Low Risk of Development of Substance Dependence for Barbiturates and Clobazam Prescribed as Antiepileptic Drugs: Results from a Questionnaire Study

Abstract

There is no systematical research about the topic of dependence on antiepileptic drugs (AED) for patients with epilepsy, despite the fact that barbiturates and benzodiazepines comprise a potential risk of dependence. We hypothesize that there is no psychological substance dependence for patients with epilepsy, possibly because of their outcome expectations. The aim of the study was to examine these patients in terms of substance dependence. One hundred inpatients at the Lake Constance Epilepsy Center were asked about their experiences with AED in terms of dependence in a structured interview. We registered general statements about dependence of AED, markers for substance dependence, and outcome expectations. About 50% of the patients reported withdrawal symptoms and the development of tolerance, but less than 10% noticed loss of control and craving. Withdrawal symptoms and development of tolerance were significantly lower in a group of patients without barbiturates or clobazam versus patients with barbiturates or/and clobazam. There was no significant difference between these two groups in psychological criteria of dependence, that is, loss of control and craving. Outcome expectations of AED were clearly related to the efficacy against seizures, and only to a small amount to psychotropic effects. The study demonstrates that physiological variables of dependence are present more in patients with epilepsy with a permanent intake of barbiturates or clobazam, but psychological variables of dependence are rarely present in epileptic patients, with or without an intake of barbiturates and clobazam. These results confirm our hypothesis that substance dependence is not a major problem in benzodiazepines and barbiturates in patients with epilepsy. Outcome expectations seem to be related mainly to the anticonvulsant and not the psychotropic effect. This might be the reason for the absence of dependence.

Synthesis, Crystal Structure and DFT Studies of 1,3-Dimethyl-5-propionylpyrimidine-2,4,6(1H,3H,5H)-trione

“…Other pyrimidinetrione derivatives, including bisoxadiazole and bisthiadiazole moieties, have been used as antibiotic and antifungal agents [9]. Pyrimidinetriones also belong to a broad group of drugs used as anticonvulsant, narcotic, sedative, antiepileptic, and antitumor agents [10][11][12][13]. They have found a prominent place in pharmaceutical industry because of their biochemical effects on calcium, acetylcholine, biogenic amines (Serotonin, Norepinephrine, Dopamine and Histamine), glutamate, aspartate and gamma-aminobutyric acid for the excitation-secretion coupling process involved in neurotransmitter release [14].…”

Synthesis, Characterization, and Tautomerism of 1,3-Dimethyl Pyrimidine-2,4,6-Trione s-Triazinyl Hydrazine/Hydrazone Derivatives

“…Their most remarkable action is on the central nervous system. They are extensively used for producing effects ranging from mild sedation to anaesthesia [17][18][19][20][21] as anticonvulsants, anxiolytics, sedative, and antiepileptic agents, as well as antitumoral agents [22][23][24][25][26]. They have found a prominent 2 Journal of Chemistry place in pharmaceutical industry because of their biochemical effects on calcium, acetylcholine, biogenic amines, glutamate, aspartate, and gamma-aminobutyric acid [27].…”

Non-catalytic multicomponent rapid and efficient approach to 10-(2,4,6-trioxohexahydropyrimidin-5-yl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-ones from salicylaldehydes, dimedone, and barbituric acids

“…They are also effective as anxiolytics and as anticonvulsants [13]. The current interest in barbiturates arises from their pharmacological potential as analeptics, immunomodulating and anti-AIDS agents, and also as anticancer remedies [14].…”