Major findings

Phenobarbital, when administered prenatally in a small dose to animals, produced profound, and permanent effects on reproductive function in the offspring. 2 . Preliminary analysis of a unique cohort of adolescents who were exposed to phenobarbital in utero, suggests that long-term effects are also evident in the human. 2 . The precise nature of these effects is currently being determined and will be reported separately. 2 . These effects may be qualitatively and quantitatively different from effects seen in animals because of species difference in the timing or neuroendocrine differentiation. 2 . Of greater importance, however, is the fact that biologic and pharmacologic effects can be seen in the human following exposure to xenobiotics perinatally. 2 . Implications for other pharmacologic agents await further investigation. 2 . The rat model appears to have validity for extrapolation to man. 2 .

Previous studies have suggested that phenobarbital is as effective in monotherapy as phenytoin and carbamazepine. 5 . Several observational studies undertaken in developing countries over the last decade have confirmed its efficacy and safety for the common epilepsies. 5 . 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. 5 . Phenobarbital is still widely used for neonatal and childhood seizures and for drug-resistant convulsive and nonconvulsive status epilepticus. 5 . 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. 5 . 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. 5 . 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. 5 . 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. 5 . Indeed, there were some cognitive gains in the patients possibly due to improved seizure control. 5 . Phenobarbital is still the most cost-effective pharmacologic treatment for epilepsy. 5 . 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. 5 .

Phenobarbital was found to induced CNS-depressing effects as assessed by visual analogue rating scales (VARS) and critical flicker fusion tests (CFF). 3 . These effects could be documented only for up to 9 h after administration. 3 . This suggests that pharmacodynamic tolerance develops rapidly even after a single oral dose of the drug. 3 .

There were no significant differences in IQ (Binet or Bayley Scales) between placebo and phenobarbital groups after eight to 12 months of therapy. 1 . However, detrimental effects of phenobarbital were found in memory, for which serum level influenced scores, and in comprehension, in that length of treatment time affected performance. 1 . Hyperactivity was not seen. 1 . Behavioral changes, reported by parents, were increased fussiness and a characteristic disturbance of sleep. 1 . These changes varied in severity and were classified as transient, dose related, or unacceptable. 1 . After 12 months in the study, most parents could not distinguish between phenobarbital and placebo. 1 . These data suggest that although most toddlers do not have major side effects from phenobarbital therapy when treated for a year, serum levels and length of time on phenobarbital should be kept at a minimum to reduce negative cognitive and behavioral effects. 1 .

In recent years, phenobarbital, as an antiepileptic drug, has become less popular based on adverse events, especially cognitive and behavioural side effects. 4 . Despite the development of better tolerated new generation AEDs, phenobarbital is still widely used particularly in developing countries because of its low cost. 4 . The purpose of this review was to: (i) investigate whether phenobarbital can be safely used as an antiepileptic drug and (ii) determine the questions which need to be addressed in order to comprehensively and adequately evaluate the safety of phenobarbital for the treatment of epilepsy. 4 .

Benefits and Risks

Benefit Summary

Phenobarbital has been shown to be an effective medication for the treatment of epilepsy. 5 . It is particularly effective for neonatal and childhood seizures, and for drug-resistant convulsive and nonconvulsive status epilepticus. 5 . In addition, phenobarbital is more cost-effective than other antiepileptic drugs. 5 .

Risk Summary

Phenobarbital can cause adverse events, such as cognitive and behavioral side effects. 4 . It may also produce profound, and permanent effects on reproductive function in the offspring when administered prenatally. 2 . Additionally, phenobarbital can be associated with a range of congenital defects in exposed infants. 5 .

Comparison between studies

Commonalities between studies

All of these studies focused on the efficacy and safety of phenobarbital. Moreover, all of these studies showed that phenobarbital is still widely used, especially in developing countries. 4 .

Differences between studies

These studies differed in how they investigated the effects of phenobarbital. Some studies used a rat model, which is considered valid for extrapolation to man. 2 . Other studies used human subjects. 3 . In addition, these studies differed in the timing of exposure to phenobarbital. Some studies investigated prenatal or postnatal exposure, while others investigated exposure over longer periods. 2 .

Consistency and contradictions in the findings

These studies suggest that phenobarbital has both efficacy and safety. However, the side effects of phenobarbital can vary depending on individual factors. 1 . Additionally, the side effects of phenobarbital may depend on the dose and duration of treatment. 1 .

Implications for everyday life

Phenobarbital is an effective medication for the treatment of epilepsy, but it’s important to be aware of the risks of side effects. 4 . If you are taking phenobarbital, it is important to take it as directed by your doctor and to consult with your doctor if you experience any side effects. 4 .

Limitations of current research

These studies have limitations, such as small sample sizes. This makes it difficult to generalize the results of these studies to larger populations. 1 . Also, these studies were conducted using different methodologies, which makes it difficult to compare the studies. 4 .

Directions for future research

Larger studies are needed to further investigate the effects of phenobarbital. 1 . These studies should be conducted in different populations and should examine the most common side effects experienced by people taking phenobarbital. 4 .

Conclusion

Phenobarbital is an effective medication for the treatment of epilepsy, particularly in developing countries. 4 . However, phenobarbital can cause adverse events, such as cognitive and behavioral side effects. 4 . Therefore, it is important to take phenobarbital as directed by your doctor and to consult with your doctor if you experience any side effects. 4 .