The Corpus Callosum

Stimulant Improves Sleep

Medscape has one of their brief 0.25 CME articles on the subject of
methylphenidate (Ritalin, et. al.) and the effect
it has on sleep.  (You have to register to read it, but
registration is free.)

This is interesting because it illustrates nicely how
psychopharmacology can be confusing.  In this post, I try to
show some of the ways in which this confusion can occur.

href="http://www.medscape.com/viewarticle/571987">Stimulant
Improves Sleep in Adults With ADHD

News Author: Pauline Anderson
CME Author: Charles Vega, MD

March 26, 2008 — A study suggests that the central nervous
system stimulant methylphenidate improves sleep patterns in adults with
attention-deficit/hyperactivity disorder (ADHD).

Researchers found that the stimulant had a positive effect not only on
polysomnographic recordings of sleep, reducing parameters such as sleep
latency (the period between going to bed and going to sleep) and the
number of nocturnal awakenings, but also on subjective sleep quality,
said the study’s lead author, Esther Sobanski, MD, head of the
scientific working group on adult ADHD, Central Institute of Mental
Health in Mannheim, Germany…

This is counterintuitive.  One would not expect a stimulant to
improve sleep.  


Of course, you might, if you say to yourself that 1) Stimulants do the
opposite of what you would expect, if the person has ADHD.  2)
What I would expect in a non-ADHD person is that the stimulant would
cause insomnia, 3) Therefore, it makes sense that it would improve
sleep in someone with ADHD, since that is the opposite of what I
otherwise would expect.

That kind of reasoning is attractive to people, but it is not very
reliable.  Even someone with ADHD can get insomnia from
methylphenidate, depending of the dose, the timing, and individual
factors.

It is very easy to assume that a particular drug will have a particular
effect.  Those assumptions tend to be based upon the logically
nettlesome process of thinking of the drug as a member of a class of
drugs, then drawing inferences based upon what you know, or think you
know, about that class of drugs.  

This is particularly tricky if what you know about a class of drug is
based entirely upon your experience with a member of that class.

There are many ways that this kind of inferential reasoning can go
astray.

One way that this kind of error occurs is due to the haphazard way that
drugs are classified.  Some classes are defined by chemical
structure.  For example, the tricyclic antidepressants are
placed in that class because they have three carbon rings.
 But it turns out that the occurrence of the three rings is
not particularly important.  

To illustrate: imipramine is a tricyclic antidepressant.  It
has effects roughly comparable to those of venlafaxine.  (I
know some people might want to quibble about this, but please don’t
bother.)  It turns out that carbamazepine also has three
rings.  It looks a lot like imipramine.  But the
effects are very different: carbmazepine is an anticonvulsant.
 The point is, that the effect of imipramine is a lot more
like that of venlafaxine, than carbamazepine, even though the chemical
structure is more similar to carbamazepine.  So that is one
way that classification of drugs can be confusing, leading to erroneous
inferences.  

Another:  imipramine and bupropion both are classified and
antidepressants.  They both treat depression, but in different
ways.  Their chemical structures are not similar.
 Their mechanisms of action are not similar.  Their
clinical efficacies are similar, with respect to depression.
 But when it comes to anxiety, they are very different. They
both work for depression, but only imipramine has an appreciable effect
on panic disorder.

Or take (figuratively) imipramine and clomipramine.  Both are
antidepressants.  Both are tricyclics.  In fact, the
only difference, chemically, is a single chlorine atom tacked to the
side of clomipramine.  Both are effective for panic disorder,
and effective for generalized anxiety disorder.  Panic and GAD
are both anxiety disorders.  Obsessive-compulsive disorder is
an anxiety disorder, too.  So it would be tempting to think
that both would work for OCD.  But clomipramine has a great
effect in the treatment of OCD, whereas imipramine has none.

So it is clear that faulty inferences about medication can come from
the dorky way that we put medication into various classes.
 The point about OCD also illustrates that the classification
of illnesses can lead to similar confusion.  

What are some of the other ways that inferences about medication can be
faulty?

One common way is for people to assume that a given drug will effect
everyone the same way.  That is false.  Drugs have
very different effects are different people.  Sometimes this
is due to the presence of absence of disease.  An antibiotic
might have a big effect on someone with pneumonia, but no effect of
someone who has no infection.

Another reason for the same drug to have different effects on different
people, is that everyone is different.  Some people will
metabolize certain drugs differently, leading to dramatic differences
in effect.  That is the reason that alcohol effects Europeans
so differently
than Native Americans.  

The dose matters, a lot.  The effect of a higher dose is not
necessarily a mere amplification of a lower dose.  It could be
the opposite.  

Another source of faulty inferences occurs when people construct an
erroneous spectrum, or continuum, as a kind of mental model to
understand, or misunderstand, medication effects.  A common
one is to think of medication as falling on a spectrum, from uppers to
downers.  I’ll see something like this, sometimes: 1) All
psychiatric medication is either an upper or a downer.  2)
Amphetamines are uppers, barbiturates are downers.  3)
 Downers make people depressed.  4)
 Antidepressants make people undepressed.  5)
 Therefore, antidepressants are uppers.  6)
Therefore, antidepressants share properties with amphetamines…

Before the 1950′s pretty much everything in psychiatry was an upper or
a downer.  But that hasn’t been true for over 50 years.
 I don’t see that particular fallacious line of reasoning very
much anymore, but I saw it a lot in the 1980′s.  

This is all a long-winded way of saying that experience always trumps
intuition, when it comes to psychopharmacology.  That is not
to say that intuition is useless, just that it is dangerous.

Comments

  1. #1 AnnaZ
    April 4, 2008

    The upper or downer line of fallacious reasoning is still repeated in entertainment and popular media, where it’s pretty common to see anti-depressants treated as a happy pill that gets you high. Sadly, this misrepresentation is sometimes picked up on by those teens willing to experiment with the family medicine cabinet.

  2. #2 Noni Mausa
    April 4, 2008

    In a Ngaio Marsh mystery from the late 20s, a woman is suspected of having done the murder. But it was proven that she had taken her medication and gone to bed — thus, could not have gotten up and done the deed.

    Her medication was aspirin.

    Pain killer = sedative
    Aspirin = pain killer
    ergo Aspirin = sedative

    Then of course you have the three different effects of codeine on three species — in humans, it sedates, in dogs it causes miserable nausea, and in cats it causes frenzy.

    I’m an not yet diagnosed woman struggling with ADHD. For years I would want to stay awake and alert for an event or homework, so I would try to have a big cup of coffee. It never perked my up or made me alert, although it could prevent me from actually sleeping. Till I did some reading on ADHD, I had no idea why the wonderful stimulant caffeine worked for everyone else but not for me.

    Noni

  3. #3 Hyperion
    April 5, 2008

    I’ve (ADHD individual) been taking Adderall XR at night as a sleep aid for several years. It’s the only thing that reliably helps me go to bed. It’s not just a matter of sedative vs. stimulant (although the sedating effects do play a role), but in my experience it’s also that these medications help block out distractions and slow down the racing, daydreaming, ADHD mind.

    Also, the neurological impulses that tell your body and mind to “sit down and shut up” are probably similar to the ones that tell your body and mind to “lay down and go to sleep.”

    One odd note…I used to take Adderall XR 3 times a day on 8 hour intervals (it only lasts 8 hours for me). Oddly enough, I would sometimes find myself “shifted” and sleep during one of the daytime dose intervals, and my body would then register that as the “night/sleep” shift with regards to circadian rhythms, and adjust accordingly.

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