Phenytoin, folic acid and gingival enlargement: Breaking myths

BACKGROUND: Epilepsy is described as a chronic neurological disorder characterized by recurrent seizures of cerebral origin, presenting with episodes of sensory, motor or autonomic phenomenon with or, without loss of consciousness. A recent meta-analysis of published and unpublished studies puts an overall prevalence rate of epilepsy in India at 5.59 per 1,000 populations. There have been studies that report clinical benefits of the use of folic acid as an adjuvant to the anti-epileptic therapy in the prevention of anti-epileptic drug induced gingival enlargement. However, studies conducted in the past have also reported precipitation of epileptic attacks in patients on folic acid adjuvant therapy due to fall in sera levels of phenytoin due to drug interactions. The study was planned to investigate the association of phenytoin induced gingival enlargement and sera levels of folic acid in epileptic patients on phenytoin therapy so as to justify the use of folic acid as a routine adjuvant to the usual anti-epileptic therapy to prevent this inevitable adverse effect without destabilizing the ongoing regimen leading to the precipitation of seizures in an otherwise stable patient (breakthrough seizures). MATERIALS AND METHODS: A total of 100 patients between the ages 18 and 50 years were clinically diagnosed with epilepsy prior to the start of phenytoin therapy were included based on selection criteria and written informed consents were obtained. Assessment of serum folic acid levels and gingival enlargement was performed prior to the start of and after 1 year of phenytoin therapy. STATISTICAL ANALYSIS USED: The statistical analysis was carried out using t-test and the baseline serum folate levels and the serum folate levels obtained after 1 year of phenytoin therapy were correlated with the respective grades of gingival enlargement using Pearson's coefficient formula. RESULTS: The results of the study confirmed a significant association between low serum folate levels with increasing severity as well as an early onset of phenytoin induced gingival enlargement. CONCLUSIONS: The results of the study suggest a higher incidence of gingival enlargement with an early onset and increased severity in phenytoin treated epileptic patients with a positive correlation with falling serum folic acid levels as the duration of the therapy increases.