6/14/2000 – Paxil Causes Brain Atropy

Thanks to Ian Goddard for forwarding us this information on Paxil and brain

Paxil Causes Brain Atropy

This is a major finding: the thalamus in children
taking Paxil was observed to shrink after 12 weeks.
This is portrayed as a good thing, since the study
claims that the thalamus of OCD patients is too
large and 12 weeks of treatment shrunk the brain
region to normal size. Even if such atrophy after
12 weeks is beneficial (a big “if”!!), what happens
after 50, 100, 200 or more weeks of brain atrophy?

Here’s the abstract. Following that is a remarkable
reply I got from one of the authors of the study.

Arch Gen Psychiatry 2000 May;57(5):449-56

Decrease in thalamic volumes of pediatric patients with
obsessive-compulsive disorder who are taking paroxetine.

Gilbert AR, Moore GJ, Keshavan MS, Paulson LA,
Narula V, Mac Master FP, Stewart CM, Rosenberg DR

Department of Psychiatry, Wayne State University School
of Medicine, Detroit, Mich, USA.

BACKGROUND: Thalamic dysfunction has been implicated
in obsessive-compulsive disorder (OCD). While OCD
frequently has its onset during childhood, to our
knowledge, no prior study has measured neuroanatomical
changes in the thalamus of patients with OCD near the
onset of illness, and before and after treatment.
METHODS: Volumetric magnetic resonance imaging studies
were conducted in 21 psychotropic drug-naive children,
aged 8 to 17 years, with OCD and 21 case-matched healthy
comparison subjects. Magnetic resonance imaging studies
were also conducted in 10 of the 21 patients with OCD
after 12 weeks of monotherapy with the selective
serotonin reuptake inhibitor, paroxetine hydrochloride.
RESULTS: Thalamic volumes were significantly greater
in treatment-naive patients with OCD than in controls
but declined significantly after paroxetine monotherapy
to levels comparable with those of controls. Decrease
in thalamic volume in patients with OCD was associated
with reduction in OCD symptom severity. CONCLUSIONS:
Our findings provide new evidence of thalamic
abnormalities in pediatric OCD and further suggest
that paroxetine treatment may be paralleled by a
reduction in thalamic volume. These reductions may,
however, not be specific to paroxetine treatment and
could be due to a more general treatment response,
and/or spontaneous improvement in symptoms. Our
findings are preliminary given the small sample size
and our inability to measure discrete thalamic nuclei.


From Dr. David Rosenberg, an author of above study:

At 05:07 PM 5/8/00 -0400, you wrote:
>Hello Doctor Rosenberg,
>I just read your study in the May issue if the Archives
>of Clinical Psychiatry. I think it could prove to be a
>real breakthrough. The question I have is what’s the
>cause of the observed reduction of thalamus volume?
>Could it be a result of cell death or the loss of
>cell mass? If not that, than what other cause?
>Thank you for your time and attention.
>– Ian Goddard

At this point it’s not clear although we have several hypotheses. We saw a
differential maturation of thalamic volume in OCD patients and controls that
might reflect a neural network dysplasia with a possible reduction in
synaptic pruning in OCD pts vs controls (the normal pruning of neural
elements during peripubertal period). Cell death or loss of cell mass is
one possibility, probably best looked at in post-mortem studies. We recently
published a priority communication in biological psychiatry (february 2000)
showing decreased NAA/Cho +Cr levels suggestive of possible neuronal
dysfunction (NAA is thought to be a marker of neuronal viability); however,
more recent analysis also suggests potential choline abnormalities. Finally,
the thalamus is a densely serotonergic region and possible aberrations in
development could lead to altered volume. This was a surprising finding,
clearly requires replication with larger samples; also, our inability to
measure subdivisions of the thalamus: we are working on a new program that
allows us to do this and we hope to delineate whether medial regions (which
we would hypothesize) would be more affected)

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