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Biomedical subjects

A Richens

Publications and source records attributed to A Richens.

At least 19 recordsLinked to original sources
PubMed1995

Double-blind comparison of lamotrigine and carbamazepine in newly diagnosed epilepsy. UK Lamotrigine/Carbamazepine Monotherapy Trial Group.

Lamotrigine has been licensed widely as adjunctive therapy for partial and secondary generalised seizures. Use of the drug as monotherapy was investigated in a double-blind, randomised, parallel-group comparison with carbamazepine in newly diagnosed epilepsy. After 4 weeks of planned, fixed dose escalation, doses were adjusted according to efficacy, adverse events, and plasma concentrations. 151 of 260 patients (131 lamotrigine, 129 carbamazepine) in eight UK centres completed the 48-week trial. No differences in efficacy between the drugs were found for partial seizures with or without secondary generalisation or for primary generalised tonic-clonic seizures. The proportion of patients maintained seizure-free during the last 24 weeks of treatment was almost the same in both groups (39% lamotrigine, 38% carbamazepine). More patients with primary generalised tonic-clonic seizures (47% both groups) than those presenting with a focal onset (35%, 37%) were fully controlled. Overall, fewer patients on lamotrigine than on carbamazepine withdrew because of adverse events (15 vs 27%). The commonest side-effect leading to withdrawal with either drug was rash (9%, 13%). Sleepiness was less common in lamotrigine than in carbamazepine recipients (12 vs 22%, p < 0.05). More lamotrigine than carbamazepine recipients (65 vs 51%, p = 0.018) completed the study (hazard ratio 1.57 [95% CI 1.07-2.31]). Lamotrigine and carbamazepine showed similar efficacy against partial onset seizures and primary generalised tonic-clonic seizures in newly diagnosed epilepsy. Lamotrigine, however, was better tolerated.

Adolescent↗
PubMed1995

Adjunctive treatment of partial seizures with tiagabine: a placebo-controlled trial.

Tiagabine is a new antiepileptic drug which acts by a novel mechanism, inhibiting the reuptake of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) into neurons and glia. A double-blind, placebo-controlled, crossover trial was undertaken, based upon a response-dependent design. Ninety-four patients with complex partial seizures with or without secondary generalised tonic-clonic seizures were recruited into an open screening phase and tiagabine was added to their existing drug therapy in doses titrated to reduce seizure frequency by > or = 25% or to the limit of tolerance. Forty-six responders were subsequently randomised to a double-blind crossover trial in which tiagabine was compared with placebo. Forty-two patients completed the trial. A significant reduction in the frequency of complex partial and secondary generalised tonic clonic seizures was seen. Twenty-six percent had a reduction of > or = 50% in the frequency of their complex partial seizures, and of the 27 patients who also had secondary generalised tonic clonic seizures, 63% experienced a reduction of > or = 50%. No interactions with baseline antiepileptic drugs were detected and no serious adverse reactions occurred. The commonest adverse events were tiredness, dizziness and headache. We conclude that tiagabine has promising antiepileptic effects. Further trials are underway.

Adolescent↗
PubMed1995

Psychiatric morbidity and psychodynamics of patients with convulsive pseudoseizures.

Forty-six female patients with pseudoseizures were compared with 50 female patients referred to a psychiatric outpatient clinic. Patients with convulsive pseudoseizures were more likely to be single and childless. An abnormal EEG was more frequently reported in patients with convulsive pseudoseizures, contributing to their earlier diagnosis of epilepsy. The defence mechanisms of patients with convulsive pseudoseizures using the Defense Mechanisms Inventory (DMI) were particularly characterized by higher scores on the 'reversal' scale and lower scores on the 'turning against self' scale. Mood disorders were more common in general psychiatric patients, while one-third of convulsive pseudoseizure patients did not complain of psychiatric symptoms.

Comorbidity↗
PubMed1995

Rational polypharmacy.

The development of assays for plasma antiepileptic drug concentrations has led to the discovery of many pharmacokinetic interactions, some causing drug intoxication and others resulting in ineffective drug concentrations. In the 1970s, a number of epileptologists began to argue that single drug therapy was desirable in the treatment of epilepsy and this has become the accepted policy when initiating therapy. About 75% of patients treated in this way will achieve remission with a minimum of adverse drug reactions. The remainder, however, continue to have unacceptable seizures and usually receive combinations of drugs. Evidence indicates that the response rate on adding a second drug is low, although in some studies of new drugs such as vigabatrin up to one-half of patients receiving add-on therapy experience a 50% or greater reduction in seizure frequency, and 10-15% are seizure-free in the short term. Unfortunately, randomized placebo-controlled studies have not been undertaken to compare the relative merits of monotherapy and combination therapy with respect of seizure control and adverse effects. It is argued that the time has come to do so, particularly in view of the known mode of action of some of the new drugs. Perhaps blocking excitation with one drug at the same time as enhancing inhibition with another may be better than doing only one or the other.

Anticonvulsants↗
PubMed1995

Pharmacokinetic and pharmacodynamic drug interactions during treatment with vigabatrin.

Pharmacokinetic drug interactions take place when one drug interacts with another at the level of metabolism, absorption or excretion. Pharmacodynamic interactions take place at the level of receptor sites, where they may have additive or potentiating effects. Vigabatrin is relatively free of pharmacokinetic interactions, and though it is associated with about a 20% decrease in serum levels of concomitantly administered phenytoin, the reduction is of little clinical significance. The mechanism underlying this effect is unknown. Because vigabatrin increases GABA-mediated inhibition in the brain (an action that is believed to account for its anticonvulsant effects), it might be expected to potentiate the CNS effects of benzodiazepines and alcohol. However, very sensitive eye movement studies have failed to detect any evidence of such an interaction. Overall, vigabatrin appears to be remarkably free of drug interactions. As a result, it is easier to use in clinical practice than older anti-epilepsy agents. Perhaps the most important finding of the interaction studies with vigabatrin is that there is no need for patients receiving the drug to be told to avoid alcohol.

Anticonvulsants↗
PubMed1994

Vigabatrin-induced psychosis--management problems.

A 22-year-old patient with partial seizures developed schizophreniform psychosis following the introduction of vigabatrin. She stopped her anticonvulsant medication as a consequence of her persecutory delusions. She subsequently suffered status epilepticus with severe brain damage. It is essential to outline a management plan for patients to detect and treat vigabatrin-induced psychosis.

Adult↗
PubMed1994

Safety of lamotrigine.

Clinical trials of lamotrigine (LTG) began in 1984. By November 1992 about 5,800 patient-years' experience of adverse effects had been compiled. In general, LTG has an acceptable safety profile. Mild central nervous system adverse effects such as ataxia, dizziness, and headache occur significantly more frequently with LTG than with placebo but seldom demand discontinuation of LTG therapy. Dosage-related allergic skin rash occurs in about 5% of patients. The rash rarely is severe enough to require hospitalization. The adverse-reaction profile of LTG compares favorably with that of traditional antiepileptic drugs.

Adult↗
PubMed1994

A multicentre comparative trial of sodium valproate and carbamazepine in adult onset epilepsy. Adult EPITEG Collaborative Group.

The long-term efficacy and safety of sodium valproate and carbamazepine in adult outpatients with newly diagnosed primary generalised or partial and secondarily generalised seizures were compared in a randomised, open, multicentre study at 22 neurology outpatient clinics. Patients were randomised to oral sodium valproate (Epilim EC enteric coated 200 mg tablets twice daily, n = 149) or oral carbamazepine (100 mg twice daily increasing to 200 mg twice daily in week 2, n = 151) and followed up for three years. If clinically necessary, dosages were regularly increased until seizures were controlled or toxicity developed. Sodium valproate and carbamazepine controlled both primary generalised and partial seizures equally effectively overall. Significantly more patients on sodium valproate than carbamazepine (126/140 (90%) v 105/141 (75%), p = 0.001) remained on randomised treatment for at least six months. Skin rashes occurred significantly more often in carbamazepine recipients than in sodium valproate recipients (11.2% v 1.7%, p < 0.05) and carbamazepine was associated with a higher withdrawal rate because of adverse events (15% v 5% on sodium valproate) in the first six months of treatment. There was no difference between the drugs in the rate of withdrawal because of poor seizure control at any stage, regardless of seizure type. At the end of the three year trial period, over 70% of the available patients were still on randomised treatment or had recently stopped treatment after achieving full seizure control. Sodium valproate and carbamazepine were both associated with a high degree of overall seizure control regardless of seizure type and both have good long-term tolerability in adult patients with newly diagnosed epilepsy. Recommendations are made for a higher initial dosage regime for sodium valproate in partial seizures.

Administration, Oral↗
PubMed1994

A risk-benefit assessment of vigabatrin in the treatment of neurological disorders.

Vigabatrin was designed to increase the levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the brain. It does this by replacing GABA as a substrate for the action of the catabolic enzyme GABA-transaminase. As a result of this inhibition, neuronal GABA levels are elevated, resulting in enhanced endogenous GABA transmission. A number of clinical trials assessing the effect of vigabatrin in epilepsy have been completed. Vigabatrin is of proven benefit in partial seizures and secondarily generalised tonic clonic seizures, and it is licensed for use as adjunctive therapy in these conditions in several European countries. It has been shown to be effective in some epilepsy syndromes in children including West's syndrome, infantile spasms and cryptogenic partial seizures. Its effect on primary generalised tonic clonic seizures is variable, while there is considerable evidence that it has a deleterious effect on myoclonic and absence seizures. There have been a few reports of the benefits of vigabatrin in other neurological disorders including tardive dyskinesia, degenerative ataxias and GABA metabolism disorders. The adverse effects associated with vigabatrin are similar to those seen with other anticonvulsants, with a predominance of CNS effects including somnolence, fatigue, irritability, dizziness and headache. Psychiatric symptoms including depression and psychosis are seen in a small number of patients and cause the most problems. These often necessitate discontinuation of vigabatrin, which usually results in resolution of symptoms.

4-Aminobutyrate Transaminase↗
PubMed1992

Performance of techniques for measurement of therapeutic drugs in serum. A comparison based on external quality assessment data.

Ten assay techniques were compared using measurements of a range of 15 drugs spiked in freeze-dried samples of serum reported to the Heathcontrol External Quality Assessment Scheme between November 1988 and January 1991. Three measures of performance were studied: frequency of outliers greater than 3 standard deviations from the sample mean, the coefficient of variation (CV) of sample measurements, and the difference of the sample mean from the spike value. The most consistently precise technique was polarisation fluoroimmunoassay (PFIA). It was in the group of techniques producing significantly fewer outliers and lower CVs than other techniques for all its target analytes. However, a specific interaction with the animal serum used as sample matrix resulted in significant negative bias in PFIA measurements of carbamazepine. Other immunoassay techniques and high-performance liquid chromatography also performed well for a range of analytes, in most cases giving less than 6% of outliers with CVs of less than 13% and less than 5% bias. The least satisfactory techniques were nephelometry and gas-liquid chromatography with derivatisation, which for several analytes gave significantly more outliers and higher CV values than other techniques. In samples containing carbamazepine-10, 11-epoxide, immunoassay measurements of carbamazepine showed cross-reactivity with the epoxide metabolite of between 7 and 15%.

Carbamazepine↗
PubMed1992

Bioavailability and dissolution of proprietary and generic formulations of phenytoin.

A comparative study of the bioavailability of seven formulations of phenytoin was carried out on 17 patients with epilepsy who were taking phenytoin regularly as part of their drug therapy. Three patients withdrew for personal reasons. No significant differences were found between Epanutin capsules and other generic formulations. However significant differences were noted between the generic products. Phenytoin BP tablets manufactured by Regent Laboratories (now withdrawn) had a relative bioavailability of only 76% compared with tablets manufactured by A H Cox and Company. In vitro dissolution tests requirements were met by all formulations of generic 100 mg tablets, and it was concluded that in vitro dissolution tests are not reliable indicators of biological equivalence. Significantly higher plasma levels were found with Epanutin Infatabs, but this was accounted for by their higher content of phenytoin, which is present in the acid form rather than the sodium salt.

Adolescent↗
PubMed1992

Lamotrigine as an add-on drug in the management of Lennox-Gastaut syndrome.

We report our experience with lamotrigine add-on therapy in the treatment of 11 patients with Lennox-Gastaut syndrome. Lamotrigine is a novel antiepileptic drug, chemically unrelated to the major anticonvulsants in current use. Ten patients experienced a > 50% reduction in seizure frequency, 1 patient experienced no change in seizure frequency. All patients tolerated lamotrigine satisfactorily and no side-effects were reported.

Anticonvulsants↗
PubMed1991

The influence of age on the pharmacokinetics of the antiepileptic agent oxcarbazepine.

The disposition of oxcarbazepine was studied in 12 young and 12 elderly healthy male and 12 young and 12 elderly healthy female volunteers, with emphasis on the influence of age. Oxcarbazepine was administered as a single dose of either 300 mg (men) or 600 mg (women), followed by multiple-dose (300 mg) administration twice a day for 7 days (men) or 6 days (women). Semilogarithmic plasma concentration-time curves showed an increasing decline at decreasing concentrations. Accumulation of the pharmacologically active metabolite monohydroxycarbamazepine was found to be more than one would anticipate on the basis of linear and unchanged pharmacokinetics. Saturation did not seem to occur at the level of renal excretion. No apparent differences between male and female volunteers were observed. A significant higher maximum concentration, higher area under the curve parameters, and a lower elimination rate constant were observed in the elderly. These observations are in line with a smaller renal clearance of monohydroxycarbamazepine in the elderly group. In a clinical situation, these age-related differences are not likely to have important implications. In general, treatment with oxcarbazepine was well tolerated.

Adolescent↗