December 6, 2004

Why Have the Tricyclic and SSRI Antidepressants Both Failed to Help Children?

Higher rates of suicidality for children taking the SSRI antidepressants were finally confirmed by an army of statisticians and scientists at yesterday's FDA meetings on the Prozac type drugs.  One can expect approximately two to three children out of a hundred taking the drug to experience thoughts or take actions related to suicide.  This is over and above any suicidal type behavior associated with the depression that is being treated with the drugs...

A panel advising the FDA on the SSRIs and kids, voted 15-8 to recommend a black box warning for the SSRIs on the official labels of these drugs.  During the discussion periods, it was clear the panel was toying with the idea of recommending an outright ban on the medications for children's depression as was done by the British equivalent of the FDA in the United Kingdom.  Still there was hesitancy because of impassioned pleas primarily from organized psychiatry that the drugs are helpful in children's depression.

The psychiatrists' impressions, however, were not confirmed by the data.  Only three of fifteen studies showed positive results for the SSRIs compared to a placebo or sugar pill.  As part of the controversy, eight of the negative studies were withheld from doctors' and the public which has led to Congressional investigations and likely new regulations from the FDA.

Lost in all the concerns over increased suicidality and concealment is an important fact.  This is the second time in thirty years a class of anti-depressants which were demonstrated to be effective in adults don't work in kids.  A dozen or so studies of the tricyclic antidepressants (Elavil, Imipramine, etc.), the anti-depressants used in America before Prozac became available, also failed to demonstrate effectiveness in children during the 1970s.

Why is there a difference in how adults and children respond to these drugs?  Despite a lot of scientific propaganda (and TV commercials) we really don't have a good idea exactly how these medications work.  Yes, neurotransmitters that we've identified like serotonin, dopamine or norepinephrine may be involved but exact mechanisms of action remain obscure.

Still how different really, could the brain of a fifteen year old be compared to a twenty-five year old.  There isn't much difference in their respective metabolism rates of the drugs.  The distinction between adults and children in these studies is usually made at the year eighteen.  One must look beyond the environment of the synapse and consider difference between the environments of children and adults to get a clearer picture.

Children are far more emotionally vulnerable and dependent on their environments due to their physical size and emotional and intellectual immaturity.  We know from PET and MRI scans that experiential factors such as stress or psychotherapy affect neurochemistry as much as psychiatric drugs.  Could it be that the SSRIs can only affect children's neurochemistry and ultimate behavior so much compared to effects of family, school, peers and neighborhood?  People over eighteen have far more choices over how or where they live.  They have far more control over their own experience than children.  Perhaps, SSRIs can make a greater difference in outcome when a person has more control and less dependency over their environments.

It's ironic that in the debate on the effectiveness and safety of the SSRIs in children that almost no one at the conferences mentioned the children's environments and non-drug interventions.  Cognitive behavioral therapy was discussed in one study, but discussion on interventions with family, school or public health issues involving neighborhoods were absent.  It seems almost that with a corporate profit making interest promoting one intervention, drugs, other potential important actions for children like family therapy or special education get lost.  The failure of the SSRIs and tricylics to help children's depression should remind us that there's a much greater world out there in which children need help than just their brains.

2099 Mt. Diablo Blvd., Suite 208
Walnut Creek, CA 94596