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From: Linda Gore on 6 Feb 2006 21:03
Am J Psychiatry 163:159, January 2006
doi: 10.1176/appi.ajp.163.1.159
© 2006 American Psychiatric Association
This Article

http://ajp.psychiatryonline.org/cgi/content/full/163/1/159
Tourette's Symptoms Provoked by Lamotrigine in a Bipolar Patient
FLORIAN SEEMÜLLER, M.D., SANDRA DEHNING, M.D., HEINZ GRUNZE, M.D., and
NORBERT MÜLLER, M.D., Ph.D.

Munich, Germany
To the Editor: Lamotrigine is a modern anticonvulsant with established
antiepileptic and mood-stabilizing properties. We present the first
case, to our knowledge, of an adult bipolar patient who developed
multiple motor and vocal tics during treatment with lamotrigine.


Ms. A, a 55-year-old woman, was referred to our bipolar outpatient
center by her general practitioner for frequent recurrent depressive
episodes. Laboratory measures, including a CSF level, a magnetic
resonance imaging scan, and an EEG, revealed no hint of an organic
cause of her depressive symptoms. Because her history also revealed a
manic episode, she was diagnosed as having bipolar I disorder with a
rapid-cycling course. Lamotrigine monotherapy was initiated for mood
stabilization and was titrated up to 200 mg/day (a blood level of 4.6
µg/ml).
For 3 months, Ms. A's mood remained stable, but she began to develop
tics of increasing extent and complexity. She started to produce motor
tics, such as shrugging her right shoulder, wagging her hips, and
pawing her feet on the ground. Moreover, she was picking at her clothes
and blinking her eyes. In due course, she developed vocal tics for the
first time in her life. Thus, she then had repetitive throat clearing,
single expiratory grunts, and mental coprolalia.

At her follow-up visit, Ms. A reported a history of rare left shoulder
shrugging and head nodding for 2 years before referral to our clinic.
No previous vocal tics were reported. During childhood she suffered
from mild orofacial motor tics that disappeared spontaneously after 6
months at the age of 7. At that time, no diagnosis was made. Thus, Ms.
A had only two episodes of slight motor tics.

Suspecting an exacerbation of Tourette's syndrome due to lamotrigine,
we began to taper her lamotrigine dosage. With the reduction of
lamotrigine to 100 mg/day, most of her symptoms faded and disappeared
completely 2 weeks after total withdrawal.


Our literature search identified eight case reports describing the
induction of tics in children with epilepsy treated with lamotrigine
but none in adult nonepileptic patients (1, 2). In line with these case
reports, most of Ms. A's symptoms disappeared after dose reduction,
indicating a dose-dependent side effect. An explanation for the
exacerbation of Tourette's syndrome during lamotrigine treatment
remains speculative.

Inhibition of excitatory amino acid release can alter dopamine uptake
in the striatum (3). In addition, the potent inhibitory effect of
lamotrigine on the presynaptic release of excitatory amino acids might
also modify striatal dopamine uptake (4) and lead to the occurrence of
Tourette's syndrome.

References


Sotero de Menezes MA, Rho JM, Murphy P, Cheyette S: Lamotrigine-induced
tic disorder: report of five pediatric cases. Epilepsia 2000;
41:862-867[CrossRef][Medline]
Lombroso CT: Lamotrigine-induced tourettism. Neurology 1999;
52:1191-1194[Abstract/Free Full Text]
Cheung H, Kamp D, Harris E: An in vitro investigation of the action of
lamotrigine on neuronal voltage-activated sodium channels. Epilepsy Res
1992; 13:107-112[CrossRef][Medline]
Singer HS, Hahn IH, Moran TH: Abnormal dopamine uptake sites in
postmortem striatum from patients with Tourette's syndrome. Ann
Neurol 1991; 30:558-562[CrossRef][Medline]

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