New Perspectives to the
Use of Anticonvulsant Medication in Neuropsychiatry
Vernon M Neppe MD, PhD
Educational Objectives
- To educate in the area of epilepsy demonstrating
the difficulties of research and clinical practice.
- To discuss the clinical implications with regard
to management options and problems.
- To discuss the role of firing and chemistry in
the brain and its parallels with seizures, kindling
and neuromodulation.
- To educate in the areas of anticonvulsant use and
their appropriate prescription.
- To evaluate information relating to possible applications
of anticonvulsants in neuropsychiatry including mania,
dyscontrol, non-responsive psychosis, neuralgia, migraine
and atypical headaches.
ABSTRACT
The use of anticonvulsants have primary indications
for epilepsy. They have become complicated enough for
the development of the specialty of epileptology to
have developed. They are not homogeneous in action,
structure, mechanism and indication. These drugs have
become a frequent generally non-approved addition to
the armamentarium of the psychiatrist. Their psychiatric
applications may apply to as much as half of their use.
The anticonvulsants are not interchangeable and they
differ considerably in side-effects and the specific
subtypes of seizure disorder that they control. They
also vary in possible use in the non-epileptic setting
as well. Frequently these neuropsychiatric conditions
are not well-defined in the context of diagnostic framework
for aggression in the Diagnostic and Statistical Manual
III revision or DSM-IV.
Anticonvulsants can be divided into two major functional
groups:
- The older, well tested ones such as Phenobarbital
and primidone (which have little use today because
of their side-effect profile), phenytoin (Dilantin)
(which has limited use outside seizure disorders because
of its toxicity potential) and carbamazepine (Tegretol)
and valproate (Depakote, Epilim) (which have formed
the backbone of modern anticonvulsant therapy in epilepsy
and beyond to various other neurological and psychiatric
uses).
- The newer anticonvulsants which are exciting but
far less tested and on which there is virtually no
data as to psychiatric applications. These drugs are
all technically marketed in the United States as "adjunctive
anticonvulsants" as the studies examined them as adjunctive
therapy to such standards as carbamazepine, valproate
and phenytoin. Already such drugs as felbamate (Felbatol)
have proven potentially dangerous hemopoetically,
and an apparently safe drug with limited side-effects
- gabapentin (Neurontin) was perceived as limited
in effectiveness, but this is changing as dosing is
increasing with the drug. Lamotrigine (Lamictal) ,
Tiagabine (Gabitril) and Topiramate (Topamax) may
turn out to have interesting applications and are
ripe for further research.
Carbamazepine has potential in the non-indicated management
of episodic disorders particularly those linked with
hostility. Preliminary research suggests its use is
particularly apposite in "Paroxysmal Neurobehavioral
Disorders" as a proto type organic illness with
epilepsy like phenomena. The mechanism may be via a
limbic antikindling effect. Its use in conditions as
mania and neuralgic pain may be via different mechanisms.
Valproate is the broadest spectrum anticonvulsant
that we know of and the one which has the least side-effects
of the first line anticonvulsants: less sedation, hemopoetic
consequences and neurotoxicity than carbamazepine and
an effectiveness in both grand mal and petit mal seizures.
It is effective in both partial and generalized seizures.
Psychiatrically its the only anticonvulsant approved
for any condition - in this instance mania, and its
use in headache particularly refractory headache and
migraine are exciting possibilities.
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