Current position of phenobarbital in epilepsy and its future

Abstract

SUMMARYThis article reviews the current position of phenobarbital using articles published since 2000 and speculates on its likely future contribution to epilepsy care. Over the last decade there have been no major double-blind randomized placebo-controlled or comparative trials with phenobarbital. Previous studies have suggested that phenobarbital is as effective in monotherapy as phenytoin and carbamazepine. Several observational studies undertaken in developing countries over the last decade have confirmed its efficacy and safety for the common epilepsies. This was particularly so in the substantial demonstration project undertaken in rural China under the auspices of the World Health Organization in partnership with the International League Against Epilepsy and International Bureau for Epilepsy. Phenobarbital is still widely used for neonatal and childhood seizures and for drug-resistant convulsive and nonconvulsive status epilepticus. Recent data have confirmed in a prospective cohort of women taking phenobarbital as monotherapy that the drug can be associated with a range of congenital defects in exposed infants. Much effort has gone into exploring the apparent contradiction of higher withdrawal rates due to cognitive and behavioral side effects in studies undertaken in developed countries but not in those sited in the developing world. A raft of data over the last 10 years, including a systematic review, showed no important differences between the tolerability of phenobarbital compared to that with other antiepileptic drugs. Finally, cognitive test scores and mood ratings in 136 people with epilepsy receiving phenobarbital for a year were similar to those in 137 age-, sex-, and education-matched controls in a number of Chinese villages. Indeed, there were some cognitive gains in the patients possibly due to improved seizure control. Phenobarbital is still the most cost-effective pharmacologic treatment for epilepsy. All these data predict a healthy future for phenobarbital, particularly in helping to close the treatment gap in low-and middle-income countries during its second century of clinical use.

Drug treatment of epilepsy in adults

“…Phenobarbital has an extremely low potential for misuse. 41 Its use in developed countries has been limited by a comparative trial that showed that phenobarbital and primidone (which is metabolized to phenobarbital) were less well tolerated than phenytoin or carbamazepine. 42 This finding is less relevant for resource poor countries when the only choice is between phenobarbital or no treatment at all.…”

“…The side effects of phenobarbital-mainly sedation, possible mild cognitive impairment, and depression-can be minimized by using the lowest possible effective dose. 41 Thus, phenobarbital is the current drug of choice for large scale, community based programs, particularly in rural and remote areas of developing countries. 41 Despite the availability of phenobarbital for more than 90 years and its modest cost, the treatment gap for epilepsy still exceeds 90% in many developing countries.…”

Effect of Aqueous Extract Withania somnifera on Tolerance to Antiepileptic Effect of Phenobarbitone in Mice

“…Compare to other AEDs greater like hood for PHB to be withdrawn compared with other AEDs possibly due to higher doses and concerns about its toxicity. 3 It is as effective in monotherapy to control seizures as phenytoin and carbamazepine. 4 So therefore need of the drugs that delay in development tolerance, improve cognitive function and reduce epilepsy induced oxidative stress.…”

Phenobarbital loaded microemulsion: development, kinetic release and quality control

“…It is widely used as an antiepileptic drug for it is complete and very effective drug and has advantages such as low cost, broad spectrum of action and ease of use (Dalmora et al, 2010). It is a centenarian drug and is still the best costbenefit pharmacological treatment for epilepsy, especially in developing countries (Brodie, Kwan, 2012).…”