Phenobarbital withdrawal seizures may occur over several weeks before remitting: Human data and hypothetical mechanism

Bidlack, Jean M.; Morris, Harold H.

doi:10.1016/j.seizure.2008.06.014

Cited by 7 publications

(5 citation statements)

References 15 publications

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“…Therefore, the confounding effect of concomitant medication could not be avoided in our series and reflects real-life epileptological practice. Discontinuation of other AEDs with a long half-life similar to that of phenobarbital can cause withdrawal symptoms and withdrawal seizures [4]. This might be explained by alterations of the hippocampal GABA receptors long after therapy has ended [12] which should not be an issue with PER and its specific mode of action.…”

Section: Discussionmentioning

confidence: 99%

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Clinical experience of abrupt discontinuation of perampanel: a case series

Blickhan

Intravooth

Staack

et al. 2021

Epileptic Disorders

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With an elimination half-life of 105 hours, perampanel (PER) allows a once-daily dosing regimen. In pivotal trials, when PER was tapered, it was therefore usually discontinued abruptly. Thus, in our hospital we have always practiced abrupt cessation. In this case series, we investigated how long PER serum concentrations still remain measurable after abrupt discontinuation of PER and whether withdrawal symptoms, such as an increase in seizures or status epilepticus, occur. PER serum levels and the clinical course of 15 adult in-patients were monitored for three weeks based on a retrospective study design following abrupt discontinuation of PER. After one week, PER was still detected in 13 of 15 patients, after two weeks in 10, and after three weeks in three. Neither a severe increase in seizure frequency nor status epilepticus occurred. However, modifications of the concomitant antiseizure drugs were necessary. The abrupt discontinuation of PER leads to a slow decrease in plasma concentration, thus resembling self-evident gradual discontinuation of PER. In some cases, PER may still be measurable and thus clinically active even weeks after its discontinuation. Efficacy and safety of other antiseizure drugs can be estimated appropriately only thereafter.

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Section: Discussionmentioning

confidence: 99%

“…Discontinuation of ASDs with a long half‐life ( e.g . phenobarbital) typically causes an increase in seizure frequency several days up to weeks after discontinuation [4]. Experiences with other ASDs with a long elimination half‐life, such as bromides, topiramate or zonisamide, are scarce.…”

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confidence: 99%

Clinical experience of abrupt discontinuation of perampanel: a case series

Blickhan

Intravooth

Staack

et al. 2021

Epileptic Disorders

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“…[191,188] The mechanism of barbiturates-induced NAS is not clear, but it is likely similar to that described in the section of this review dedicated to BZDs, thus involving GABA neurotransmission. [197] Standard treatments for the management of barbiturate-associated NAS are not available. Phenobarbital has been shown to be effective in the management of the syndrome, even if an elevated rate of tolerance was reported.…”

Section: Barbituratesmentioning

confidence: 99%

Neonatal Adaptation Issues After Maternal Exposure to Prescription Drugs: Withdrawal Syndromes and Residual Pharmacological Effects

et al. 2016

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Exposure to drugs during pregnancy has the potential to harm offspring. Teratogenic effects are the most feared adverse outcomes in newborns; however, a wide spectrum of less known, usually reversible and often acute, neonatal adverse events can also occur due to drug intake by mothers during pregnancy, particularly in close proximity to delivery. This narrative review is aimed at the description of drugs and drug classes for which licit maternal use in the predelivery period has been associated with neonatal non-teratogenic disorders. For each drug class, epidemiology, clinical features, biological mechanism and management of these adverse reactions have been discussed in detail. Although these adverse reactions have been described mainly for substances used illicitly for recreational purposes, several prescription drugs have also been involved; these include mainly psychotropic medications such as opioids, antidepressants, antiepileptics and antipsychotics. These effects can be partly explained by withdrawal syndromes (defined also as 'neonatal abstinence syndrome') caused by the delivery-related discontinuation of the drug disposition from the mother to the fetus, with symptoms that may include feeding disorders, tremors, irritability, hypotonia/hypertonia, vomiting and persistent crying, occurring a few hours to 1 month after delivery. Otherwise, neonatal neurological and behavioral effects can also be caused by a residual pharmacological effect due to an accumulation of the drug in the blood and tissues of the newborn, with various symptoms related to the toxic effects of the specific drug class, usually developing a few hours after birth. With few exceptions, validated protocols for the assessment and management of withdrawal or residual pharmacological effects of these drugs in neonates are often lacking or incomplete. Spontaneous reporting of these adverse reactions seems limited, although it might represent a useful tool for improving our knowledge about drug-induced neonatal syndromes.

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“…However, what has become apparent is that in some cases this switch over from one medication to the other, particularly from phenobarbital to imepitoin, is taking place without consideration of what would constitute an appropriate withdrawal period. The development of physical dependence is a recognised feature when using phenobarbital (and other barbiturates) (Tanaka and others 1991, Bidlack and Morris 2009). While there will always be situations in which this switch has to be made quickly, particularly in dogs with severe and life‐threatening adverse effects, if the phenobarbital therapy has to be stopped then, wherever possible, it should be gradually tapered off over a period of weeks to months.…”

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confidence: 99%

“…While there will always be situations in which this switch has to be made quickly, particularly in dogs with severe and life‐threatening adverse effects, if the phenobarbital therapy has to be stopped then, wherever possible, it should be gradually tapered off over a period of weeks to months. The clinical manifestations of an abrupt termination of phenobarbital therapy (also referred to as ‘abstinence syndrome’) are characterised by central nervous system hyperexcitability and include motor, autonomic and behavioural changes and in some cases may even include withdrawal seizures (Gay and others 1983, Bidlack and Morris 2009). These withdrawal effects may appear as early as 12 to 24 hours after cessation of phenobarbital therapy and can continue for up to 12 days.…”

mentioning

confidence: 99%