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.
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 (which has limited use outside
seizure disorders because of its toxicity potential)
and carbamazepine and valproate (which form the backbone
of modern anticonvulsant therapy in epilepsy and beyond).
-
The newer anticonvulsants which are exciting but far
less tested and on which there is virtually no data as to
psychiatric applications. Already such drugs as felbamate
have proven potentially dangerous hemopoetically, and
the converse safest drug - gabapentin is limited in
effectiveness. Lomotrigine and felbamate may turn out
to have interesting applications.
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.
|