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

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The CDC Fights Back Against the Opioid Epidemic

2000px-US_CDC_logo.svg

The CDC has released important information on dealing with the prescription opioid pain medication and heroin epidemic. Opioids are a class of drugs that include pain medications such as morphine, oxycodone, hydrocodone, methadone, fentanyl and others and the illegal drug heroin. I’ve spoken a great deal about this problem in various other posts (see here here here and especially here and here). Just to summarize some of most disturbing trends: the US is experiencing a surge in deaths due to overdose on opioids (overdoses/year due to opioids are now greater than fatalities from car crashes), virtually all demographics (age groups, income levels, gender, race) are affected, and many people addicted to opioid pain pills transition to heroin and as such, a huge increase in heroin abuse is also occurring; teenagers and adolescents are especially hard hit. The CDC’s report, released on Friday, March 18 provides a thorough review of the clinical evidence around prescription opioid pain medications and makes 12 recommendations to help control the over-prescription of these powerful drugs in attempt to reduce the amount of overdose deaths and addiction.

Read the full report.

I finally got around to reading the whole thing and am happy to summarize its main analyses and findings. While the report is intended for primary health care providers and clinicians, the report’s findings are important for anyone suffering from short or long-term pain and the risks vs benefits posed by opioids.

But before I dive into the meat of the report, I wanted to clarify an important issue about addiction to prescription opioids. A false narrative exists that those suffering from addiction are “drug seekers” and it is this group of people that is duping doctors in prescribing them too many opioids while good patients that take opioids as directed are not over dosing or becoming addicted. It’s important to remember that opioids are so powerful anyone that takes them runs the risk of overdosing or becoming addicted after repeated use. Most people suffering from addiction and overdoses during the current prescription opioid epidemic are people that used opioids medically and not for recreation. This is true for youths prescribed opioids for a high-school sports injury, and older patients prescribed opioids for chronic back pain, and many other “regular” people. The CDC released this report to help fight back against the over-prescription of opioids and the severe risks that accompany their use. Doctors and patients alike need to be aware of the risks vs benefits of opioids if they decide to use them for pain therapy.

Hydrocodone (wikimedia.org)
Hydrocodone (wikimedia.org)

The CDC’s report had three primary goals:

  1. Identify relevant clinical questions related to prescribing of opioid pain medications.
  2. Evaluate the clinical and contextual evidence that addresses these questions
  3. Prepare recommendations based on the evidence.

Two types of evidence were used in preparation of the report: direct clinical evidence and indirect evidence that supports various aspects of the clinical evidence (contextual evidence). Studies included in the analysis ranged from high quality randomized control studies (the gold standard for evaluating clinical effectiveness) to more observational studies (not strong, direct evidence but useful information nonetheless).

The report identified five central questions regarding the concerns over opioids:

  1. Is there evidence of effectiveness of opioid therapy in long-term treatment of chronic pain?
  2. What are the risks of opioids?
  3. What differences in effectiveness between different dosing strategies (immediate release versus long-acting/extended release)?
  4. How effective are the existing systems for predicting the risks of opioids (overdose, addiction, abuse or misuse) and assessing those risks in patients?
  5. What is the effect of prescribing opioids for acute pain on long-term use?

Based on a close examination of the clinical evidence from a number of published studies, the CDC found the following answer to these questions.

  1. There is no evidence supporting the benefits of opioids at managing chronic pain. Opioids are only useful for acute (less than 3 days) pain and for cancer pain or end-or-life pain treatment.
  2. Opioids have numerous risks such as abuse and addiction, overdose, fractures due to falling in some older patients, car crashes due to impairments, and other problems. The longer opioids are used the greater these risks.
  3. There is no difference in effectiveness between immediate release opioids and long-acting or extended release formulation. The evidence suggests the risk for overdose is greater with long-acting and extended-release opioids.
  4. No currently available monitoring methods or systems are capable of completely predicting or identifying risk for overdose, dependence, abuse, or addiction but severak methods may be effective at helping to evaluate these risk factors.
  5. The use of opioids for treating acute pain increases the likelihood that they will be sued long-term (most likely because of tolerance and dependence).
Oxycodone (wikimedia.org)
Oxycodone (wikimedia.org)

The CDC also examined what they called contextual evidence or studies that didn’t directly answer the primary clinical questions but still provided valuable, if indirect, information about treatment of pain with/without opioids.

  • Non-medication based therapies like physical therapy, exercise therapy, psychological therapies, etc. can be effective at treating chronic pain for a number of conditions.
  • Non-opioid pain medications such as acetaminophen, NSAIDs, Cox-2 inhibitors, anti-convulsants, and anti-depressants (in some instances) were also effective in treating chronic pain for various conditions and have fewer dangers than opioids.
  • Long-acting opioids increase the risk for overdose and addiction. Higher doses of opioids also increase the risk for overdose.
  • Co-prescription of opioids with benzodiazepines greatly increases the risk of overdoses.
  • Many doctors are unsure of how to talk to their patients about opioids and their benefits vs risks and most patients don’t know what opioids even are.
  • The opioid epidemic costs billions of dollars in medical and associated costs. Its estimated  costs due to treatment of overdose alone is $20.4 billion.

Many other findings and important pieces are information were reported but too many to list here.

Based on all results of the analysis the CDC came up with 12 recommendations in three broad categories. I’ll briefly discuss each recommendation.

Category 1: Determining when to initiate or continue opioids for chronic pain.

  • Recommendation 1: Non-pharmacologic (medication-based) therapy and non-opioid pharmacologic therapy are preferred for chronic pain.
    • The risks of overdose and addiction from long-term use of opioids is very high and benefits for actually treating pain are very low for most people. Therefore, other safer and more-effective treatments should be use first. The discussion of the risks vs benefits needs to be made clear by the patient’s doctor.
  • Recommendation 2: Before starting opioid therapy for chronic pain, clinicians should establish treatment goals with all patients, including realistic goals for pain and function
    • Opioids should be used for the shortest amount of time possible but if used for a long-term treatment, at the lowest effective dose.
    • If a patient suffers from an overdose or seems as if dependence or addiction is developing, a patient may need to be tapered off of opioids.
  • Recommendation 3: Before starting and periodically during opioid therapy, clinicians should discuss with patients known risks and realistic benefits of opioid therapy.
    • The risks are high for the use of opioids and it is necessary for doctors to keep their patients informed about these risks.
    • Doctors should be “be explicit and realistic about expected benefits from opioids, explaining that while opioids can reduce pain during short-term use, there is no good evidence that opioids improve pain or function with long-term use, and that complete relief of pain is unlikely.”

Category 2: Opioid selection, dosage, duration, follow-up, and discontinuation.

  • Recommendation 4: When starting opioid therapy, clinicians should prescribe immediate-release opioids instead of extended-release or long-acting opioids.
    • There appears to be no difference in effectiveness at treating pain between the different types of opioids but the long-acting opioids come with a greater risk for overdose and dependence.
    • Long-acting opioids should be reserved for cancer pain or end-of-life pain.
    • It’s important to note that “abuse-deterrent” does not mean that there is no risk for abuse, dependence, or addiction. These types of formulations are generally to prevent intravenous use (shooting up with a needle) but most problems with opioids occur as a result of normal, oral use.
  • Recommendation 5: When opioids are started, clinicians should prescribe the lowest effective dosage.
    • The higher the dose the greater the risk. A low dose may be sufficient to control the pain without risk for overdose or the development of dependence.
    • Opioids are often most effective in the short-term and may not need to be continued after 3 days.
    • If dosage needs to be increased, changes in pain and function in the patient should be re-evaluated afterwards to determine if a benefit has occurred.
    • Patients currently on high-dose long-term opioids for chronic pain may want to consider tapering down their dosage.
      • Tapering opioids can be challenging can take a long-time due to the physical and psychological dependence. Tapering should be done slowly to and the best course of dosage should be determined specifically for the patient.
    • Recommendation 6: Long-term opioid use often begins with treatment of acute pain. When opioids are used for acute pain, clinicians should prescribe the lowest effective dose of immediate-release opioids and should prescribe no greater quantity than needed.
      • Evidence suggests that using an opioid for acute pain can start a patient down a path of long-term use. This should attempted to be avoided by using a low dose if opioid is selected to treat acute pain.
      • Acute pain can often be effectively managed without opioids with non-medication-based therapies (like exercise, water aerobics, physical therapy, etc.) or non-opioid medications (like acetaminophen or NSAIDs).
    • Recommendation 7: Clinicians should evaluate benefits and harms with patients within 1-4 weeks of starting opioid therapy for chronic pain or of dose escalation.
      • Opioids are most effective for the first three days and possible up to a week. If long-term therapy is decided upon, treatment should regularly be reassessed and reevaluated (at least every 3 months for long-term therapy).

Category 3: Assessing risks and addressing harms of opioid use.

  • Recommendation 8: Before starting and periodically during continuation of opioid therapy, clinicians should evaluate risk factors for opioid-related harms. Clinicians should incorporate into the management plan strategies to mitigate risk, including considering offering naloxone.
    • Specific risk factors for the specific condition that patient is using opioids for should be considered when developing the treatment plan.
    • Naloxone blocks the effects of opioids and can immediately revive someone that has experienced an overdose. Naloxone should be offered to patients if a patient is using opioids at high-dose for long-term therapy or previously suffered an overdose.
  • Recommendation 9: Clinicians should review the patient’s history of controlled substance prescription using state prescription drug monitoring program (PDMP) data to determine whether a patient is receive opioid dosages or dangerous combinations that put him or her at risk for overdose.
    • PDMPs are state-run databases that collect information on controlled prescription drugs dispensed by pharmacies and in some states, physicians too.
    • While the clinical evidence was unclear if PDMPs were accurate at predicting overdose or addiction, the contextual evidence supported that “most fatal overdoses were associated with patients receiving opioids from multiple prescribers and/or with patients receiving high total daily opioid dosage.”
    • PDMP should be consulted before beginning opioid therapy and during the course of treatment if used for long-term therapy and this data should be discussed with the patient.
    • However, PDMP data must be used cautiously as some patients are turned away from treatment that would otherwise have benefited.
  • Recommendation 10: (not a general recommendation but to be considered on a patient-by-patient basis) When prescribing opioids for chronic pain, clinicians should use urine drug testing before starting opioid therapy and consider urine drug testing at least annually to assess for prescribed medications as well as other controlled prescription drugs and illicit drugs.
    • Urine drug tests can reveal information about potential risks due to combinations with other drugs not reported by the patient (e.g. benzodiazepines, heroin).
    • Urine testing should become standard practice and should be done prior to starting opioids for chronic therapy.
    • Clinicians should make it clear that testing is intended for patient safety and is not intended to deprive the patient of therapy unnecessarily.
  • Recommendation 11: Clinicians should avoid prescribing opioid pain medication and benzodiazepines concurrently whenever possible.
    • Strong evidence suggests that many overdoses occurred in patients prescribed both benzodiazepines and opioids. The two should never be prescribed together if at all possible.
  • Recommendation 12: Clinicians should offer or arrange evidence-based treatment (usually medication-assisted treatment with buprenorphine or methadone in combination with behavioral therapies) for patients with opioid abuse disorder (addiction).
    • Many patients using opioids for chronic pain now may have become physically and psychologically addicted to them and should be offered treatment (estimated at 3-26% of patients using opioids for chronic pain therapy).
    • Methadone and buprenorphine are proven, safe, and effective-treatments that retain patients in treatment and that satisfy an opioid addict’s cravings, prevent relapse to abusing opioids/heroin, and allow the patient to live a normal life (read my blog post on methadone).
    • Behavioral therapy/individual counseling in combination with medication-based treatment may improve positive benefits of treatment even further.
    • However, access to these medications can be extremely limited in some communities due to availability (methadone is restricted to clinics and clinicians need certification in order to prescribe buprenorphine) or cost (treatment often is not covered by insurance).
    • Urine testing or PDMP data may help to reveal if a patient has become addicted and if so, treatment should be arranged.

In Summary, the main takeaways from the report are:

  • Opioids are associated with many risks such as overdose, abuse, dependence, addiction, and others (e.g. fractures from falling or car-crashes due to impairment).
  • No evidence exists that opioids are effective for treatment of chronic pain (with the exception of cancer and end-of-life pain).
  • Opioids are most effective for short term (3-7 days) and in immediate-release formulations.
  • Non-medication based therapies and non-opioid medications are preferred for treatment of chronic pain.
  • Doctors need to clearly explain the risks vs benefits of opioid therapy with their patients.
  • If decided as the best course of action for a particular patient, opioid therapy needs to be repeated re-evaluated to make sure it is still working to alleviate pain.
  • The prescription drug monitoring programs are useful tools that should be consulted prior to beginning therapy in order to help determine a patient’s history with opioids and risk for abuse or overdose.
  • Naloxone should be made available to patients using opioids for long-term therapy in order to prevent possible overdoses.
  • Access to medication-based treatments (methadone or buprenorphine) for dependent individuals should be provided.

Concluding Thoughts

In 1995 Purdue pharmaceuticals released OxyContin (oxycodone, one of the most common prescription opioid pain medications) and launched an enormous push for doctors to use opioids as the primary treatment for chronic pain. The enormous surge in in prescriptions of oxycodone (500% increase from 1999-2011) followed this marketing campaign. One of the most disturbing aspects revealed by the CDC’s report is that despite this surge in prescriptions, there is a complete lack of data on the effectiveness of opioids for long-term chronic pain therapy.

To be fair though, “Big Pharma” is not the sole culprit in this crisis. One argument is that pharma was responding to the need of clinicians for an increased demand by patients for management of chronic pain. It is very disturbing though that the push for the use of opioids for long-term management was initiated without any supporting evidence. This is another example of how medicine must be guided by evidence-based principles and not on personal beliefs and values or medical tradition and culture.

It’s important to remember that some patients do tolerate opioids well and these patients may find them beneficial at treating their chronic pain condition. The guidelines do stress frequent reevaluation of the benefits vs risks of opioids and for some patients benefits will outweigh the risks.

Finally, the CDC’s guidelines are not legally binding. These are recommendations and not laws or regulations. This means no doctors are not legally required to comply with any of the CDC’s recommendations. Hopefully some or all of these recommendations will be formalized into formal laws and regulations because many of them are extremely important in regulating these powerful and potentially dangerous drugs.

(Also check out the Diane Rehm Show’s hour-long discussion of the report. As usual, the show offers a high quality analysis and discussion from a panel of experts.)

Top Scientific Leaders on Addiction Call for its Treatment as a Medical Disease

(© Alan Cleaver flickr https://www.flickr.com/photos/alancleaver/4104954991)
(© Alan Cleaver flickr https://www.flickr.com/photos/alancleaver/4104954991)

A new review article published in the prestigious New England Journal of Medicine highlights the importance of treatment of addiction as a medical disease and calls for a change in public health policy towards addiction. Written by several leaders in the addiction field including Nora Volkow, MD, the director of NIDA, and George Koob, PhD, the director of NIAAA, the article does a superb job at outlining the underlying biology of addiction and clearly explains why addiction is a disease of the brain that needs to be treated medically.

Read the full article here.

In fact, I also covered most of the points made in the article in my own post for Addiction Blog on “Why Addiction is a Brain Disease?”

However, when it comes to public health policy towards addiction, this is where the article fell short. While treatments for opioid addiction such as methadone and buprenorphine were briefly mentioned in the article, there was no call for a national effort to be made to increase access to these vital medications. The authors had a potential to increase awareness of the opioid epidemic and the treatments already on hand to fight it but failed to make a stronger case for this critical improvement.

Nevertheless, the article is well written and a great introduction to the neuroscience of addiction and why it is a disease of the brain.

Why is Addiction a Brain Disease?

I started as a contributor for the blog network addictionblog.org.

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Read my first post, published today!

WHY IS ADDICTION A BRAIN DISEASE?

Promising Shifts in Policy Towards Addiction Prevention and Treament

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

 

Normally a search for drug addiction in Google news pulls up a similar thread of articles: arrests of dealers and addicts, big drug busts, a crime committed by a user or dealer, somebodies mug shot. Basically, the news tends to cover only the drug enforcement and criminal aspects of the drug addiction problem. This is unsurprising since for the past few decades the lens in which we view addicts and addiction has been smeared by the “War on Drugs”, which views drug users as criminals and deviants and seeks to punish rather than treat. However, with advances in medical technology, advances in neuroscience, cognitive psychology, and a host of related fields, we understand addiction at the neurochemical and physiological level better than we ever have before. A shift in attitude that acknowledges addiction as a medical disease that needs to be treated as such (well established in the scientific community) is finally making its way into public consciousness, and most importantly, public policy.

SFN 2015 LogoI was recently at the 2015 Society for Neuroscience Conference, an enormous gathering of neuroscientist from around the world, held Oct 17-21 in Chicago. The conference hosts an overwhelming number of lectures, symposia, and workshops for scientists to share the latest developments in research in Alzheimer’s, Parkinson’s, stroke, learning and memory, brain development, addiction, and many others neuroscience sub-disciplines. Several special lectures on neuroscience related-topics are also held and I had the pleasure of attending one of these special lectures given by the Honorable Jed S. Rakoff, Senior US District Judge for the Southern District of New York and founding member of the MacArthur Foundation Project on Law and Neuroscience, which researches issues on the intersection of law and neuroscience. Judge Rakoff spoke on how new advances in neuroscience research such as improved neuroimaging technologies and greater understanding into human cognition and decision-making, is changing how the law treats defendants. Significantly, Judge Rakoff spoke frequently about addiction, and he acknowledges what many do, that those arrested for non-violent offenses should be treated, not brutalized. However, he explained that many judge’s hands are tied when it comes to sentencing due to laws in place that set mandatory minimums for drug offenders. Judge Rakoff believes these mandatory minimum laws should be eliminated if progress is to be made toward providing treatment, rather than prison sentences, for drug addicts. It was refreshing to hear this come from such a distinguished judge and I hope it is a bellwether for changes in our legal system.

Of course, laws cannot changes without lawmakers to change them. But we may be seeing the beginning of shift in drug addiction policy for the first time in years.

The epidemic of addiction to prescription opioids and heroin has been making news for months now. I’ve blogged about this epidemic in several posts. One covering a review article describing the epidemic, another sharing an excellent article in the Huffington Post about the epidemic and available treatments for opioid addiction, and most recently, an important report released by the Centers for Disease Control that names opioid addiction as one of the counties top public health crises. Following this latter groundbreaking report by the CDC, policy-makers are finally starting to wake up to the problem.

In a speech in on October 21 in Charleston, West Virginia, one of the areas in the country worst hit by the opioid problem, President Obama held an hour-long public forum in which he promised $133 million dollars to combating the prescription opioid and heroin problem. The President gave about a 15-minute introduction to the event, which entailed some of the most refreshing comments about addiction to ever come from a US President.

Watch the full speech here:

President Obama began by citing shocking statistics stated in the CDC report concerning the surge in deaths due to prescription opioids, “More Americans now die from drug overdoses than from motor vehicle crashes…The majority involve legal prescription drugs.” He went on to talk about heroin as an extension of prescription opioid abuse, “4 out of 5 heroin users start with prescription opioids”.

Of special significance was the shift in language he used to describe addiction and addicts, which contrasts strongly with the “War on Drugs” rhetoric of the previous administration. Obama said, “This is an illness and we have to treat is as such. We have to change our mindset”, which is something that scientists have been arguing for years but is just now being acknowledged by a US President.

Progress towards treating addiction cannot be made unless the biological and medical realities of the illness are understood and addicts are treated as patients rather than criminals. Indeed, stigma towards addicts is one of the biggest hurdles towards reforming public health policy and attitudes towards addiction and President Obama admitted this, “We can’t fight this epidemic without eliminating stigma.”

Some progress has been made under Obama’s watch and he and Health and Human Services Secretary Sylvia Burwell outlined several addiction reforms. One important change already in place is a stipulation of the Affordable Care Act that requires insurance to cover treatment for substance abuse disorders. Secretary Burwell outlined three points at the forum in West Virgina for an “evidence-based strategy” towards addiction prevention and treatment:

  • Point 1: Changing prescribing practices. This is necessary to stem the over prescription of opioids and the dependence to the drugs that develops in some patients as result.
  • Point 2: Expand medication-assisted treatment programs and to make sure patients can have access to treatment and behavioral counseling that can help them.
  • Point 3: Increased access to naloxone. Naloxone counteracts the effects of opioids and should be a standard medication on hand for any first responder that deals with overdoses.

The details about implementing these strategies were not provided though.

However, Obama’s speech may be coming too late, as Dr. Andrew Kolodny, founder of the Phoenix House Treatment facilities in New York, believes. As reported in New York Times, Dr. Kolodyn is disappointed with Obama’s progress and thinks he has waited too long to take action and says that opioid epidemic problem has gotten considerably worse over under Obama’s watch.

I am anxious to see what changes may occur within the last year of Obama’s presidency in respect to the opioid epidemic. However, if more permanent changes are not made in the law, a conservative Republican president could easily over turn any changes made and revert to a failed Reagan-era “War on Drugs” approach.

The Genetic Link Between Creativity and Psychiatric Disease

(www.wikipedia.org)
(www.wikipedia.org)

The biological sciences are in a golden era: the number of advanced technological tools available coupled with innovations in experimental design has led to an unprecedented and accelerating surge in knowledge (at least as far as the number of papers published is concerned). For the first time in history, we are beginning to ask questions in biology that were previously unanswerable.

No field demonstrates this better than genetics, the study of DNA and our genes. With the advent of high-throughput DNA sequencing, genetic information can be acquired literally from thousands of individuals and even more remarkably, can be analyzed in a meaningful way. Genomics, or the study of the complete set of an organism’s DNA or its genome, directly applies these advances to probe answers to questions that are literally thousands of years old.

A recent study, a collaborative effort from scientists in Iceland, the Netherlands, Sweden, the UK, and the US, is an example of power of genomics and to answer these elusive questions.

Power eet al. Nat. Neursci. 2015. Title

The scientists posed an intriguing question: if you are at risk for a psychiatric disorder, are you more likely to be creative? Is there a link between madness and creativity?

Self-portrait with bandaged ear. Vincent van Gogh, 1889. (wikipedia.org)
Self-portrait with bandaged ear. Vincent van Gogh, 1889. (wikipedia.org)

Aristotle himself once said, “no great genius was without a mixture of insanity” and indeed, the “mad genius” archetype has long pervaded our collective consciousness. But Vincent Van Gogh cutting off his own ear or Beethoven’s erratic fits of rage are compelling stories but can hardly be considered empirical, scientific evidence.

But numerous studies have provided some evidence that suggests a correlation between psychiatric disorders and creativity but never before has an analysis of this magnitude been performed.

Genome-wide association studies (GWAS) take advantage of not only the plethora of human DNA sequencing data but also the computational power to compare it all. Quite literally, the DNA of thousands of individuals is lined up and, using advance computer algorithms, is compared. This comparison helps to reveal if specific changes in DNA, or genetic variants, are more common in individuals with a certain trait. This analysis is especially useful in identifying genetic variants that may be responsible for highly complex diseases that may not be caused by only a single gene or single genetic variant, but are polygenic, or caused by many different genetic variants. Psychiatric diseases are polygenic, thus GWAS is useful in revealing important genetic information about them.

This video features Francis Collins, the former head of the Human Genome Project and current director of the National Institutes of Health (NIH), explaining GWAS studies. The video is 5 years old but the concept is still the same (there’s not many GWAS videos meant for a lay audience).

The authors used data from two huge analyses that previously performed GWAS on individuals with either bipolar disorder or schizophrenia compared to normal controls. Using these prior studies, the author’s generated a polygenic risk score for bipolar disorder and for schizophrenia. This means that based on these enormous data sets, they were able to identify genetic variants that would predict if a normal individual is more likely to develop bipolar disorder or schizophrenia. The author’s then tested their polygenic risk scores on 86,292 individuals from the general population of Iceland and success! The polygenic risk scores did associate with the occurrence of bipolar disorder or schizophrenia.

Next, the scientists tested for an association between the polygenic risk scores and creativity. Of course, creativity is a difficult thing to define scientifically. The authors explain, “a creative person is most often considered one who take novel approaches requiring cognitive processes that are different from prevailing modes of thought.” Translation: they define creativity as someone who often thinks outside the box.

In order to measure creativity, the authors defined creative individuals as “belonging to the national artistic societies of actors, dancers, musicians, and visual artists, and writers.”

The scientists found that the polygenic risk scores for bipolar disorder and schizophrenia each separately associated with creativity while five other types of professions were not associated with the risk scores. An individual at risk for bipolar disorder or schizophrenia is more likely to be in creative profession than someone in a non-creative profession.

 The authors then compared a number of other analyses to see if this effect was due to other factors such as number of years in school or having a university degree but this did not alter the associations with being in a creative field.

Finally, the same type of analysis was done with two other data sets: 18,452 individuals from the Netherlands and 8,893 individuals from Sweden. Creativity was assessed slightly differently. Once again creative profession was used but also data from a Creative Achievement Questionnaire (CAQ), which reported achievements in the creative fields described above, was available for a subset of the individuals.

Once again, the polygenic risk scores associated with being in a creative profession to a similar degree as the Icelandic data set; a similar association was found with the CAQ score.

The authors conclude that the risk for a psychiatric disorder is associated with creativity, which provides concrete scientific evidence for Aristotle’s observation all those years ago.

However, future analyses will have to broaden the definition of creativity beyond just narrowly defined “creative” professions. For example, the design of scientific experiments involves a great deal of creativity but is not considered a creative profession and is therefore not included in these analyses, and a similar argument could be made with other professions. Also, no information about which genetic variants are involved or what their function is was discussed.

Nevertheless, this exciting data is an example of the power that huge genomic data sets can have in answering fascinating questions about the genetic basis of human behavior and complex traits.

For further discussion, read the News and Views article, a scientific discussion of the paper, which talks about potential evolutionary mechanisms to explain these associations.

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.

Childhood Abuse Has Long-lasting Effects on Brain Function

(© Derek Simon 2015)
(© Derek Simon 2015)

 

Why is it that one person becomes an addict and another does not?

This is a central question in addiction field and one that I’ve touched on in some of my posts (and will continue to explore in the future). Two recent papers may help to shed more light on this difficult and complicated question. Both studies have revealed changes that occur in the brain as a result of childhood trauma that may cause an individual to be more susceptible to risky behavior such as drug abuse.

Both papers are neuroimaging studies meaning they use living human subjects and look at brain activity in response to different scenarios. There are many ways to image a living brain but these studies both use functional magnetic resonance imaging (fMRI). Basically, fMRI measures blood flow into the brain. As neurons turn “on” (that is, when they conduct an electrical signal), they require energy. Neurons use glucose as their primary energy source, which is delivered to them through blood flow. Therefore, the more blood flowing to a region of the brain = the more energy required by neurons = more neurons “firing”.

 The analysis of fMRI data is very complicated and beyond the scope of my knowledge or this discussion. But in essence, when you think or read about something, certain areas of your brain process that information. Using fMRI, you can actually visualize regions of the brain that are turning “on” or “off” when a patient thinks about a particular situation! Watch these YouTube videos for additional explanations on fMRI.

 

fMRI Image (wikipedia.org)
fMRI Image (wikipedia.org)

In both of the studies featured in today’s post, subjects would read different scripts while in the fMRI scanner and the scientists would image the entire brain and identify the regions that were active during the test. Then data from multiple subjects can be compiled and a composite image that represents the averages all the subjects can be produced. The picture to the right is an example of this type of composite image. Finally, you can see which regions of the brain are active for most of the patients during the different experiments. Keep this information in mind as I go over the papers.

Elsey et al. Neuropsychopharm. 2015

The first paper performed fMRI scans on adolescents that had or had not experienced maltreatment or trauma during childhood (less than 18 years old). 67 subjects were recruited from a larger study looking at disadvantaged youth and 64 were eventually used in the study. The adolescents filled out a standard survey that allowed the scientists to learn which of the subjects had experienced maltreatment/trauma during childhood.

The experiment involved having the different subjects read a script about either a stressful moment, their favorite food, or something neutral or relaxing while their brains were being imaged in the fMRI scanner.

Amazingly, for the stressful scenario, a difference in brain activity was detected in multiple regions of the prefrontal cortex only in subjects that had experienced childhood maltreatment! What this means is those youths that were abused as kids responded to stress differently than youths that were not abused. Their brain function has literally been changed later in life as a result of the abuse they suffered as children.

 The prefrontal cortex is a part of the mesocorticolimbic system, a group of brain areas especially involved in addiction. The prefrontal cortex is also involved in decision making, impulsivity, and other functions. It’s not clear what this change in prefrontal cortex activity actually means but it is possible that the altered activity could make the youth more vulnerable to stress or more likely to engage in risky activities, such as drug abuse.

 Elton et al. Addiction Biol. 2014

The second study was also interested in subjects that had experienced maltreatment or trauma during childhood but it instead of adolescents, this study used subjects that are adult men dependent on cocaine. Similarly, the subjects were grouped into those that had been mistreated as kids and those that had not.

In a parallel design to the other study, the subjects read a script describing a situation while being scanned in the fMRI machine. The scripts in this study included stress, cocaine-associated, and neutral. Interestingly, an increase in activity in a specific region of the prefrontal cortex and an area of the brain involved in motor activity were detected in the subjects that had been abused during childhood. And even more important, these changes were correlated to enhanced drug craving. These results suggest that childhood trauma can affect drug craving for addicts, which may be relevant factor in triggering relapse. That is to say, addicts that have been abused as children may be more vulnerable to not only acquiring addiction but also relapse.

 It is important to keep in mind that, like the previous study, the real functional importance of these different changes in unknown. However, clearly there are real changes that occur in the brain as a result of abuse/maltreatment during childhood. Imaging data must be taken with a grain of salt because it is difficult to show real causality. Yet, both studies (and many others) suggest long-lasting changes in brain activity, especially in response to stress, as a result of childhood trauma/maltreatment.

The conclusions we can draw from these studies is that childhood mistreatment, or trauma can have lasting changes on the brain. How these changes affect behavior is a much more difficult question to answer. Nevertheless, the changes that occur may be one of the factors that can contribute to susceptibility to addiction. These studies are supported by a previous post in which animal studies have shown that stress during early age leads to greater drug use as an adult.

And a broader point, these two neuroimaging studies help to put a different perspective on disadvantaged youth and importance of a stable home life, the lack of which can significantly affect you as an adult and may even contribute to susceptibility of become a drug addict.

New York City’s Failure to Care for Recovering Addicts

(From wikipedia.com)
(From wikipedia.com)

A new investigative report in the New York Times reveals a corrupt and virtually unregulated system of housing that preys on those that suffer from addiction and mental disease. Called “three-quarter” homes, there may be as many as 600 of these privately owned residences in NYC that act as a limbo between inpatient hospital care and shelters. The article tells the story of a group of homes owned by a single landlord and a few of the unfortunate residents trapped within this system. Disturbingly, reputable hospitals and treatment centers often refer patients to these homes. Landlord’s profit off of their tenant’s state-provided subsidies, which are insufficient for any other type of housing. The landlord collects the government assistance checks provided to the tenants provided that they regularly attend treatment centers. This has the unexpected consequence of incentivizing a landlord to encourage his tenants to relapse and thus remain in treatment…and in the three-quarter home. This vicious cycle is perfectly encapsulated in the articles headline “A Choice for Recovering Addicts: Relapse of Homelessness.” Read the full article for more details.

However, the article neglects the opportunity to elucidate the root cause of the existence of these three-quarter homes: lack of a sufficient, standardized and coordinated health care system for the treatment of addiction and other mental diseases. A critical problem in the American healthcare system is the lack of adequate inpatient medical treatment for people suffering from addiction, and is why people get referred to the three-quarter homes in the first place.

Addiction is a complex mental health disorder that requires an individual treatment plan that may involve medication, counseling, group and/or individual therapy, and other options. Without a well-funded, evidence-based, medical treatment program formulated for an individual’s addiction, they are likely to fall into the purgatory of three-quarter homes or even worse, the streets or prison. Ultimately homes likes these are allowed to exist due to the lack of adequate treatment options and facilities for addicts.

 And of course, the medical and treatment culture of addiction cannot be changed until the stigma against addicts and addiction is changed. Addiction is a medical disease and needs to be treated as such.

 

Huff Post Piece on Treatment of Opioid Addiction

A very well written article. Emphasizes that addiction is a medical disease that requires evidence-based (scientifically researched and proven) treatments. In fact, the piece includes quotes from the head of my lab, Dr. Mary Jeanne Kreek of the Rockefeller University.

http://projects.huffingtonpost.com/dying-to-be-free-heroin-treatment