Saturday, November 7, 2015

The Myth of "Rescue" Medications

First off a clarification.  I am talking about the specific case where a short acting medication is added to a long acting form of the same medication and not "as needed" medication in order to determine the correct daily dosage.   In my line of work it occurs in two situations, long acting stimulants and their immediate release versions and long acting opioids and their immediate release versions.  I will illustrate that these practices are driven by myths about the medication rather than pharmacokinetics.  There is always the additional consideration about addiction lurking in the background, but the conscious and unconscious determinants of addiction frequently depend on the myths that I will be discussing about medication effects.



The example that I will use here is Concerta (long acting methylphenidate) compared with immediate release methylphenidate.  The graph from the package insert above shows the plasma concentration from a single 18 mg dose of Concerta and three successive 5 mg doses of immediate release methylphenidate.  As noted in the comparison of the curves and additional pharmacokinetic parameters the curve associated with three successive doses of immediate release methylphenidate is nearly identically replicated by a single dose of Concerta.

What is happening when additional doses of a immediate release methylphenidate are prescribed to a person who is already taking Concerta?  I  have seen this happen with sustained release stimulants and sustained release opioids.  I have seen it happen as a single dose of the immediate release preparation or multiple doses over the course of the day.  The patient is usually advised that this is a "rescue" medication that they should take if needed.  The first possibility is that the dose of sustained release medication has not been optimized and a higher dose of the sustained release medication needs to be given.  That is usually not the case.  The most frequent reason for taking the rescue medication is that the patient believes they are experiencing breakthrough symptoms and for a moment they need a higher dose of a medication.  There are serious problems with that concept.  As can be seen from the curves comparing Concerta and methylphenidate it does not make pharmacokinetic sense.  Any additional dose of immediate release methylphenidate on top of Concerta would greatly increase the expected plasma concentration at that point.

The main problem is that both ADHD and non-cancer pain are chronic conditions.  By definition they do not respond well to medications and they will not resolve typically with any amount of the medication.  Many people who take stimulants for ADHD assume that the human brain can be fine tuned with a medication.  There is also a widespread myth that they are cognitive performance enhancing drugs.  The real effects of stimulants are modest at best and there is no good research evidence to support a cognitive enhancing effect.  A similar bias exists for the use of opioids for chronic non-cancer pain.  The person believes that "If I take enough of this medication - my pain will be gone."  Study after study of opioids for chronic non-cancer pain shows that pain relief with opioids is modest at best, with results very similar to what would be expected with non-opioid medications like gabapentin and antidepressants.

There are secondary problems with believing a medication will produce perfect cognition or perfect pain relief.  The first is a tendency to see any medication with such powerful abilities as being able to solve a number of problems that are not the primary indication for the medication.  As an example, with a stimulant - if this medication has such a profound effect on my cognition maybe it can help with with other difficult problems like excessive appetite and weight problems or feeling like I don't have enough energy at certain times during the day.  With the opioid the  thought typically is that it can be used for mental pain as well as physical pain and it is used to treat anxiety, depression, and insomnia.  Whenever a medication is not used strictly for the prescribed indication there is a risk that it will be used for "what ails you."  The danger is dose escalation and addiction.  There is also the risk of attributing too much of an effect to the medication when it does not appear to be doing much.  A person may start to believe that they can't function without the medication but a detailed review of their target symptoms and ability to function shows that there has been a negligible effect.  And finally there is the danger of taking a medication that may produce euphoria, increased energy, and create a sense of well being and not realizing that at some point that is the only reason the medication is being taken.  I have had many people tell me that the medicine did nothing for their pain or cognition but that they kept getting refills because they "liked taking it."

There is what I call the Talisman effect, but probably to a lesser extent than with benzodiazepines.  Many people develop the idea that they are taking a medication that is much more effective than it really is and therefore they have to take it with them wherever they go.  They are conferring what are essentially magical properties to the medication and at some level thinking that they are unable to function in life without it.  They get anxious if they think about not having it or running out.  This not only causes a lot of unnecessary anxiety, but it also prevents the person from using other psychological or conditioning techniques that may work as well or much better than the medication.

These are some of the problems with the idea of taking a rescue medication if you are already on a long-acting form of the medicine.  Physicians in general do not do a good job of explaining these potential problems or even the basic problem of taking a medication that causes euphoria or reinforces its own use.  A more widespread recognition of these problems would go a long way toward curbing overprescription, overuse, and addiction to these medications.    

        
George Dawson, MD, DFAPA

References:

1.  Graph of plasma concentrations of Concerta and methylphenidate is from the package insert on FDA web site at:  http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021121s014lbl.pdf

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