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Donepezil was withdrawn, and no other drug treatment was given. Blood analysis was normal, and a computerized tomographic (CT) scan showed a mild degree of cortical atrophy with no structural lesions. His only other medication was aspirin 100 mg/day. Ī patient with mild Alzheimer’s disease taking donepezil, 5 mg/day for 2 weeks and then 10 mg/day for 23 days, was admitted with convulsions.Baclofen should probably be considered at an early stage, as it might be the most effective anticonvulsant in such cases.Ĭonvulsions have been reported during treatment with donepezil. The first priority in such a case is to rule out other causes, such as infections, electrolyte disturbances, and intracranial pathology, and to prevent secondary brain damage due to prolonged convulsions.

In conclusion, baclofen withdrawal should be suspected if postnatal convulsions occur after intrauterine exposure. The half-life of baclofen in adults is 3–6 hours, and adults usually become symptomatic 24–72 hours after baclofen is reduced or withdrawn. On the other hand, the authors stated that the mother had noted some abnormal movements starting on the second day postpartum, which might have represented the first signs of withdrawal. This is of course speculative nothing is known about baclofen pharmacokinetics in neonates.

In discussing the possible mechanisms of the delayed onset of convulsions the authors assumed that a secondary increase in baclofen serum concentration due to redistribution might have prevented earlier onset of the withdrawal symptoms. An MRI scan of the brain on day 17 suggested a hypoxic ischemic insult in the perinatal period, which was considered to have been secondary to convulsions.Īs convincingly presented by the authors, baclofen withdrawal was the most likely explanation for the convulsions. The baclofen was then slowly withdrawn over 2 weeks. The baby was given baclofen 0.25 mg/kg qds and 30 minutes after the first dose the convulsions stopped. At that time baclofen withdrawal was suspected, as the paraplegic mother had been taking baclofen 20 mg tds throughout pregnancy. Electroencephalography 4 days later showed prolonged episodes of epileptic activity. A variety of investigations all gave negative results.

Ī 7-day-old baby was admitted to hospital with generalized convulsions, which did not respond to phenobarbital, phenytoin, clonazepam, lidocaine, or pyridoxine.

These findings provide evidence that the behaviors exhibited by animals must be carefully evaluated to determine if they represent premonitory signs of a convulsion or unrelated pharmacological responses of a test article.Ĭonvulsions have been attributed to withdrawal of baclofen after in utero exposure. Body temperature may be altered in the absence and presence of convulsions in animals, as well as by the effects that depend on the dose schedule of the treatment drug (see Tor-Agbidye et al., 2001). However, note that temperature regulation is an important factor that may influence the susceptibility of animals to convulsions, as mentioned above and elsewhere. For example, behaviors such as tremors and shaking may be due to drug-induced hypothermia. Although these signs and convulsions may be related, these signs may represent pharmacological effects produced by a drug. Convulsions in animals may be preceded by premonitory signs that include head and body tremors, incoordination, and ataxia (see Bassett et al., 2014 Smythe et al., 1988). Death may also occur in animals that exhibit convulsions but do not develop status epilepticus. In cases in which convulsions occur continuously, animals may develop status epilepticus, a condition that may result in the occurrence of brain lesions and death ( Albala et al., 1984 Cavalheiro et al., 1987 McKhann et al., 2003 McLin and Steward, 2006). Delatte, in Advanced Issue Resolution in Safety Pharmacology, 2019 Behavioral ObservationsĬonvulsions may be manifested behaviorally in animals via the exhibition of a variety of clinical signs that include (but are not limited to) facial or forelimb clonus, tonic posturing, tonic–clonic posturing, and myoclonic jerks.