"What If It's Just a Placebo?"

I just received an email from a man who has been diagnosed with ADHD and is afraid to try stimulants because of some of the bad press and unfavorable articles he has read. He wants to try the medication Amantadine (Symmetril). Amantadine is being used successfully by a clinician named William Singer at Harvard Medical School for his ADHD patients. His positive results in 400 patients, (all children) were reported in Hallowell’s book Delivered from Distraction as a potential treatment for ADHD.

Amantadine has been around for many years, first as a treatment for Parkinson’s Disease and then as a treatment for Parkinson-like side effects to the old antipsychotic medications. More recently it has also been used to treat early flu symptoms. The latest pharmacology text says it has enhancement effect on dopamine, but it is not known exactly how it works.  In contrast, lots of scientific data and studies explain how stimulants work, a reassuring fact when using them.

I certainly don’t question that Dr. Singer is getting good results with Amantadine in ADHD patients, but could his positive results be linked to factors other than the Amantadine itself? What if a randomized placebo controlled study compared active Amantadine to an inactive placebo and found that the placebo group did about as well as the Amantadine group?  In other words, they both showed improvement.  What would that mean?  It would mean that all the things that go into a patient’s involvement with treatment including the decision to get help, monitoring of symptoms, interaction with the entire office staff, etc., would be contributing to the patient’s improvement, but that the Amantadine itself was not contributing much if any.  Possibly, Amantadine could even make ADHD worse.

One of my favorite examples of this phenomenon was an open study showing that progesterone helped PMS.  An open study, in comparission to a contolled study, records the patients response to treatment, but does not compare their response on an inactive form of the medication.  Later, a placebo controlled study was conducted and patients taking placebo reported better response than those taking progesterone.  This meant that progesterone actually made PMS worse in these patients, but not enough to neutralize the placebo benefit inherent in any treatment.

What am I saying by all this?  Amantadine may be a beneficial treatment for ADHD.  I hope it is.  But I have been burned many times in the past by the promise of treatments that under rigorous study "didn’t pan out."  What if you try it and it seems to work great?  How do you know it’s not a placebo response?  You don’t, but if you’re doing great and you think it’s helping, what difference does it make?

Read Dr. Jones’ response to the email on Amantadine.