Opioid prescription overdose and abuse – Staying safe while reducing pain

A new article just published in JAMA (see here) reports a strong relationship between high-dose opiate prescribing and accidental overdose deaths. The authors focused on a sample of Veterans and found that those prescribed more than 50mg of morphine per day, or the equivalent of other opiate drugs, we much more likely to die of such overdose than patients being prescribed lower doses. Fortunately, only about 20% of the patient-months (a measure of how many people were prescribed a specific dose for how long) were prescribed these high doses but the rate of overdose for this group was 3 to 20 times higher! Continue reading “Opioid prescription overdose and abuse – Staying safe while reducing pain”

A new candidate for ADHD medication: Amantadine and the rise of non-stimulants

It is well known that ADHD diagnoses and substance abuse problems are closely associated. It is estimated that substance abuse problems including dependence are up to twice as common among individuals with ADHD, which is not surprising given the impulsivity factor involved in ADHD. The problem is that until recently, most medications for ADHD have belonged to the stimulant category and as many, including us, have written before it is probably not the best idea ever to give drugs that have a relatively large abuse probability to people who are relatively likely to develop substance abuse problems. Right?

We’ve already written about atomoxetine and bupropion, two drugs with relatively low abuse potential (since patients don’t actually feel “high” from them) that are being successfully used in treating ADHD. But there is little doubt that the type of effect seen among patients who are using stimulants (like adderall, ritalin, etc.) isn’t being observed among patients taking non-stimulant medications. All of this means that patients on non-stimulants are getting less bang but with less risk. A dopamine agonist by the name of amantadine might change all of that according to a recent study.

Amantadine versus stimulants for ADHD treatment

Fourty children between the ages of 6 and 14 were enrolled in the study conducted in a psychiatric hospital in Iran. The kids were randomized into two groups a methylphenidate (ritalin) and amantadine group. Over a six week period the kids were assessed four times – at intake and then every two weeks -using an instrument that parents and teachers (who didn’t know what medication the kids were getting) would use to rate the child’s behavior on the 18 ADHD symptoms listed in the DSM-IV.

Amantadine may soon offer a new non-stimulant medication option for ADHD treatmentThe final findings were very encouraging (see picture): The kids in both conditions improved greatly over the 6 weeks of the study and no difference was found between the two medications. the children in the amantadine condition actually suffered less side effects and significantly so when looking at side effects common to stimulant medication such as decrease in appetite and restlessness. While more studies are obviously needed, this randomized trial shows that amantadine is not only safe, but it may be safer than at least some stimulant medications while also providing the same effect on ADHD symptoms. Given that approximately 30% of patients don’t respond well to stimulants and that some families are afraid of giving stimulant medications to their children, at least partially because of the risk of substance abuse issues, non-stimulant medications can be an attractive alternative, and it seems like amantadine can deliver.

Final thoughts from Dr. Jaffe on ADHD medications and amantadine

One of the main reservations I have about the notion of using this medication for ADHD is that NMDA receptors are very important in learning, so it may be that we’re helping to resolve attention problems but making it more difficult to actually create memories that are crucial for learning. More research is necessary to see if these decreases in impulsivity are accompannied by improvements, and not reductions, in learning ability.

So, if you’re considering medicating a child who has been diagnosed with ADHD, I strongly support the notion given the difference that medication has made in my own life. However, I urge you to be educated and to consider non-stimulant options, especially as more are researched and as that treatment option becomes more available, less costly, and less likely to lead to abuse of the drug. With prescription drug abuse one of the fastest growing problems in the U.S., being careful is just sound advice.

Citation:

Mohammad-Reza Mohammadi, Mohammad-Reza Kazemi, Ebtehal Zia, Shams-Ali Rezazadeh, Mina Tabrizi, Shahin Akhondzadeh (2010) Amantadine versus methylphenidate in children and adolescents with attention deficit/hyperactivity disorder: a randomized, double-blind trial. Human Psychopharmacology.

Some parkinson work showing effect of amantadine: http://www.springerlink.com/content/76r5wxux8wn52rq5/fulltext.pdf

The Myth Of “Loss of Control” As A Scientific Truth Of Addiction

All About Addiction aims to be a place where an open conversation about issues relevant to addiction can be discussed. To that end, the following is a piece from Christopher Russell that challenges the notion that people in some way lose control over their behavior suggesting instead that their seemingly compulsive behavior is actually volitional. Look for an upcoming post featuring Dr. Jaffe’s views on some of the points made by Christopher.

The Myth of “Loss of Control” – By Christopher Russell

Popular wisdom among addiction neuroscientists states that while initial drug use is voluntary, with repeated drug consumption the consumer moves closer to a critical, tipping point separating non-addicted from addicted drug use (e.g. Leshner, 1997). At the passing of this critical point, believed to reside in drug-induced changes to one or more brain sites and gene expression, the individual is argued to lose his ability to control his use of drugs thereafter. Beyond this point, drug use is now something which happens to the individual, compelled by pharmacological causes, not something the individual does for phenomenological reasons.

This notion of a physical “loss of control” as an explanation for why some people continue to use drugs has prevailed as the core hypothesis of the view of addiction as a progressive disease for the past 200 years (Levine, 1978) and today remains largely accepted by the general public as a taken-for-granted, scientifically-proven truth of addiction. Furthermore, the primary use of the word addiction has come to describe a particular set of behaviours which have a causal basis operating irrespective of the will of the individual (Davies, 1996), with “addicts” used as the term to distinguish those who are no longer able to control their drug use from those who are still able to control their drug use.

But why has this belief become so ubiquitous among the general public when the neuroscience community has produced no evidence which is sufficient to warrant the conclusion that certain individuals are physically unable to stop using their drug? Additionally, no evidence has been provided which warrants the conclusion that a critical, tipping point exists in the brain at which a person shifts from non-addicted to addicted drug use, the point at which the “loss of control” is assumed to occur. Both beliefs remain hypotheses for which there is as yet no evidence, however, the public  understanding tends to be that these arguments have been long since proven as basic truths of addiction. What we do know and can show today is that some people find quitting a drug to be easy, a bit hard, quite hard, or extremely difficult. But evidence of the difficulty to exercise control should not be confused with an inability to exercise control, no matter how much the evaluation “I can’t stop” feels like a literal truth about our capabilities. This 3-part blog describes what we can and cannot show about the nature of drug use today and why the “loss of control” myth has prevailed as a “fact” of addiction for many people.

What we can and cannot show about addiction today

What we can and cannot show about the nature of addiction today is summed up by Akers (1991), a sociologist:

“The problem is that there is no independent way to confirm that the “addict” cannot help himself and therefore the label is often used as a tautological explanation of the addiction. The habit is called an addiction because it is not under control but there is no way to distinguish a habit that is uncontrollable from one which is simply not controlled”.

In other words, we have only shown that some people do not stop using drugs, not that they cannot stop using drugs. The belief that some people cannot control their drug use will soon be shown to be a scientific fact, which comes from the moral judgment that people who do not stop when they say they really want to stop and who continue to use even to the detriment of other important things in life like work and relationships must be doing so not of their own will, but rather, their behaviour must be being compelled by a force outside of their will. In other words, the value-laden judgment is that no person in their right mind would voluntarily pursue this life; therefore, it fits with our view of a moral society to think that a drug “addict” is not a morally reprehensible person, but rather, must be using drugs against his will. But we must remember that to say “for why else would this poor person continue to use drugs?” is a value-laden statement about how we believe morally decent humans should behave. We should not infer that people cannot stop using drugs simply because we observe them not stopping. This may be useful information in itself, but is not evidence of a loss of control.

What medications do and do not do

Of course I do not deny that the use of medications like naltrexone, acamprosate and buprenorphine make it easier to forego certain drug use by blocking parts of the brain which motivate drug use. I would encourage people to use these medications if they find it helps them to not use other drugs. However, reducing the difficulty of quitting should not be confused with restoring the individual’s ability to quit as if this ability was at any point lost. Medications can help people quit using drugs and great strides are being made to manufacture medications which make the process of quitting easier to do and tolerate. However, these medications are not necessary for controlling drug use in the way heart medicines, radiation therapy, and insulin is necessary to stave off the mortal threats of heart conditions, cancers, and diabetes respectively.  These groups of people do not have agency over their conditions in the way drug users have over their behaviour.

No medication has yet been shown to restore a drug user’s free will to reject drugs. Additionally, manufacturing medications has long been considered by addiction researchers such as Bruce Alexander, Stanton Peele, and John Davies to be focusing on the thin edge of the wedge; too much focus on the uses of medication, they would argue, restricts the need for drug users and treatment providers to consider a broad social analysis of why drug use is so prevalent in our societies.

The paradox of “behaving responsibly” after control is lost

The paradox inherent to the belief that some drugs erode free will and others can restore free will is that a drug user is expected to exercise his control and his will to sign up for and attend treatment and take medication like a “responsible” person should do precisely when we believe he has been robbed of his control and will to make choices about drugs. This paradox is also seen in the myth that an “addict can only quit after he hits rock bottom” which is promulgated by the 12-step movement; we expect people to show free will to quit precisely when they are thought to be least free to make choices about drugs. In other words, we expect so much self-control from those we believe are no longer capable of self-control!

The defence of this paradox has tended to be along the line of “he has not lost his free will to control all parts of his life, only the parts which involve drugs”. In one of his early speeches in San Diego, June 6th, 1989, William Bennett, former National Drug Policy Director and drugs czar appointed by President George H. W. Bush, defined an “addict as a man or a woman whose power to exercise rational volition has been seriously eroded by drugs, and whose life is organised largely – even exclusively – around the pursuit and satisfaction of his addiction”. Bennett’s statement reflects a common logical contradiction. Organisation of one’s life around anything is a rational skill, a wilful act, often requiring complex cognitive operations to be performed such as planning for an event which is two and three moves ahead. As Schaler (1991: 237) notes, “If an addict’s power to exercise rational volition is seriously eroded, on what basis does the addict organise life?” Interestingly another curious medical-moral contradiction by Bennett was noted by Massing in his book The Fix. Massing said “Addicts were in his (Bennett’s) view irresponsible individuals lacking basic levels of self-control” (p195). If these people do lack the capacity for self-control, how can they be responsible for not showing self-control? If they were irresponsible, it is their irresponsibility which causes drug taking; self-control is irrelevant. Bennett appears to be of the view that addiction is a moral failing which the addict is helpless to prevent, which is logically impossible.

Instead, what we do observe is that drug users are actually very good at putting in place the conditions by which drugs can be obtained, and that many people who are diagnosed as drug addicts do show a great capacity for self-control of behaviours except for those involving drugs. So addiction neuroscience is not pursuing a neurobiological basis of free will, per se, just the basis of our free will to control drug use, which is an even harder premise to swallow.

Stay tuned for Dr Jaffe’s reponse and part 2 coming soon.

References:

Akers, R. L. (1991). Addiction; the troublesome concept. The Journal of Drug Issues, 21(4). 777-793. (only available in print form at present).

Davies, J. B. (1996). Reasons and causes: Understanding substance users’ explanations for their behaviour. Human Psychopharmacology, 11, 39-48.

Leshner, A. I. (1997). Addiction is a brain disease, and it matters. Science, 278,45−47.

Levine, H. (1978). The discovery of addiction: Changing conceptions of habitual drunkenness in America. Journal of Studies on Alcohol, 39, 143−174.

Massing, M. (1998). The Fix. University of California Press Ltd; London England.

Schaler, J. A. (1991). Drugs and free will. Society, 28(6), 235-248.

Adding environmental factors to pharmacogenomics improves treatment outcome

Hopefully you’ve read our previous discussion of pharmacogenomics but in case you haven’t (and you should), it is the science of personalized medicine (medications and medication-dosing) based on an individual’s genetic code. Well, nothing ever stays simple with genetics and although by now it is pretty clear that aside from considering what is knows as functional variation in genetic code (what everyone was talking about during that whole human genome project thing – changes in human genetic code that directly affect protein function) we also need to consider epigenetics – or that part of the genetic code that we used to think meant nothing (right, that was going to work out) and we now know influences that expression of all those other genes we care about.

Pharmacogenomics – Personalized medicine in treatment for heart disease

Well, it seems that some real advances are being made in the area of heart medication in terms of pharmacogenomics. From aspirin dosing to issues concerning medications that help with clotting after open-heart surgery, the medical field has been working hard on figuring out what drugs and what doses people who vary on specific genes should be prescribed. The article  by Baye and Wikle that drew my attention back to this topic brings up an important consideration that I believe will play a significant role in making sure that medications for substance abuse benefit equally from pharmacogenomics – what they call biogeographical ancestry. Biogeographical ancestry is the politically correct way of asking where on earth people are from, and given the relatively (a few hundred years) recent mixing of African descendants with people from Central and South America, Caucasians with Africans, and a whole other slew of mixes, knowing ones geographical ancestry adds a whole lot of knowledge to our genetic equation because the genetic code hasn’t had the time to mix together fully and so it still clumps together in ways that make analyzing its variability much easier.

Pharmacogenomics and addiction treatment?

What the heck does this have to do with drug abuse you ask? Well even aside from a strong recent push by NIDA director Dr. Nora Volkow, it is becoming clearer and clearer, at least to me, that medication are going to play a bigger and bigger role in treating addictions. Drugs like Vivitrol, Suboxone, and Zyban are making a real difference in the success rates of those seeking help from addictions and I think that as we get better and better at tailoring the drug selection and doses, those medications, and other that haven’t even been discovered yet, will help us get over the initial hump in treatment – the danger zone.

You see, most people who abuse drugs are not what we call addicts. They’re using more than they should and likely need a nudge from their doctor or some real reason, like a likely oncoming heart attack, to tame their use or stop altogether. In fact, the vast majority of drug abusers stop on their own. However, there’s always that group of people who can’t stop on their own and even though right now we only get to treat them once they get in real trouble (cops, hospital, marriage, you name it), as we start incorporating screening for drug abuse into our medical system we will begin finding more of them at an earlier point in their drug troubled life. For them especially, but also for the chronic relapsers, these medication can make a world of difference and give them a chance at a life that may otherwise seem impossible – a life without drug abuse.Our experience with bupropion and quitting smoking proves that knowing a person’s genetic variability can really help determine their effective use of medications.

But for all the people these drugs help, there are always horror stories about individuals who’ve become addicts to the medication or for whom the meds themselves produced such horrible side-effects that staying addicted almost seems better. For them, I believe pharmacogenomics will make all the difference. And once we figure out who will and who won’t benefit from which drugs at what doses I think that the medical field in general, and substance abuse medication therapy in particular, will benefit greatly.

Citation:

Baye, T. M. & Wikle, R. A. (2010) Mapping genes that predict treatment outcome in admixed populations. Pharmacogenomics Journal, 10: 465-477

Here’s a link to an upcoming conference on pharmacogenomics for anyone interested in the topic:

Personalized Medicine: Principles to Practice
March 1, 2011
Dallas, TX, USA

This symposium brings together leaders in the field to address key aspects of the science of therapeutic individualization, the enabling technologies underpinning this biomedical revolution, and the evolution in policies that will advance personalized medicine principles into healthcare management tools for individuals and populations.

www.nature.com/natureconferences/prmd2011

Helping Addicts with medications for cravings

If we could make it so drug addicts could stop craving the substances that have brought them to their knees, would relapse rates drop and addiction-treatment success rates soar? I sure hope so!

Medications that stop cravings?

I’ve already written about a study by the renowned addiction researcher Barry Everitt showing that medications could be used in treatment to help addicts who are struggling with strong cravings and the effect of triggers (see it here). Still, in that study the researchers used a drug that blocked pretty much all memory formation and my original idea had to do with using a very common drug, one being used every day for hypertension, and more recently, in the treatment of PTSD.

Well, a study recently completed revealed that indeed, propranolol, a common beta-blocker, may be useful in greatly reducing the amount of time needed to overcome the sometimes crippling effect of triggers on behavior.

How this trigger to cravings study worked

The researchers trained rats to take cocaine, and after they were well trained, allowed them to press a lever for a light that had previously been associated with the drug. This is a common method to test the way animals react to triggers that have been associated with the drug. Even though the animals are no longer getting any cocaine when the light goes on, the fact that it had been previously associated with the drug makes the animals press the lever, like an addict triggered by something they’ve associated with their drug use.

The animals that were given propranolol immediately after every session took half as long to stop pressing for the drug-associated light. It took multiple administrations of propranolol (seven to be exact), but the effect was clear. The next step is to see if the same effect can be observed in people.

Helping addicts transition to outpatient substance abuse treatment

I’ve been claiming for the past few years that if we look in the right places, we can find many ways to help struggling addicts who are having a hard time quitting using currently available methods. I think that the notion that sticking to the “best method we have right now” is unwise given the fact that science has progressed quite a bit in the past 20-30 years. I agree, and am thankful, that the system works for some, but there’s no question that many still have trouble recovering from addictions that devastate their own lives and the lives of many close to them. I think these medications can offer some serious help.

The thing is, that if we could seriously reduce the impact of cravings on relapse rates, it’s possible that addicts would be ready to move from residential to outpatient substance abuse treatment  more quickly. Indeed, the main reason for keeping people in residential treatment is the thinking that they’re not ready to be in the world given the influence of triggers. My guess is that this is true for some addicts, but if we could provide an intervention, like propranolol, that would significantly reduce the influence of triggers, outpatient substance abuse treatment, which is a cheaper option, will be useful for many more. This would mean more people in treatment that truly works for them for less money. Sounds good to me.

Citation:

Ashley N. Fricks-Gleason & John F. Marshall (2008). Post-retrieval ß-adrenergic receptor blockade: Effects on extinction and reconsolidation of cocaine-cue memories. Memory & Learning, 15, 643-648

Depression medication – Evidence and usefulness

Depression medication has been widely prescribed since the early days of Prozac (Fluoxetine) and the discovery that depression can be helped by taking a pill. A new study shows that in reality, only those who suffer from severe depression may actually benefit from taking the meds though.

Depression is commonly seen in addiction treatment so I think the topic is relevant for us. But before I explain the details, a little review of depression medication would be useful.

A review of depression medication

The type of medication has gone through some major changes, starting with TCAs and MAOIs and ending up at SSRIs and SNRIs. MAOIs blocked an enzyme from breaking down Serotonin, which increased the levels of this emotion-enhancing neurotransmitter (MDMA, or ecstasy effects Serotonin as well). SSRIs and SNRIs block the recycling of serotonin (SSRI means Selective Serotonin Reuptake Inhibitor) and a broader group of neurotransmitters (SNRI = Serotonin Norepinephrine Reuptake Inhibitor).

The problem with MAOIs was that their side effects were often worse than the depression the patients were suffering. The same side effect problems were also common with TCAs (tricyclic antidepressants) because of the numerous effects they had on many systems in the brain.

MAOIs and TCAs are essentially gone from the U.S. market but are still prescribed in other countries to some extent. SSRIs and NSRIs are the most common drugs for depression treatment here, but there are still major differences between different specific pills.

New study results – Pills good for severe depression

This new meta-analysis (a combined analysis of a bunch of older papers), seems to show that Tofranil (a TCA) and Paxil (a SSRI) are only more effective than a placebo sugar-pill in patients who suffer from severe depression. The problem is that most people who are prescribed anti-depressants today suffer from mild or moderate depression. This brings into question the wide use of the drugs.

It even seems possible that the reason side effects are worse than the depression for some patients is because the depression itself was simply not that severe in the first place and would have been better helped by the use of psychotherapy without medications.

Some limitations of the study

It’s important to realize that this study looked only at two different medications, both of which are known to have a significant problem with negative side-effects. Future studies will most likely cover more of what’s available and since depression and addiction are so closely associated, you can count on me revisiting this again!

Citation:

Jay C. Fournier; Robert J. DeRubeis; Steven D. Hollon; Sona Dimidjian; Jay D. Amsterdam; Richard C. Shelton; Jan Fawcett (2010). Antidepressant Drug Effects and Depression Severity: A Patient-Level Meta-analysis. JAMA, 303(1):47-53.

Steven Tyler deals with pain killer addiction by checking into rehab

After the recent death of Michael Jackson, and possibly Brittany Murphy, due to prescription drug overdoses, Steven Tyler, the lead singer of the mega-band Aerosmith, has checked himself into rehab for pain-killer addiction.

Many pain killers commonly used are opiates (which are very similar to heroin), and many chronic-pain sufferers resolve to taking such drugs in high quantities and for many years. Such use can easily lead to dependence and serious withdrawal symptoms.

We wish Tyler all the best in his rehabilitation efforts. Stay strong Steven!