Pharmacokinetic/pharmacodynamic considerations for epilepsy - depression comorbidities.
BACKGROUND
Epilepsy may be frequently associated with psychiatric disorders and its co-existence with depression usually results in the reduced quality of life of patients with epilepsy. Also, the efficacy of antiepileptic treatment in depressed patients with epilepsy may be significantly reduced.


METHODS
Results of experimental studies indicate that antidepressants co-administered with antiepileptic drugs may either increase their anticonvulsant activity, remain neutral or decrease the protective action of antiepileptic drugs in models of seizures. Apart from purely pharmacodynamic interactions, pharmacokinetic mechanisms have been proven to contribute to the final outcome. We report on clinical data regarding the pharmacokinetic interactions of enzyme-inducing antiepileptic drugs with various antidepressants, whose plasma concentration may be significantly reduced. On the other hand, antidepressants (especially selective serotonin reuptake inhibitors) may influence the metabolism of antiepileptics, in many cases resulting in the elevation of plasma concentration of antiepileptic drugs.


CONCLUSIONS
The preclinical data may provide valuable clues on how to combine these two groups of drugs - antidepressant drugs neutral or potentiating the anticonvulsant action of antiepileptics are recommended in this regard. Avoidance of antidepressants clearly decreasing the convulsive threshold or decreasing the anticonvulsant efficacy of antiepileptic drugs (f.e. bupropion or mianserin) in patients with epilepsy is recommended.
a Experimental Neuropathophysiology Unit, Department of Pathophysiology , Medical University , Lublin , Poland.
Monika
M
Banach
a Experimental Neuropathophysiology Unit, Department of Pathophysiology , Medical University , Lublin , Poland.
Monika
M
Popławska
b Faculty of Health Sciences , High School of Economics, Law and Medical Sciences , Kielce , Poland.
Barbara
B
Błaszczyk
a Experimental Neuropathophysiology Unit, Department of Pathophysiology , Medical University , Lublin , Poland.
Kinga K
KK
Borowicz
c Department of Pathophysiology , Medical University , Lublin , Poland.|d Department of Physiopathology , Institute of Rural Health , Lublin , Poland.
Stanisław J
SJ
Czuczwar
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D003863:Depression / Q000150:complications / Q000188:drug therapy*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004347:Drug Interactions; D004827:Epilepsy / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D011788:Quality of Life
D000927:Anticonvulsants; D000928:Antidepressive Agents
Antiepileptic drugs; antidepressant drugs; depression; epilepsy; pharmacodynamics; pharmacokinetics