Felbamate monotherapy has stimulant-like effects in patients with epilepsy

Ketter, T.A.; Malow, B.A.; Flamini, R.; Ko, D.; White, S.R.; Post, R.M.; Theodore, W.H.

« Previous Next »Epilepsy Research
Volume 23, Issue 2 , Pages 129-137, March 1996

Felbamate monotherapy has stimulant-like effects in patients with epilepsy☆

T.A. Ketter
- Corresponding author. Biological Psychiatry Branch, NIMH, Building 10, Room 3N212, 9000 Rockville Pike, Bethesda, MD 20892, USA. Tel.: (301) 496-6826; fax (301) 402-0052.
- Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, MD, USA
B.A. Malow
- Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
R. Flamini
- Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
D. Ko
- Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
S.R. White
- Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
R.M. Post
- Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, MD, USA
W.H. Theodore
- Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA

Received 27 March 1995; received in revised form 15 August 1995; accepted 15 September 1995.

Abstract

The objective of this study was to assess the psychiatric effects of the antiepileptic drug (AED) felbamate (FBM) in patients with epilepsy. FBM is a new AED with a novel putative (antiglutaminergic) mechanism. Older AEDs such as carbamazepine and valproate have psychotropic properties, but the psychiatric effects of FBM and other new antiglutamatergic AEDs remain to be determined.

Thirty inpatients with refractory epilepsy were openly tapered off all AEDs in conjunction with intensive presurgical monitoring prior to a two week randomized double-blind parallel trial of FBM monotherapy versus placebo, followed by open FBM therapy. Psychopathology was rated with weekly psychiatric rating scales. Anxiety, depression and seizures increased significantly with AED discontinuation. Acute blind FBM monotherapy yielded antiepileptic and stimulant-like effects (insomnia, anorexia, and anxiety), but failed to influence AED withdrawal-emergent psychopathology. Restarting original AEDs resolved such pathology in FBM drop outs. Chronic open FBM also had stimulant-like effects, with half of the patients displaying psychiatric deterioration and the other half modest improvement compared to baseline therapies. Baseline insomnia and anxiety may be markers for poorer psychiatric responses to chronic open FBM.

FBM had stimulant-like effects, lacked anxiolytic effects, and failed to attenuate AED withdrawal-emergent psychopathology. Baseline insomnia or anxiety may predict poorer psychiatric responses to FBM. Further studies are required to assess whether the novel psychiatric effects observed with FBM also occur with other new antiglutamatergic AEDs.

Keywords: Anticonvulsant, Psychotropic medication, Drug withdrawal, Anxiety, Depression

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