The Corpus Callosum

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.

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.