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.