The possibility that cognitive impairment may develop as a consequence or aftermath of epilepsy was raised as early as 1885 when Gowers described ‘epileptic dementia’ as an effect of the pathological sequela of seizures. Nonetheless, the topic was not coupled to antiepileptic drug treatment until the 1970s. It has now been established that antiepileptic drug treatment may be associated with a variety of side-effects. Some effects appear immediately after the start of drug exposure, such as nystagmus, but are relatively benign because they show habituation, or are reversible when they are dose dependent. Others may be of insidious onset, emerging only after extended periods of …
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The interest in the cognitive side-effects of antiepileptic drug treatment is of relatively recent origin and the first studies are from the 1970s,probably stimulated bythe widening range of possibilities for drug treatment during that period; valproate and carbamazepine were clinically introduced in this same period and many studies compare these drugs with phenytoin (combination of phenytoin). A first paragraph of this chapter reviews the literature in lines of evidence-based medicine, that is, reviewing the empirical data that were published in peer-reviewed journals. Potentially relevant studies were identified through computerized and manual searches of the English-language literature published from January 1970 through December 1994. A computerized …
[ Continue Reading... ]Although the psychometric studies generally show a tendency of cognitive impairments in polytherapy compared to monotherapy, this merely suggests a drug interaction effect. As previously mentioned evidence-based confirmation will be extremely difficult due to the methodological problems that occur when studying polytherapy and especially in the light of the many interfering factors, especially the seizure confound. Any study will have difficulties entangling the interfering factors of seizure effects and the effects of polytherapy, when typically polytherapy is used in the more refractory epilepsies. Nonetheless, we may look at more anecdotal clinical information. In many drug trials a similar effect has been found as suggested by the psychometric studies: a higher incidence …
[ Continue Reading... ]We can take this one step further and use the subjective patient complaints as primary outcome measure. This has not been done systematically. We have, however, recently finished a community-based study, using subjective patient complaints about side effects of their treatment as primary outcome measure. Table Subjective reported side effects in 346 patients in a community-based study Area and type of side effect” % patients6 General central nervous system 68.2 (overall central nervous system complaints) Fatigue 20.3 Tiredness 18.8 General slowing 12.1 Headache 8.9 Dizziness 8.1 Motor problems 31.5 (overall motor complaints) Tremor 13.3 Ataxia 13.0 Falling 5.2 Gastrointestinal complaints 33.2 (overall gastrointestinal complaints) Weight gain 12.4 Micturition problems 8.4 Loss …
[ Continue Reading... ]In 1978 Penry remarked ‘The clinical management of epilepsy has improved dramatically in the past decade through the determination of serum antiepileptic drug concentrations’ . The recommendations for undertaking therapeutic drug monitoring of antiepileptic drugs in serum are based on clinical experience and on a number of studies demonstrating a correlation between serum concentrations of antiepileptic drugs on the one hand, and seizure frequency and dose-dependent adverse effects on the other hand. …
[ Continue Reading... ]The applicability of therapeutic drug monitoring during combination therapy with different antiepileptic drugs or during combination of an antiepileptic drug and drugs used for the treatment of non-epilepsy-related conditions relates to three main considerations, which are discussed below. Table Indications for the determination of antiepileptic drugs in serum • Therapeutic unresponsiveness (the determination of antiepileptic drugs in serum helps to clarify the causes of the resistance to therapy, a frequent cause being irregular intake or underdosage; deliberate overdosage due to fear of seizures can also be detected) • Suspected non-compliance • Lack of communication (e.g. infants, foreign-language patients, …
[ Continue Reading... ]Introduction: antiepileptic drugs in non-epileptic conditions Ever since they first appeared, antiepileptic drugs have not infrequently been used to treat patients with conditions other than epilepsy. Some antiepileptic drugs, e.g. phenytoin (combination of phenytoin), carbamazepine and valproic acid (valproate), have for long been indicated in a number of neurological and psychiatric disorders. The same is true for some of the new generation antiepileptic drugs, such as gabapentin, lamotrigine, levetiracetam,oxcarbazepine,tiagabine,topiramate and pregabalin. It seems that newer antiepileptic drugs …
[ Continue Reading... ]In pregnant women serum propranolol concentrations are increased by 50%. However, in hypertensive pregnant women treated with 90 mg of phenobarbital, a significant decrease in serum propranolol concentration has been observed, thus suggesting that pregnancy alters the half-life of propranolol therapy associated with phenobarbital. It has also been reported that clearance of lamotrigine in pregnancy may be increased. Moreover, in one study lamotrigine plasma concentrations were slightly lower in females (13.7%) than in males. However, in another study this difference was not confirmed. Combination of phenobarbital and theophylline results in increased theophylline clearance in children and adults but not in premature neonates. Serum concentration of tirilazad mesylate (a membrane lipid peroxydation …
[ Continue Reading... ]Carbamazepine Carbamazepine is one of the most commonly used antiepileptic drugs in epilepsy and other neurological and psychiatric disorders. Carbamazepine mechanisms involve inhibitory action on sodium and on calcium (L- and N-type) channels, inhibitory effect on the release of somatostatin, increase of 5-HT release, effect on synaptic transmission and receptors, purine, monoamine, acetylcholine, adenosine and NMDA receptors. Its broad spectrum of pharmacological actions may explain the potent effect of carbamazepine in disorders other than epilepsy. The analgesic effect is most comprehensively documented in neuralgias. However, it is also used in diabetic polyneuropathy, phantom limb pain syndrome, thalamic pain, cerebellar tremors and migraine. There are reports that carbamazepine is also effective …
[ Continue Reading... ]Classification of psychotropic drugs Antidepressant drugs Everybody is familiar with the tricyclic antidepressant drugs. However, in recent years a number of newer antidepressant drugs have been introduced into clinical practice (Table Classification of the psychotropic drugs currently in use). Essentially these are mainly non-tricyclic, earlier variants included mianserin, maprotiline and viloxazine. The selective serotonin re-uptake inhibitors are represented by citalopram, fluoxetine, fluvoxamine, sertraline and paroxetine. Of these, citalopram is the most selective on serotonergic uptake, inhibiting serotonin uptake 3000 times more than noradrenaline uptake, and 22 000 …
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