Ambiguous results of an attempt to withdraw barbiturates in epilepsy patients with intellectual disability

Abstract

Phenobarbital and primidone frequently have adverse effects on mental functions. Therefore, an attempt was made to taper barbiturates in 85 patients out of a resident population with epilepsy and intellectual disability who were selected according to clinical criteria. The objectives were to reduce the use of barbiturates, to improve the patients' cognitive and psychological state, and to reduce polypharmacy while avoiding seizure exacerbation. Four months after complete withdrawal changes in seizure frequency were assessed as well as changes in cognitive abilities, psychological state and behaviour (using the clinical global impression scale). In 13 patients the tapering failed due to complications (seizure increase in 11 patients). In 72 patients the barbiturate was completely withdrawn (mean duration of tapering: 393 days). Cognitive improvement was achieved in 17 patients (23.6%), 5 patients (6.9%) deteriorated. Seizure frequency remained unchanged in 33 patients (45.8%), in another 15 patients (20.8%) the seizure frequency decreased. Reduction in polypharmacy was obtained in 61 patients (84.7%). In an overall judgement (clinical global impression scale) of cognitive abilities AND seizure control, 25 patients (34.7%) were improved. 31 patients (43.1%) remained unchanged while 12 patients deteriorated (4 patients: impossible to judge). For statistical analysis three outcome groups were defined: the improved group (N=25), the unchanged group (N=31), and the deteriorated/failed group (N=25) consisting of the 12 deteriorated patients plus the 13 patients in whom tapering failed. Stepwise logistic regression revealed a history of an attempt to withdraw phenobarbital/primidone (p=0.017; OR 3.8), age (p=0.012) and seizure frequency (marginally significant: p=0.097) as outcome predictors. Older age was associated with better outcome. A high seizure frequency before tapering was related to good outcome, while seizure freedom and a history of failed withdrawal were associated with deterioration/failure. Outcome did not depend on duration of barbiturate therapy, dosage or serum concentration, co-medication, reduction rate, degree of intellectual disability, or epilepsy syndrome. In summary, the number of barbiturate medications has been considerably reduced, but the principal aim of the project, to relieve patients from assumed barbiturate side effects, has been achieved only in one out of four patients.

A comparison of antiepileptic drug therapy in patients with severe intellectual disability and patients with normal intellect

“…These attempts were usually associated with an increase in seizure frequency or change in behavior that was not accepted by the family (data not shown). This observation is supported by studies in which attempted tapering of barbiturates or BZDs in epilepsy patients with ID failed (leading to a deterioration in seizure control or cognitive ability) [32,33]. Importantly, our findings do not provide any evidence for a discrepancy in access to novel pharmaceutical seizure treatments in patients with ID.…”

Treatment of behavioral problems in intellectually disabled adult patients with epilepsy

“…A careful clinical history might reveal a particular pattern of behavior worsening related to seizure occurrence; in this case improving seizure control might result in improvement of behavior. In other cases an antiepileptic drug might be suspected of causing or worsening a patient's behavior, either because it is known to cause this type of side effect (especially barbiturates and benzodiazepines), or because there is a relationship with the time of introduction of the new agent and the onset of behavior derangement or worsening (Huber et al., ).…”

The influence of sulfur substituents on the molecular geometry and packing of thio derivatives ofN-methylphenobarbital

“…Barbiturates are a widespread group of compounds with various pharmacological activities. In particular, phenobarbital, thiopental and pentobarbital have been the subjects of extensive research due to their anaesthetic, sedative, hypnotic, amnesiac and anticonvulsant properties (Kushikata et al, 2003;Huber et al, 2009). The structures of numerous barbituric acid derivatives, such as phenobarbital, have been studied with respect to their ability to form polymorphs (Williams, 1973(Williams, , 1974Platteau et al, 2005;Day et al, 2007).…”