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.