. While there are no easy fixes, it is important that companies like Alkermes are held responsible for their unethical behavior and that consumers are able to make informed decisions about their treatment based on the available research.


About the Author: Hello! I’m currently finishing my 3rd year of graduate school at Rockefeller University. I’m studying the cell signaling changes caused by drugs of abuse and investigating the ways we can use those different pathways to treat addictions. In addition to learning more about the science of addiction through my research, I’m also interested in learning about the different political and social issues surrounding drug addiction. All of the views and opinions here are entirely my own and definitely don’t reflect those of my lab or institution! My email address is adunn@rockefeller.edu.

Response to the June 2017 New Yorker Article on the Opioid Epidemic

At this point, I would think that knowledge about the vastness and seriousness of the prescription opioid and heroin epidemic, the biggest threat to American health and well being since the HIV/AIDS epidemic, would be common knowledge. Of course, given the abundance of shiny Internet things to tantalize easily distracted Americans, this is unfortunately not necessarily the case. Thankfully the New Yorker, with their characteristic excellence in reporting, has just released a superb and humanizing article on the opioid epidemic in their June 5 & 12, 2017 issue.

Read the article here.

The piece puts a much-needed human face to the horrors and misery of opioid addiction and the too-frequent death by overdose. Margaret Talbot, the article’s author, zeroes in on Berkeley County, West Virginia, in the heart of a region of the country hardest hit by the epidemic. I don’t want to give away much (because you should actually just read the article) except that the stories are heart wrenching yet balanced, and thorough in way that only the New Yorker can deliver. While the article is largely about the lives of people affected by and fighting against the epidemic, I was disappointed with a couple of points that were either made incorrectly, weakly, or not at all.

First, the article barely talks about how the epidemic arose in the first place. It mentions Purdue pharmaceuticals, the bastards behind Oxycontin (drug name: oxycodone), and that prescription opioid abuse led to heroin addiction but does not describe how the surge in addiction to prescription opioids occurred in the first place. The article describes the main problem with Oxycontin is that it can be crushed and snorted but a 2010 formulation of the drug reduced this risk. While this is indeed true, the article neglects to mention that when someone is first prescribed an opioid like Oxycontin for chronic pain (as was the case in the late 90s and early 2000s despite any evidence for the effectiveness of opioids in the treatment of chronic pain), the addictive potential of opioids often led to opioid substance abuse disorder in people who took it as prescribed (see this comprehensive article for more info). This is the big point, many of the people that eventually abused opioids started down that road by taking the drug as prescribed! Talbot incorrectly frames the big picture problem but she then goes on to correctly describe how those addicted to prescription opioids found their way to the cheaper and more abundant heroin.

The article goes on to mention the CDC’s release of guidelines on opioid prescription but fails to cite that this guidance came out as late as March, 2016, well after the epidemic had already taken root and thousands were already addicted and dying of overdose (I wrote an article on the CDC’s guidelines last year and highly recommend you read that article too if you want to learn more). The CDC’s guidance is mainly about the point I made above, that the over-prescription of opioids is the real cause of the epidemic, not just the crushable version of Oxycontin, and the limitation of opioid prescription is one of the huge policy interventions that is needed.

Later in the article, Talbot introduces us to Dr. John Aldis, a retired U.S. Navy Physician and resident of Berkeley County, WV who took it upon himself to educate people on how to use Narcan (generic drug name: naloxone), the treatment for opioid overdose. Dr. Aldis makes the critical point about the importance of medication-assisted treatments such as Suboxone (generic drug name: buprenorphine) and methadone. I appreciated the point made in the article that some patients may need these vital treatments long-term, or even for life, to combat the all-consuming single-mindedness of opioid addiction. However, beyond this passing mention, I felt that medication-assisted treatment was only weakly covered. There is still a great deal of ignorance about these treatments. Indeed, current HHS secretary Tom Price falsely characterized them as “replacing one opioid with another” and was majorly criticized by addiction experts. The reality is that there is overwhelming scientific evidence (I’ve written plenty on this site) describing the effectiveness of methadone and buprenorphine at 1) keeping addicts off of heroin, 2) allowing them to be able to live their lives without suffering from withdrawals and cravings, and 3) most importantly, keeping them alive. Talbot could have done a much better job of really hammering these points home but she seemed reticent, for some reason, to discuss it in detail in this article.

Finally, the article repeatedly emphasizes the importance of rehab clinics and tells the story of a huge victory for Martinsburg, WV (a town in Berkeley County) when the city council agrees to open a clinic in the town itself. I do not want to discount the importance of an addict assessing their addiction and taking an active role to end it, but this article does miss another critical point: rehab clinics only exist because addiction medicine is not part of medical school curricula and most hospitals are ill-equipped to treat those suffering from addiction. I feel this article could have really made the case for the importance of training for doctors in addiction medicine and the necessary shift that needs to happen for addiction treatment, a move away from overpriced (and often ineffective) private rehab facilities, and to public hospitals. Unfortunately, this point was not made.

Despite these missed opportunities, I commend Talbot and the New Yorker for a well-written article and thank them for this important piece that I encourage all to read.

 

The Laws You Never Heard Of that Will Help to Fight the Opioid Epidemic

When a politician is in his or her final few month in office (because either they lost their re-election or simply decided not to or can’t run), they call this the “lame duck” period. President Obama’s last few months in office were anything but “lame”.

On December 14, 2016, in a rare move of bipartisanship, Obama signed into law the massive 21st Century Cures Act. This law provides a boost in funding for NIH (which includes $1.8 billion for the cancer moonshot initiative), changes to the drug approval process through the FDA, and ambitious mental health reform. This huge bill has the stated purpose of “To accelerate the discovery, development, and delivery of 21st century cures, and for other purposes.”

I’m willing to bet many people were totally unaware of this legislation that could help millions. There are some parts that are controversial and, as with any large piece of legislation, some provision that benefit this interest or that have been worked in (the changes to drug approval at the FDA will likely benefit Big Pharma). I’m not a health policy expert so I’m not about to go through and discuss line-by-line the winners and losers in this law (if you want a more in depth discussion: NPR, Washington Post, and PBS have all written articles on the law).

There’s one piece of the law that I am particularly thrilled about: $1 billion over 2 years for treatment for opioid addiction. That’s rights billion, with a “B”. The money is to be distributed to states in the form of block grants (block grants are in essence a large allocation of federal money to be used for a specific purpose given to states but the details of how that money is used is decided by the states themselves).

This is an unprecedented amount of funding earmarked exclusively to fight the opioid epidemic that is still raging in the US. The funding is to be used for expanding and increasing accessibility to treatment, such as life saving medication-assisted treatments such as methadone and buprenorphine. The federal money will also be used to train healthcare professionals to better care for people dealing with addiction, and a comparatively smaller amount for conducting research on how best to fight the epidemic, and other provisions.

I’ve written about methadone and buprenorphine and their effectiveness ad nauseam on this site and I am personally and thrilled to see a massive federal effort to increase access to these vital tools in the fight against the opioid crisis

The Cures Act comes on the heels of another promising piece of legislation, the Comprehensive Addiction and Recovery Act (CARA), signed into law by President Obama on July 13, 2016. This law includes provisions to expand the availability of naloxone–the medication used to save people from the effects of opioid overdose–to first responders, improve prescription drug monitoring programs, make it easier for healthcare providers to administer, dispense, or prescribe medication-assisted treatments, and other provisions.

The combination of these two pieces of legislation is a promising and much needed initial federal response.

However, this huge boost in funds for treatment in the Cures Act is only for 2-years. President Trump’s budget for FY18 would add $500 million for opioid addiction but most analysts think this is just a sneaky way of making it seem as if he’s supporting addiction treatment when the money has already been written in as part of the Cures Act. Further, his cuts to the Department of Health and Human Services (which contains the NIH and other agencies that administer the Cures and CARA laws) would make it difficult to launch any type of  effective response to the crisis.

Regardless of how things shake out, Trump’s massive cuts for everything that’s not the Department of Defense will likely hurt the fight against the opioid epidemic too. The real question is by how much?

 

5 Facts on the Opioid Epidemic: National Drug and Alcohol Facts Week

Spilled prescription medication --- Image by © Mark Weiss/Corbis
Spilled prescription medication — Image by © Mark Weiss/Corbis

Well, I’m a little late to the punch on this one but National Drug and Alcohol Facts week has been going and ends tonight. This public awareness campaign is now in it’s seventh year and is all about shattering the myths about addiction.ndafw_logoI might as well throw my belated hat in the ring and share 5 facts about the opioid epidemic.

Fact #1: The opioid epidemic in the U.S. has hit all demographic groups, regardless of race, gender, age, location, or socioeconomic status.

Fact #2: Prescription opioid pain medications like oxycodone can be just as addictive as heroin, even if taken as prescribed.

Fact #3: There is no scientific evidence that prescription opioids are effective at managing chronic pain; they are extremely effect for short-term, acute pain.

Naloxone_(1)Fact #4: Naloxone is a drug that counters the effects of opioids and can immediately reverse an overdose; you cannot get addicted to naloxone.

Fact #5: Buprenorphine and methadone are opioids that can help a person to fight their heroin addiction by satisfying their craving for the drug.

To learn more, here’s a short “Best of” from Dr. Simon Says Science on the Opioid Epidemic. Check out the posts below for oodles of info on opioids.

  1. What is naloxone? Should it be available over the counter?
  2. The CDC Fights Back Against the Opioid Epidemic
  3. Is Methadone an Effective Treatment for Heroin Addiction? YES!
  4. Morphine and Oxycodone Affect the Brain Differently
  5. Important: CDC Releases Report on Heroin Epidemic
  6. Methadone Maintenance Therapy Works-End of Story
  7. Paper Review-Initiation into Injection Drug Use and Prescription Opioids
  8. New Review Paper-The Prescription Opioid and Heroin Epidemic

 

Methadone vs Buprenorphine: Which is Better for Treating Heroin Addiction?

Check out my new post for addictionblog!

Is Methadone an Effective Treatment for Heroin Addiction? YES!

methadose_0

NEW BLOG POST FOR ADDICTIONBLOG IS UP NOW! ALL ABOUT METHADONE.

CHECK IT OUT!

Response to HuffPost Marc Lewis Interview on Addiction

So the Huffington Post runs a sub-blog on Addiction and Recovery and sometimes they present excellent reporting (for example, the piece on opioid addiction by Jason Cherkis who actually interviewed my boss, Dr. Mary Jeanne Kreek, for the article). But more often than not, they present quite variable reporting on addiction.  A recent interview with psychologist Marc Lewis, PhD is one such example.

Based on my own neuroscience of addiction background, I unfortunately find a number of Dr. Lewis’s claims not supported by scientific evidence and I believe the spread of such false statements can have the exact opposite of his intended effect—hurting more addicts rather than helping them. I do not claim to be the consensus voice of the addiction field but present my own arguments based on my own research and work done in the field. I also admit have not read any of Dr. Lewis’s books and am merely responding to the statements made in his interview. I include references at the end of the post.

The original interview between Carolyn Gregoire, Senior Health and Science Writer for Huffington Post and psychologist Marc Lewis, PhD

The questions (Q) by Carolyn Gregoire in the original interview are in bold, Dr. Lewis’s response (L) is italicized, and my response (S) is the un-italicized larger-size text.

Q: What’s wrong with the disease model of addiction? 

L: I know what scientists are looking at when they say addiction is a disease. I don’t dispute the findings, but I dispute the interpretation of them. They see addiction as a chronic brain disease — that’s how they define it in very explicit terms. 

My training is in emotional and personality development. I see addiction as a developmental process. So the brain changes that people talk about and have shown reliably in research can be seen as changes that are due to learning, to recurrent and deep learning experiences. But it’s not an abnormal experience and there’s nothing static or chronic about it, because people continue to change when they recover and come out of addiction. So the chronic label doesn’t make much sense.

S: The brain is a physical organ that operates under defined molecular biological principles. Drugs are physical chemical substances that perturb the molecular function of the brain. It is true that addiction is a process that can take months or even years to develop but the end result is a physical neurobiological change in how the brain functions [1, 2]. And when neuroscientists say chronic brain disease—or what my lab says A disease of the brain with behavioral manifestations—what we mean is that repeated drug use has caused a change is brain function which in turn results in a change in behavior. That doesn’t mean that this change is irreversible but, like other diseases, the first step to treatment is recognizing the underlying biological cause. Defining addiction as a chronic brain disease is not a judgment or interpretation of the development of addiction (which definitely does involve a learning and memory component [3, 4]) but is a statement asserting that drug addiction and drug cravings, compulsive drug use, and relapse are ultimately based on physical changes in the brain. It is important that we recognize this because otherwise we would not be able to treat it with effective and safe medications, in combination with other behavioral and psychological therapies.

Q: What’s problematic about the way we treat addiction, based on the disease model? 

L: Well, lots. The rehab industry is a terrible mess — you either wait on a long list for state-sponsored rehabs that are poorly run or almost entirely 12-Step, or else you pay vast amounts of money for residential rehabs that usually last for 30-90 days and people often go about five to six times. It’s very difficult to maintain your sobriety when you go home and you’re back in your lonely little apartment. 

What I emphasize is that the disease label makes it worse. You have experts saying, “You have a chronic brain disease and you need to get it treated. Why don’t you come here and spend $100,000 and we’ll help you treat it?” There’s a very strong motivation from the family, if not the individual, to go through this process, and then the treatments offered in these places are very seldom evidence-based, and the success rates are low. 

S: I strongly agree with this assessment. The rehab industry and many 12-step programs are ineffective, expensive, and rarely based on scientific evidence. The primary reason is that for decades addiction was thought of a problem of “spiritual weakness” or “lack of will power”. In reality addiction is a medical disorder based on physical neurobiological processes that make it seem like an addict has no “will power”, when in reality that addict’s brain has been hijacked to crave the drug compulsively and practically uncontrollably. However, again, I disagree that calling addiction a disease is what funnels people into rehab clinics. I believe it is the stigmatization of addiction that precludes treatment by doctors (unlike for every other disease), which in turn fuels admission into the rehab industry. Sadly, effective medications exist (such as methadone and buprenorphine for opioid addicts) that can flick a switch off in an addicts brain, satisfying their craving and allow them to live a normal live [5, 6]. Or medications such as naltrexone may be effective at reducing drinking in alcohol addicts but is not widely used [7, 8]. It is only recently that public acknowledgement of the biological basis of addiction and appropriate shifts in public policy are beginning to take place. Importantly, addiction medicine is beginning to become incorporated into medical school education and the first accredited residency programs in addiction medicine have been announced.

Q: There are lots of ways to trigger a humanistic response besides calling something a disease. So you would say that telling people who are in recovery for addiction that they have a “chronic disease” is actually doing them a disservice? 

L: Well, the chronic part is really a yoke that people carry around their necks. [Proponents of the disease model] say that this is important because this is how to prevent the stigmatization of addicts, which has been a standard part of our culture since Victorian times. 

But I think that’s just bullshit. I don’t think it feels good when someone tells you that you have a chronic disease that makes you do bad things. There are ways to reduce stigmatization by recognizing the humanity involved in addiction, the fact that it happens to many people and the fact that people really do try to get better — and most of them do. There are lots of ways to trigger a humanistic response besides calling something a disease.  

S: I agree that stigma is a huge problem with the treatment of drug addiction and mental health. Admitting you are an addict or depressed or know someone who suffers from these disorders is accompanied with unnecessary shame and fear of admission of the problem. I disagree that acknowledgement of medical/neurobiological basis of these disorders (ie calling them diseases) increases stigma but in fact do humanize patients. It helps alleviates shaming–both public and self–and can help an addict to seek evidence-based, medical treatment. Acknowledging the chronic nature of the disorder is not intended to make people feel bad but is merely truthfully stating the nature of the problem in hopes that it can be properly treated; denial can be lead to false and ineffective treatments.

Q: It can be difficult to comprehend the idea that something as severe as a heroin addiction is a developmental process. Can you explain that? 

L: First of all, let’s include the whole bouquet of addictions. So there’s substances — drugs and alcohol — and there’s gambling, sex, porn and some eating disorders. The main brain changes that we see in addiction are common to all of them, so they’re not specific to taking a drug like heroin, which creates a physical dependence. We see similar brain changes in a region called the striatum, which is an area that’s very central to addiction, which is involved in attraction and motivational drive. You see that with gambling as much as you do with cocaine or heroin. So that’s the first step of the argument — it’s not drugs, per se. 

From there, it’s important to recognize that certain drugs, like opiates, create physical dependency. There’s a double whammy there. They’re hard to get off because they’re addictive, like sex or porn is, but they also make you uncomfortable when you stop taking them. People try to go off of them and get extremely uncomfortable and then they’re drawn back to it — now for physical as well as psychological reasons. 

S: It is true that all addictions involve the striatum and there are similarities between the different addictions but to say that ALL addictions affect the brain in the exact same way is an absurd simplification. Different drugs absolutely DO affect the brain differently and have differences in addiction potential and relapse potential. To say addiction to heroin is identical to addiction to alcohol is identical to gambling addiction and therefore has nothing to do with the specific drug or behavior is just plain wrong. A wealth of evidence is gathering that addictions to different drugs progress differently and effect different brain systems, despite certain changes common to all [9]. For example, even opioids such as morphine and oxycodone, whose pharmacology are probably the best understood of any drug of abuse (they interact with mu opioid receptors [10]), have different behavioral and neurobiological effects that may affect addictions to the individual drugs (see my blog post). In a paper published by the lab I work for, the Kreek lab, cocaine administration in drug naïve mice (mice that have never had cocaine in their system) results in a rapid release of dopamine [11]. In contrast, some studies show that self-administration of an opioid drug only increases dopamine in rats that have already been exposed to the drug and not naïve animals [10]. The differences in the dopamine profiles between cocaine and opioids obviously means that how these two drugs affect the brain is different and is drug-specific! These are just a few small examples demonstrating the scientific inaccuracy of lumping all addictions into one general category or making the false claim that addiction has “nothing to do with the drug” (just as reducing cancer to a single disease is entirely inaccurate and harmful for its treatment).

Q: In the case of any type of addiction, what’s going on in the brain? 

L: The main region of interest is the striatum, and the nucleus accumbens, which is a part of the striatum. That region is responsible for goal pursuit, and it’s been around since before mammals. When we are attracted to goals, that region becomes activated by cues that tell you that the goal is available, in response to a stimulus. So you feel attraction, excitement and anticipation in response to this stimulus, and then you keep going after it. The more you go after that stimulus, the more you activate the system and the more you build and then refine synaptic pathways within the system. 

The other part of the brain here that’s very important is the prefrontal cortex, which is involved in conscious, deliberate control — reflection, judgment and decision-making. Usually there’s a balance between the prefrontal cortex and the striatum, so that you don’t get carried away by your impulses. With all kinds of addictions — drugs, behavior, people — the prefrontal system becomes less involved in the behavior because the behavior is repeated so many times. It becomes automatic, like riding a bike. 

S: Dr. Lewis’s assessment is basically correct. The core of the reward circuit involves dopamine-releasing neurons of the ventral tegmental area (VTA) projecting to the nucleus accumbens (NAc; a part of the ventral striatum), which primarily drives motivated behavior and is involved in reinforcement of drug taking behavior. Conversely, the prefrontal cortex acts as a “stop” against this system and one model of addiction is the motivated-drive to seek the drug overpowers the “stop” signal from the prefrontal cortex. However, addiction is far more complex beyond just this basic system. Numerous other circuits and systems (hippocampus, amygdala, hypothalamus, just to name a few) are also involved and each individual drug or rewarding stimuli can affect these circuits in disparate ways [12].

Q: What would a scientifically informed approach to addiction look like? 

L: That’s a really hard question because the fact that we know what’s happening in the brain doesn’t mean that we know what to do about it. 

A lot of recent voices have emphasized that addiction tends to be a social problem. Often addicts are isolated; they very often have difficult backgrounds in terms of childhood trauma, stress, abuse or neglect — so they’re struggling with some degree of depression or anxiety — and then they are socially isolated, they don’t know how to make friends and they don’t know how to feel good without their addiction. 

S: As I’ve stated above, a scientifically informed approach to addiction treatment already exists but is not widely used. However, one day an addict will hopefully be able to consult with a medical doctor to receive appropriate medications specific to their addiction, which will be combined with individual counseling by a psychiatrist or psychologist and a specific cognitive behavioral therapy or other psychological/behavioral therapy. The combination of medications and psychological therapy administered by trained medical professionals will be the future of evidence-based addiction medicine. Development of additional medications and/or psychological therapies for future treatment absolutely requires solid scientific evidence supporting their efficacy, which includes use of randomized control trials,  prior to widespread implementation.

But to call addiction primarily a social problem once again ignores all the basic neuroscience research that shows the powerful effects drugs have on the brain. It also ignores the prominent effect of genetics and how, due to a random role of the dice, an individual’s risk of becoming an addict can drastically increase [2, 13]. Plus the opioid epidemic that is currently sweeping the nation effects nearly every strata of society regardless of socioeconomic status, age, gender or race, and therefore cannot be explained simply by the hypothesis that addicts are people that are socially isolated. Why someone starts using drugs in the first place and how exactly they progress from a casual drug user to an addict are incredibly complex questions that scientists all over the world are attempting to answer through rigorous research. Being socially isolated or experiencing childhood trauma may certainly be factors that eschew some people towards the development of addiction but are definitely not the only ones.

Q: So what can we do about that?

L: Other than certain drugs that can reduce withdrawal symptoms, there’s nothing much medicine can offer, so we have to turn to psychology, and psychology actually offers a fair bit. There’s cognitive behavioral therapy, motivational interviewing, dialectic behavioral therapy, and now there are mindfulness-based approaches, which I think are really exciting. 

There’s been good research from Sarah Bowen in Seattle [on Mindfulness-Based Relapse Prevention] showing that mindfulness practices can have a significant impact on people, even on people who are deeply addicted to opiates. 

S: This is a completely false statement: medications for treatment of addictions exist [14]! Once again, comprehensive systematic reviews of methadone and buprenorphine, two medications used for treatment of opioid cravings, have indisputably shown that these medications are effective at keeping addicts off of heroin compared to no medication [5, 6]. Furthermore, a number of other drugs are currently being explored for treatments to alcohol and cocaine addiction [15, 16]. Some people may consider methadone or buprenorphine replacing “one drug with another” but this is naïve view of how powerfully addictive opioid drugs can be and how use of these FDA-approved medications in combination with individual psychological counseling, can lead to gradual dose reduction and amelioration of cravings. Medication-assisted addiction treatment is designed to help addicts fight their craving so that they can live a normal life. With time, dose can be reduced and cravings can become less intense.

The study Dr. Lewis cites regarding mindfulness is well designed and intriguing. However, the study did not compare mindfulness-based approaches to medication-based approaches and is therefore incomplete [17]. Nevertheless, it is an interesting approach that may be able to be combined with medication-based treatment but definitely requires more research before its efficacy can be confirmed.

References

  1. Koob GF, Le Moal M. Addiction and the brain antireward system. Annual review of psychology. 2008;59:29-53.
  1. Kreek MJ, et al. Opiate addiction and cocaine addiction: underlying molecular neurobiology and genetics. The Journal of clinical investigation. 2012;122(10):3387-93.
  1. Kelley AE. Memory and addiction: shared neural circuitry and molecular mechanisms. Neuron. 2004;44(1):161-79.
  1. Tronson NC, Taylor JR. Addiction: a drug-induced disorder of memory reconsolidation. Current opinion in neurobiology. 2013;23(4):573-80.
  1. Mattick RP, et al. Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. The Cochrane database of systematic reviews. 2009(3):CD002209.
  1. Mattick RP, et al. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. The Cochrane database of systematic reviews. 2014;2:CD002207.
  1. Anderson P, et al. Effectiveness and cost-effectiveness of policies and programmes to reduce the harm caused by alcohol. Lancet. 2009;373(9682):2234-46.
  1. Hartung DM, et al. Extended-release naltrexone for alcohol and opioid dependence: a meta-analysis of healthcare utilization studies. Journal of substance abuse treatment. 2014;47(2):113-21.
  1. Badiani A, et al. Opiate versus psychostimulant addiction: the differences do matter. Nature reviews Neuroscience. 2011;12(11):685-700.
  1. Fields HL, Margolis EB. Understanding opioid reward. Trends in neurosciences. 2015;38(4):217-25.
  1. Zhang Y, et al. Effect of acute binge cocaine on levels of extracellular dopamine in the caudate putamen and nucleus accumbens in male C57BL/6J and 129/J mice. Brain research. 2001;923(1-2):172-7.
  1. Russo SJ, Nestler EJ. The brain reward circuitry in mood disorders. Nature reviews Neuroscience. 2013;14(9):609-25.
  1. Kreek MJ, et al. Genetic influences on impulsivity, risk taking, stress responsivity and vulnerability to drug abuse and addiction. Nature neuroscience. 2005;8(11):1450-7.
  1. Kreek MJ, et al. Pharmacotherapy of addictions. Nature reviews Drug discovery. 2002;1(9):710-26.
  1. Addolorato G, et al. Novel therapeutic strategies for alcohol and drug addiction: focus on GABA, ion channels and transcranial magnetic stimulation. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2012;37(1):163-77.
  1. Bidlack JM. Mixed kappa/mu partial opioid agonists as potential treatments for cocaine dependence. Advances in pharmacology. 2014;69:387-418.
  1. Bowen S, et al. Relative efficacy of mindfulness-based relapse prevention, standard relapse prevention, and treatment as usual for substance use disorders: a randomized clinical trial. JAMA psychiatry. 2014;71(5):547-56.

Important: CDC Releases Report on Heroin Epidemic

heroin syringe

On July 10, 2015 the Centers for Disease Control (CDC) released Morbidity and Mortality Weekly Report (MMWR) on the Heroin epidemic that is sweeping the United States. By the standard of the Internet, this is old news by now but I’m just getting around to writing about it. And the report identifies critical information the public—and public officials—need to be aware of so the more publicity the better.

Download a pdf of the full report or an abbreviated fact sheet

The news is dire.

The big finding from the report is that heroin use has increased overall by 63% between 2002 and 2013 and amongst virtually all demographics regardless of gender, ethnicity, or socioeconomic status.

Even more striking is heroin deaths have quadrupled between 2002-2013.

Nearly all heroin users have also used at least 1 other drug.

As confirmed by many other reports, abuse of prescription opioid painkillers increases your risk of heroin use 40X! And 45% of heroin users are also addicted to opioid pain medication.

The report offers several viable responses that should be taken to curb the heroin epidemic:

  • Prevent: prevent and reduce abuse of prescription opioid painkillers
  • Reduce: increase the availability of medication-assisted treatment (MAT), which combines proven, effective medications such as methadone and buprenorphine with counseling and behavioral therapies
  • Reverse: expand the use of the naloxone to prevent heroin overdose

Above all, increased education and awareness of the heroin epidemic and medications available to treat addiction (methadone, buprenorphine) and prevent overdoses (naloxone)

The report also argues that states must play a key role in addressing this epidemic through such measures as implementation/expansion of prescription drug monitoring programs, significantly increased availability and access to MAT and naloxone, improved educational programs, and other measures.

For more information see:

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6426a3.htm?s_cid=mm6426a3_w

http://www.cdc.gov/vitalsigns/heroin/

Methadone Maintenance Therapy Works-End of Story

helping hands (pixbay.com)

I hate to be condescending but how the scientific community perceives a phenomena and how the public at large perceive the exact same thing can be starkly different.

For example, there is still a debate over the scientific legitimacy of global warming and climate change. Of course, this flies in the face of reality. In the scientific community, there is no more doubt over climate change than there is over heliocentricity (the theory that states the Earth revolves around the Sun). Study after study comes to the came conclusion, the scientific evidence is overwhelmingly in favor. But I’m not writing to debate climate change.

The same type of dichotomy exists for replacement/maintenance therapies for addiction. Methadone and the related compound buprenorphine (Suboxone, one of its formulations) are still considered controversial or ineffective or “replacing one drug for another.”

(wikipedia.com)
Methadone pills. (wikipedia.com)

In brief, methadone is a compound that acts on the same target as heroin (the mu opioid receptor) but unlike heroin, it acts for a very long time (24hrs). Dr. Vincent Dole, a doctor at the Rockefeller University in New York, and his colleague, Dr. Marie Nyswander, had the brilliant idea of using this very long-acting opioid compound as a way of treating heroin addiction. Indeed, methadone has the advantage of not producing the intense, pleasurable high that heroin produces but is still effective at curbing cravings for heroin and eliminating withdrawal symptoms. Dole and Nyswander published their first study in 1967 and methadone has been an approved—and effective—treatment for heroin addiction worldwide ever since.

However, controversy over the use of methadone exists. Even the opening of a methadone clinic can incite protests. The persistence of negative attitudes towards methadone and the stigma against treating addiction as a medical disease has prevented addicts from receiving proven medical treatments that are effective at curbing cravings and actually keeping them off of heroin and in treatment programs.

So just for a moment, let’s suspend our preconceived notions about what methadone is or how it works and let’s just ask our selves two simple questions:

 Does methadone work?

Does methadone keep addicts off of heroin and in treatment?

The answer is a resounding YES!

 

Mattick JP et al. Methaodone. 2009 title

Many controlled, clinical studies have examined the effectiveness of methadone. But a comprehensive comparison of methadone versus control, non-medication based treatments has not been considered amongst the various studies.

Researchers at the Cochrane Library performed this type of comprehensive analysis. Data was considered from 14 unique, previous clinical studies conducted over the past 40 years. Researchers compared methadone treatment versus control, non-medication based treatment approaches (placebo medication, withdrawal or detoxification, drug-free rehabilitation clinics, no treatment, or waitlist).

11 studies and 1,969 subjects were included in their final analysis.

 Read the full paper, published in 2009, here.

The results were clear. Methadone was found to keep people off of heroin and in treatment more effectively than control treatments. Urine analysis confirmed methadone-treated addicts were more likely to be heroin-free and regularly seeking treatment.

Of course, as I stated above, this is nothing new. But it’s important to note that abstinence therapies or treatments that encourage addicts to go “cold turkey” don’t really work; inevitably, relapse will occur. A medical treatment exists to help addicts fight their cravings so their brains are not fixated on obtaining heroin and these people are able to regain normal daily functions. And in time, methadone doses can be tapered down as intensity and frequency of cravings decrease.

The debate now should not be on whether methadone works, but on how to use it effectively and how to expand its use so that as many people as possible can benefit from it.

Most importantly, methadone helps an addict to return to normal life. End of story.

New Review Paper-The Prescription Opioid and Heroin Epidemic

(Image by Mark Weiss/Corbis)
(Image by Mark Weiss/Corbis)

A new paper published online in January 2015 by Kolodny et al. provides an overview of the epidemic of addiction to opioid prescription medications and heroin which is sweeping through the United States. Numerous news outlets from the Huffington Post to the New York Times have been covering this disturbing trend. This important review paper is being released at a critical time.

Kolodny et al TitleYou can find the complete article here.

The authors do an excellent job of outlining the epidemic from a public health perspective. I just wanted to summarize some of the paper’s main points and findings:

  • Abuse of prescription opioid pain relievers (OPR) and heroin is reaching epidemic levels
    • From 1999-2011, oxycodone (a common OPR) use has increased by 500%
    • From 1997-2011, there has been a 900% increase in individuals seeking treatment to for opioid addiction
    • From 2004-2011, there has been a doubling in ER visits due to non-medical use of OPR
    • The author’s highlight that there is a disturbing correlation between the rise in opioid sales, opioid overdose deaths, and opioid addiction (See the figure below)
(Figure 1 from Kolodny et al. 2015)
(Figure 1 from Kolodny et al. 2015)
  • The authors contend that the cause of our current epidemic is rooted in:
    • The development of new opioid medications such as OxyContin (an extended release form of oxycodone introduced in 1995)
    • The over-prescription of OPR coupled with a shift in medical attitudes towards the treatment of chronic pain
    • A series of studies suggesting that long-term opioid use does not result in addiction. We now know this to be false.
      • According to a recent study, 25% of chronic pain patients treated with OPR fit criteria for opioid addiction and 35% for opioid abuse disorder
  • The public health issues related to non-medical use of OPR are significant
    • Heroin use has drastically increased over the same period as OPR abuse
    • 4 out of 5 current heroin users report that their addiction began with abuse of OPR (See here for more information).
    • Overdose deaths and hospitalizations as a result of OPR have been strikingly high since 2002. See the graphs below.
(Figure 4 from Kolodny et al. 2015)
(Figure 4 from Kolodny et al. 2015)
  • Using an epidemiologic approach, the authors outline a prevention strategy for opioid addiction broken down into primary, secondary, and tertiary interventions.
    • Primary prevention
      • Reduce the incidence of the disease condition: opioid addiction (ie prevent new addiction cases)
      • Education of prescribers regarding OPR use
        • The risks of chronic OPR use, such as addiction and respiratory depression (difficulty breathing), are high
        • Little data exists for the effectiveness of long-term OPR use in helping chronic pain patients
      • Substitution of OPR for non-opioid pain relievers must be strongly encouraged
      • Prevention of OPR use amongst adolescents
        • Caution in OPR prescribing
          • Most youths that experiment with them get OPR from family or friends who have an OPR prescription
        • Change the perception that OPR use is less risky than heroin use
          • In reality the risk of addiction to OPR is as high as it is for heroin
    • Secondary Prevention
      • Identify and treat opioid addicts early in their disease
        • Identify users of OPR that are detected by prior to more significant health problems or transition to heroin use
        • Difficulty in diagnosing opioid addiction
          • Urine toxicology screens in some cases
          • Use of prescription drug monitoring programs (PDMPs) to identify patients who seek prescriptions from multiple doctors
    • Tertiary prevention
      • Treatment and rehabilitation of opioid addiction
        • The National Survey on Drug Use and Health (NSDUH) estimates 2.1 million Americans are addicted to OPR and 467,000 to heroin.
        • Combination of pharmacologic and psychosocial treatments
          • Psychosocial therapies (residential treatment centers, mutual-help programs, 12-step programs) can be effective for some patients but should be use in combination with pharmacologic treaments
        • Pharmacologic treatments such as methadone and buprenorphine (Suboxone) are safe and highly effective
          • They work by effectively blocking cravings without causing the “high” the OPR and heroin cause
          • However, fewer than 1 million addicts are receiving these treatments
          • Significant federal limitations exist to buprenorphine prescription
            • See my Post on this topic, which links to an important Huffington Post article on the topic
        • Harm-reduction approaches
          • Needle-exchange programs to reduce HIV transmission
          • Naloxone for treatment of overdose deaths
    • Conclusions
      • Prescription opioid and heroin addiction are reaching epidemic levels in the United States
      • A coordinated public health effort of federal and state agencies, health care providers and insurers, treatment/recovery initiatives and the research community is required to deal with this crisis.

For more statistical information, consult the National Survey on Drug Use and Health.

Also, see the data section of the Substance Abuse and Mental Health Services (SAMSHA) for statistics related to non-medical use of OPR and heroin.