Psychiatric symptomatology, scholastics, and phenytoin.

Phenytoin is a commonly used antiepileptic medication because of its easy accessibility as well as affordability. However, scientific literature shows various types of side effects of phenytoin. We report a patient who was showing toxicity symptoms in the form of mood, behavior and cognitive symptoms along with scholastic problems and personality change on long term treatment with phenytoin. The patient's serum phenytoin was found to be quite high (>32.8 ng/ml).The symptoms were attributed to phenytoin toxicity which responded within twelve weeks by reducing the dose of phenytoin (with resultant fall in levels of serum phenytoin) and the addition of folic acid. While the mood and behavior symptoms recovered early, the cognitive symptoms responded slowly showing 80% -90 % improvement over a period of fifteen weeks.

INTRODUCTION

We report a case illustrating how the hazardous cognitive effects of chronic phenytoin administration (in the form of scholastic deterioration) transformed into mood and behavioral changes and even suicidality.

CASE REPORT

A 28 year unmarried Hindu male of middle socioeconomic status presented with complaints of initial scholastic deterioration, social withdrawal, aggressive and violent behavior, slowness, forgetfulness, anxiety, decreased confidence, sadness, and occasional suspiciousness for the last 5 years and suicidal gestures since 18 months. There was history of epilepsy since last 13 years for which he was receiving 300 mg/d of phenytoin. A provisional diagnosis of mood disorder with epilepsy was kept. However, on investigating, serum phenytoin level was found to be highly elevated at 32.8 mcg/ml (normal range=10-20 mcg/ml), while serum folic acid level was below the normal range 5.23 ng/ml (normal >5.38 ng/ml). Thus, diagnosis was revised and the patient was classified as a case of phenytoin toxicity. Keeping in mind that cognitive impairment due to phenytoin resolves on drug withdrawal,[1] phenytoin was tapered off (50 mg/ every sixth day) from 300 mg/day and folic acid 5 mg/d was supplemented. The symptom course was closely monitored and supportive psychotherapy instituted during hospitalization; the patient received no other psychopharmacological agents. Within the 2 weeks hospitalization phase, subject showed global improvement of 20% in behavioral symptoms and mood but there was little improvement in his cognitive symptoms. By third follow-up at 11 weeks, cognitive symptoms showed improvement as well and global improvement of 60-70% was reported- in line with another study.[2] However, an episode of tonic-clonic seizure occurred at this time, and considering the phenytoin toxicity, the patient was put on Divalproex 500 mg/d. No seizures occurred till the 15th week during fourth follow up and the family reported near complete resolution also of his neuropsychiatric symptoms.

DISCUSSION

Origin of the depressive symptoms and aggressive and violent behaviour is debatable. While their resolution consequent to tapering off phenytoin and folic acid supplementation implicates phenytoin induced decreased folic acid levels[3] and its subsequent correction, it could also be visualized as a secondary reaction to the scholastic handicap due to cognitive deficit. This subject had obtained 53% and 64% in high-school and intermediate examinations, respectively, but thereon could not qualify in competitive examinations for next 4 years and finally gave up switching to take up a BSc (Bachelor of Science) course. In this, feeling unable to cope with the studies, he did not appear in examinations at the end of the session and switched to undertake the less rigorous BA (Bachelor of Arts) course as a desperate last resort. However, he could not pass that also in the first attempt, only clearing in the second but with less than 50% marks.

At the time of his presenting to us, he had further switched his career stream, being enrolled in Diploma in Tourism and was brought to us for very irregular attendance, not appearing for his examinations and not showing interest in current activities and studies. The scholastic deterioration was manifest in his performance decreasing, which invoked certain psychological sequelae which affected not only his vocational domains, but interpersonal and social domains as well. Initially, the decreased performance produced anxiety which served to enhance performance driven activity. However, when the subject felt that even his enhanced efforts over a considerable period of time did not produce improved cognitive performances, this mismatch led to irritation, depression, worthlessness, hopelessness, and a sense of doom which even led to his showing or attempting suicidal behaviour at times. This mismatch conflict also reflected as changes in his interpersonal behavior. Due to the scholastic deterioration, the subject, not only had to compromise much in life, but also faced critical comments and ridicule from family and others which consequently led to violent outbursts towards the family and hostility towards others at times leading to a vicious cycle. Such a hypothesis may be in place as two bouts of depression reported during last one and half years lasted for one and one and half months, respectively, and resolved spontaneously without any intervention suggesting it to be arising from the vicious cycle.

The diagnosis of phenytoin intoxication was not an easy one to make in our patient as nystagmus and ataxia were absent among the mood, behavior, and cognitive alterations. Phenytoin intoxication should be considered when any unusual neurological or behavioral disturbance occurs in a patient receiving the drug. The estimation of the serum phenytoin concentration is invaluable in such a situation.[4-6] It has a long mean half life of 40 h[7] and is very cheap compared to its competitors making it highly acceptable. However, the fact that phenytoin might be more deleterious to higher cognitive functions than carbamazepine or sodium valproate[28] is still commonly ignored and the drug widely used without exercising the necessary precautions entailed in its administration as this case depicts with serum phenytoin levels never having been estimated before hospitalization. Importantly, these harmful cognitive effects, if undetected, may roll on to pronounced psychological sequelae like depression, hopelessness, and even suicide.

The case illustrates how scholastic performance in students/scholars is extremely vital for them and any scholastic deterioration runs the risk of hazardous ramifications and implications. Thus, short-term or long-term use of drugs affecting cognition must be peppered with caution especially in select groups like scholars, students, executive, and the like.