The Mechanism of Carbamazepine Aggravation of Absence Seizures

@article{Liu2006TheMO,
  title={The Mechanism of Carbamazepine Aggravation of Absence Seizures},
  author={Lige Liu and Thomas W. Zheng and Margaret J. Morris and Charlott Wallengren and Alison L. Clarke and Christopher A. Reid and Steven Petrou and Terence J. O'Brien},
  journal={Journal of Pharmacology and Experimental Therapeutics},
  year={2006},
  volume={319},
  pages={790 - 798}
}
Carbamazepine (CBZ) aggravates many generalized seizures types, particularly absence seizures, but the mechanisms underlying this are poorly understood. GABA signaling within the reticular nucleus (Rt) and the ventrobasal complex (VB) of the thalamus is critical to the neurophysiology of absence seizures. The hypothesis that CBZ aggravates absence seizures by acting at the VB thalamus via a GABAA receptor-mediated mechanism was investigated in a genetic rat model, generalized absence epilepsy… 

Figures from this paper

Carbamazepine aggravates absence seizures in two dedicated mouse models.

Seizure Aggravation—Evidence that Oxcarbazepine Requires Monitoring

TLDR
It is suggested that OXC can aggravate seizures and/or worsen EEG features in children following initiation of therapy with OXCs, and monitoring of patients with follow-up EEGs may be important, especially in patients who do not show adequate response to therapy.

Bipolar Disorders and Carbamazepine: Pharmacokinetics,Pharmacodynamics, Therapeutic Effects and Indications of Carbamazepine: Review of Articles

TLDR
Carbamazepine is a mood stabilizer which is approved for use in bipolar disorder with manic and mixed episodes and for the treatment of trigeminal neuralgia, temporal lobe epilepsy and generalized tonic-clonic seizure.

Aggravation of absence seizure related to levetiracetam.

Aggravation of electroencephalographic features in an epileptic child treated by oxcarbazepine monotherapy : A case report and review of the literature

TLDR
OXC may induce new types of seizure and aggravate EEG features although it is considered to be the first-line anti-epileptic drug(AED) and much better tolerated than either phenytoin or CBZ.

Eslicarbazepine acetate for the treatment of focal epilepsy: an update on its proposed mechanisms of action

TLDR
Preclinical findings may suggest the potential for antiepileptogenic effects; furthermore, the lack of effect upon KV7.2 outward currents may translate into a reduced potential for eslicarbazepine to facilitate repetitive firing.

Long-Term Valproate Treatment Increases Brain Neuropeptide Y Expression and Decreases Seizure Expression in a Genetic Rat Model of Absence Epilepsy

TLDR
It is demonstrated that long-term valproate treatment results in an upregulation of thalamic expression of NPY implicating this as a potential contributor to the mechanism by whichValproate suppresses absence seizures.

Gr upSM Underestimated Aspects of Epilepsy Treatment : Forced Normalization and Seizure Aggravation by Antiepileptic Drugs

TLDR
Although there is no consensus about the therapeutic approach, most investigators recommend reassessment of the type and dose of AEDs and a possible brief course of treatment with antipsychotics and antidepressants.
...

References

SHOWING 1-10 OF 41 REFERENCES

Aggravation of Absence Seizures by Carbamazepine in a Genetic Rat Model Does Not Induce Neuronal c-Fos Activation

TLDR
The association between increased neuronal activation in the Rt and seizure burden in GAERS provides further support for the critical role of this structure in the maintenance, but not initiation, of absence seizure activity.

Carbamazepine pharmacokinetics-pharmacodynamics in genetically epilepsy-prone rats.

Pathophysiological mechanisms of genetic absence epilepsy in the rat

Selective Susceptibility to Inhibitors of GABA Synthesis and Antagonists of GABAA Receptor in Rats with Genetic Absence Epilepsy

TLDR
An abnormal cortical GABAergic activity may underlie absence seizures in GAERS, a selected strain of Wistar rats that occur spontaneously in genetic absence epilepsy rats from Strasbourg.

A Model of Chronic Spontaneous Petit Mal‐like Seizures in the Rat: Comparison with Pentylenetetrazol‐Induced Seizures

TLDR
It is suggested that the Wistar rats displaying spontaneous seizures constitute a valid physiological and pharmacological model of petit mal absences, presenting advantages compared to the usual models in which seizures are induced byinjected epileptogenic drugs.

Antiepileptic drug evaluation in a new animal model: spontaneous petit mal epilepsy in the rat.

TLDR
The hypothesis that Wistar rats' recurrent seizures constitute a valid pharmacological model of petit mal epilepsy is confirmed and its predictive value appears to be superior to that of other currently used models.

Genetic absence epilepsy in rats from Strasbourg--a review.

TLDR
Neurophysiological, behavioural, pharmacological and genetic studies demonstrate that spontaneous SWD in GAERS fulfill all the requirements for an experimental model of absence epilepsy.

Intracerebroventricular pertussis toxin enhances sensitivity to chemical convulsants and decreases the protective efficacy of carbamazepine in mice.

TLDR
The observations suggest that the enhanced sensitivity to a number of chemical convulsants irrespective of their mode of action possibly results from a functional suppression of inhibitory transmission at receptors coupled to pertussis toxin sensitive G proteins, rather than a direct action on G protein linked excitatory neurotransmission.

Seizures Induced or Aggravated by Anticonvulsants

TLDR
Six cases of epileptic children are reported, in whom anticonvulsant therapy, aggravated rather than controlled the seizures or induced minor seizures, which is apt to occur particularly in certain types of childhood epilepsy that are refractory to therapy and are accompanied by slow spike‐wave discharges in the EEG, such as the Lennox‐Gastaut syndrome.