Epilepsy & Behavior 10 (2007) 268–271

www.elsevier.com/locate/yebeh

q
Anticonvulsants in sports: Ethical considerations
Kenneth R. Kaufman *

Departments of Psychiatry and Neurology, UMDNJ—Robert Wood Johnson Medical School, 125 Paterson Street,
Suite 2200, New Brunswick, NJ 08901, USA

Received 10 October 2006; revised 4 December 2006; accepted 8 December 2006

Available online 26 January 2007

Abstract

Objective. Antidoping codes in sport are intended to deter and sanction athletes using performance-enhancing agents while promoting
an even playing field for all competitors. Although the World Anti-Doping Code (WADC) permits anticonvulsants in general, harmoniza-
tion of antidoping permits an international sport federation (IF) to prohibit specific medications within that IF. The anticonvulsants
levetiracetam, tiagabine, and lamotrigine may pose ethical dilemmas and could be considered violations of antidoping codes.
Method. This study is a literature review with analysis.
Results. Lamotrigine, with antiglutamatergic and sodium channel properties, is FDA-approved for maintenance treatment of bipolar
disorder, in addition to its use in the treatment of major depression, anxiety disorders, and schizophrenia. Tiagabine, a selective GABA
reuptake inhibitor, has mood-stabilizing and anxiolytic properties. Levetiracetam, whose unique mechanism involves the modulators
b-carboline and zinc, has anxiolytic and mood-stabilizing properties. Anxiolytics, antidepressants, and antipsychotics are banned in
archery; under strict liability, all three anticonvulsants violate WADC/IF for that specific sport and could result in disqualification unless
therapeutic use exemptions (TUEs) are obtained. Ethical issues regarding the use of anticonvulsants by athletes and the need to obtain
TUEs are addressed.
Conclusion. The WADC with harmonized IF policies are meant to prevent doping by athletes, but not appropriate medical treatment.
When anticonvulsants have other psychotropic properties, ethical issues arise. Athletes should list all medications taken with diagnoses,
obtain TUEs as indicated, and contact the appropriate IF or Olympic organization to determine the status of the proposed medication
(banned, restricted, nonbanned). Further, clinicians should be knowledgeable regarding these issues when treating athletes.
Ó 2006 Elsevier Inc. All rights reserved.

Keywords: Anticonvulsants; Sports; Ethics; Doping; Epilepsy; Psychiatry; Treatment; Therapeutic use exemption; Levetiracetam; Tiagabine; Lamotrigine

1. Introduction athlete, violation of the spirit of sport, or if the substance

The key to amateur athletics is the concept that all par-
ticipants compete on an even playing field without the ben-
efit of performance-enhancing substances. For this
purpose, the World Anti-Doping Code (WADC) has been
created with far-ranging sanctions inclusive of simple
warnings, competition disqualification, and lifetime sus-
pensions [1]. The four main reasons for prohibiting sub-
stances are performance enhancement, danger to the
q
This paper was presented at the 7th European Congress on Epilep-
tology, Helsinki, Finland, July 2–6, 2006.
*
Fax: +1 732 235 7677.
E-mail address: kaufmakr@umdnj.edu
could serve to mask another prohibited substance (WADC
4.3) [1]. Fundamental to the WADC is the concept of strict
liability (WADC 2.1.1 and Comment 2.1.1) [1]. The athlete
takes personal responsibility for any and all substances that
might enter his or her body whether or not he or she know-
ingly ingested such. If the athlete tests positive for a prohib-
ited substance, whether she or he took such intentionally or
not, and even if that substance would have been detrimen-
tal and not enhancing to the athlete’s performance, so long
as that substance is listed as prohibited, the athlete is con-
sidered to have committed a doping offense and must suffer
the consequences. However, if a prohibited substance is
required for medical purposes, then the athlete can apply
for a therapeutic use exemption (TUE) [2].

1525-5050/$ - see front matter Ó 2006 Elsevier Inc. All rights reserved.
doi:10.1016/j.yebeh.2006.12.004
 K.R. Kaufman / Epilepsy & Behavior 10 (2007) 268–271
It is important for athletes and clinicians to realize that
the WADC list of prohibited substances is not all-inclusive
[3]. Specifically, the concept of ‘‘related substance’’ [specific
wording is ‘‘other substances with a similar chemical struc-
ture or similar biological effect(s)’’] exists in each category
to cover those substances with similar actions not yet clas-
sified. A recent ‘‘related substance’’ (stimulant) example is
modafinil, which resulted in disqualification, suspension,
and loss of medals for an elite female sprinter at the 2003
World Outdoor Track and Field Championships; the next
year, modafinil joined the list of prohibited substances [4].
Although the WADC permits anticonvulsants in gener-
al, harmonization of antidoping permits an international
sport federation (IF) to prohibit specific medications with-
in that IF. Archery prohibits antidepressants, anxiolytics,
and antipsychotics [5,6]. In competitive archery, the anti-
convulsants levetiracetam, tiagabine, and lamotrigine may
pose ethical dilemmas and could be considered violations
of antidoping codes. Further, if the competitive archer is
found to have committed a doping infraction, all sanctions
(including suspensions) imposed by FITA (the IF for
archery) are applicable to all signatories of WADC
(WADC 10.9 and 15.4), rendering an elite athlete potential-
ly ineligible for all athletic competitions [1].
2. Method
This study is a literature review with analysis.
2.1. Levetiracetam
Levetiracetam is a novel anticonvulsant whose unique mechanisms of
action and properties include inhibition of the negative allosteric modula-
tors zinc and b-carboline, reduction of potassium currents, selective block-
age of N-type calcium channels, and binding to the synaptic vesicle protein
SV2A [7–10]. Animal studies involving chlordiazepoxide withdrawal, the
modified plus-maze animal test, and the Vogel conflict test all supported
the anxiolytic properties of levetiracetam [11–13]. Further, levetiracetam
was found to be effective in the animal behavioral model of mania, pro-
ducing results similar to those of the known mood stabilizers lithium, val-
proate, and carbamazepine [14]. This study confirmed the stereospecificity
of levetiracetam in that the R-enantiomer was not effective in the treat-
ment of manic behavior [14]. Preliminary clinical studies noted the efficacy
of levetiracetam in adjunctive treatment of posttraumatic stress disorder
(PTSD) and in monotherapy treatment of social anxiety disorder
[15,16]. Further, preliminary reports have described the efficacy of leveti-
racetam in monotherapy and adjunctive treatment of refractory bipolar
disorders, including depressive, mixed, manic, and rapid cycling presenta-
tions [17–19].
2.2. Tiagabine
Tiagabine is a novel anticonvulsant whose mechanism of action as a
selective GABA reuptake inhibitor (SGRI) increases the level of functional
GABA in the synaptic cleft [20,21]. An animal study involving the elevated
plus-maze animal test revealed that acute and chronic administration of
tiagabine to rats had anxiolytic effects similar to those of acute administra-
tion of diazepam [22]. Further, cholecystokinin tetrapeptide-induced panic
and anxiety symptoms in healthy volunteers are reduced by tiagabine [23].
Clinical studies support the efficacy of tiagabine in monotherapy treatment
of both generalized anxiety disorder and panic disorder with agoraphobia
[24,25]. Efficacy in augmentation treatment of anxiety, treatment-resistant
269
anxiety, and PTSD has also been reported [26–29]. Preliminary findings
from a retrospective chart review suggest that adjunctive tiagabine may be
beneficial in reducing symptoms of rage and aggression associated with mul-
tiple psychiatric disorders [30]. An initial report on monotherapy tiagabine
treatment of major depression with anxiety suggests that tiagabine may have
antidepressant properties in addition to being an anxiolytic [31]. Literature
on the efficacy of tiagabine in bipolar disorder is mixed, though this may be
secondary to titration; a series of articles suggest that tiagabine may be ben-
eficial as an adjunctive treatment for bipolar disorder and even for schizoaf-
fective disorder [32–35].
2.3. Lamotrigine
Lamotrigine has multiple mechanisms of action and properties, some
believed to be more related to its efficacy as an anticonvulsant and others
more related to its efficacy as a psychotropic; these include antiglutamater-
gic, calcium channel-blocking, and sodium channel-blocking properties
[36–38]. Animal lamotrigine studies have addressed the antidepressant,
anxiolytic, and antimanic properties. Lamotrigine decreases immobility
time in the mouse forced swimming test consistent with antidepressant
effects [39]. The same study suggests that lamotrigine has postsynaptic 5-
HT1A receptor activity [39]. In the conditioned emotional response test
of anxiety in the rat, lamotrigine was noted to be anxiolytic with suggested
sodium channel mechanisms [40]. Lamotrigine as well as valproate and
carbamazepine are effective in the rodent model of mania [41].
Lamotrigine is FDA-approved for both the treatment of epilepsy and
the maintenance treatment of adults with Bipolar I disorder with a focus
on bipolar depression [42]. A series of retrospective chart reviews suggest
that lamotrigine is an effective augmenting agent for treatment-resistant
major depression [43–45]. A preliminary placebo-controlled randomized
trial noted the efficacy of lamotrigine in the treatment of PTSD [46].
Clinical studies also reveal that when used to augment clozapine, lamotri-
gine reduces positive symptoms of schizophrenia [47–49]. A small case
series reported the efficacy of lamotrigine monotherapy in the treatment
of borderline personality [50].
3. Discussion
Of the three anticonvulsants described in this article,
only lamotrigine is FDA-indicated for treatment in psychi-
atry. Nonetheless all three anticonvulsants have been used
off-label as monotherapy or adjunctive therapy for major
depression, bipolar disorder, generalized anxiety disorder,
panic disorder, PTSD, social phobia, impulse control
disorders, schizoaffective disorder, schizophrenia, and
borderline personality disorder.
Although anticonvulsants are not on the WADC pro-
hibited substance list, psychotropics are prohibited by
FITA [5,6]. Clearly, the anticonvulsants described in this
article have significant psychotropic properties. In light of
the WADC rule of strict liability for a prohibited or ‘‘relat-
ed substance,’’ this creates an ethical dilemma concerning
the use of anticonvulsants by athletes competing in
archery.
As anticonvulsants are not considered prohibited, it is
unlikely that an athlete with epilepsy competing in archery
would apply for a TUE. However, the literature supports
significant psychiatric comorbidity (especially anxiety and
mood disorders) in patients with epilepsy [51–54]. As anti-
convulsants are used to treat both epilepsy and psychiatric
disorders, it is quite possible that the patient with epilepsy
on a specific anticonvulsant is being treated for two disor-
270 K.R. Kaufman / Epilepsy & Behavior 10 (2007) 268–271
ders: the epilepsy for which the anticonvulsant is not
prohibited and the psychiatric disorder for which the
anticonvulsant should be considered a prohibited ‘‘related
substance’’ [55].
It is difficult to determine if an athlete has a specific ill-
ness and is being creative in his pharmacology to avoid
using a prohibited substance. Anticonvulsants have multi-
ple mechanisms of action and can treat multiple psychiatric
disorders. For competitive archers with anxiety and mood
disorders, use of anticonvulsants might be the ideal
approach to circumvent antidoping codes. Though this
article has addressed three specific anticonvulsants, nearly
all anticonvulsants have efficacy in psychiatric disorders.
Other anticonvulsants with positive therapeutic effects in
psychiatry include phenytoin, primidone, carbamazepine,
oxcarbazepine, divalproex sodium, gabapentin, topira-
mate, zonisamide, and pregabalin [56–69].
Does this then mean that no athlete with epilepsy taking
an anticonvulsant can participate in Olympic archery com-
petition? Does this mean that any archer taking an anticon-
vulsant has committed a doping infraction? If both World
Anti-Doping Agency (WADA) and FITA follow their
mandates, these are the ‘‘logical’’ but unfortunate conclu-
sions unless the athlete obtains a TUE.
The author recommends that all archers taking anticon-
vulsants obtain a TUE to ensure that there is no violation
of antidoping codes. Further, all athletes should clarify
with their individual IF and national Olympic organization
whether anticonvulsants or other medications are banned,
are banned specifically in their sport, or could be construed
as prohibited ‘‘related substances.’’ Athletes should list all
medications and diagnoses and have appropriate support-
ing medical documentation to obtain a TUE [4,70].
4. Conclusion
This article began with a narrow focus—ethical consid-
eration of three specific anticonvulsants in sports—and
found that use of these three anticonvulsants by competi-
tive archers could be a WADC violation. However, this
finding is not limited to these three anticonvulsants or even
anticonvulsants in general. All medications may have mul-
tiple mechanisms of action and often can be therapeutic for
multiple diagnoses with the potential for performance
enhancement. As such, greater clarity is required concern-
ing the concept of prohibited ‘‘related substance.’’ The pur-
pose of WADC with harmonized IF policy is to create an
even playing field by deterring utilization of performance-
enhancing substances, not to create an uneven playing field
by preventing athletes from obtaining appropriate medical
care. Further, WADC is not meant to be a medical arbiter,
deciding which medication is best for the patient. Athletes,
as patients, have responsibilities under WADC when tak-
ing prescribed medications. Athletes should list all medica-
tions and diagnoses, and obtain the necessary TUE with
the assistance of the treating clinician. Similarly, clinicians
need to be well informed of the WADC and its ramifica-
tions when treating athletes, as well as understand the pro-
fessional responsibilities associated with a TUE. Further
research and education are required in the complex field
of antidoping in sports medicine.
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