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Interaction between phenytoin and fluoxetine
Seizure 1994; 3:151-152
CASE REPORTS
Interaction between phenytoin and fluoxetine J. DARLEY
The selective serotonin-reuptake inhibitors (SSRI's) are seen as potentially beneficial in patients who are depressed and who are also epileptic. This is largely because of the increased risk of seizures in patients taking tricyclic antidepressants, estimated to occur in 0.5-1% of patients. Leander l presents data to suggest that fluoxetine, through its selective inhibition of serotonergic reuptake, may have beneficial advantages in the treatment of depressed patients with epilepsy and m a y also enhance the seizure control of prototypical anticonvulsants in the treatment of epilepsy. It is also thought that the SSRI's appear to be free of most of the significant d r u g - d r u g interactions that m a y occur with the earlier antidepressants 2. However, the data sheets of two SSRI drugs recommend careful monitoring in patients with controlled epilepsy, while two others specifically mention an interaction with phenytoin. There has also been a recent report 3 that the addition of fiuoxetine to a stable dose of phenytoin resulted in phenytoin toxicity in two women. I would like to report another case where the addition of fluoxetine resulted in phenytoin toxicity.
CASE REPORT
A 33-year-old male was referred to the neuropsychiatric clinic by his General Practitioner with a 6 week history of low mood and psychomotor retardation. There was a history of epilepsy for nearly 20 years which had been treated with various medication, but for some years had been treated with phenytoin. The dose of phenytoin necessary to control the seizures, which were generalized tonic-clonic in nature, was high and tended to give blood levels above the reference range although the patient did not experience toxic effects. Any 1059-1311/94/020151+02 $08.00/0
reduction, even by a small increment, resulted in a return of his seizures. There was also a history of an episode of psychotic depression 7 years previously necessitating admission to psychiatric hospital for treatment, although the patient had not been taking antidepressants for some time. At presentation to the clinic he was complaining of feeling down with no obvious precipitating factors. He had been unable to work for several weeks and had believed that people at work may have been talking about him. His concentration was poor and his energy levels were not as good as usual. His sleep had been affected with disturbed sleep and early morning wakening and there had been some loss of weight. His drug treatment at the time was phenytoin 425 mg daily. Mental state examination revealed the patient to be appropriately dressed but somewhat withdrawn with a degree of psychomotor retardation. Speech was low in volume and rate. Mood was low both subjectively and objectively. He described morbid depressive thoughts although these did not reach delusional proportions and he denied any suicidal ideation. In terms of physical symptoms, he denied any symptoms related to phenytoin toxicity and physical examination was normal. He was started on treatment with fluoxetine, 20mg daily, and reviewed at 1, 2 and 3 months. Although there was some improvement in mood, clinically, this was not total, and the patient felt that he was not back to his normal self. The dose of fluoxetine was increased to 40 mg daily and he was reviewed at 4 months. There was again a slight improvement but this was not complete so the drug regimen was continued. At 6 months, the patient had developed falls, unsteadiness and blurred vision, consistent with phenytoin toxicity and a serum level at this time revealed a phenytoin level of (~ 1994 W.B. SaundersCompany Ltd
J.
152
28.5 mg/1 (recommended therapeutic range 7 20 mg/1). His phenytoin dosage was therefore reduced to 400mg daily but his serum level remained high at 33.3mg/1 with continuing signs of toxicity. With a larger reduction in the dosage of phenytoin his seizures recurred and it was decided to add an additional anticonvulsant to try and achieve better control. Although the use of SSRI's does represent an advance in the management of depression in those at risk from epileptic seizures compared with many other antidepressant compounds which lower the threshold for seizures, drug interactions between anticonvulsants and the SSRI's must be borne in mind.
Darley
REFERENCES 1. Leander, J.D. Fluoxetine, a selective serotonin-uptake inhibitor, enhances the anticonvulsant effects of phenytoin, carbamaz~,pine, and ameltolide (LY201116). Epilepsia 1992; 33:573 576. 2. Boyer, W.F. and Feighner J.P. Perspectives in Psychiatry, Volume 1. Selective Serotonin Re-uptake Inhibitors, 1991, Wiley, England. 3. Jalil, P. Toxic reaction following the combined administration of fluoxetine and phenytoin: two case reports.
Journal of Neur~#c~y, Neurosurgery and Psychiatry 1992; 55: 412-413.
CASE REPORTS
Interaction between phenytoin and fluoxetine J. DARLEY
The selective serotonin-reuptake inhibitors (SSRI's) are seen as potentially beneficial in patients who are depressed and who are also epileptic. This is largely because of the increased risk of seizures in patients taking tricyclic antidepressants, estimated to occur in 0.5-1% of patients. Leander l presents data to suggest that fluoxetine, through its selective inhibition of serotonergic reuptake, may have beneficial advantages in the treatment of depressed patients with epilepsy and m a y also enhance the seizure control of prototypical anticonvulsants in the treatment of epilepsy. It is also thought that the SSRI's appear to be free of most of the significant d r u g - d r u g interactions that m a y occur with the earlier antidepressants 2. However, the data sheets of two SSRI drugs recommend careful monitoring in patients with controlled epilepsy, while two others specifically mention an interaction with phenytoin. There has also been a recent report 3 that the addition of fiuoxetine to a stable dose of phenytoin resulted in phenytoin toxicity in two women. I would like to report another case where the addition of fluoxetine resulted in phenytoin toxicity.
CASE REPORT
A 33-year-old male was referred to the neuropsychiatric clinic by his General Practitioner with a 6 week history of low mood and psychomotor retardation. There was a history of epilepsy for nearly 20 years which had been treated with various medication, but for some years had been treated with phenytoin. The dose of phenytoin necessary to control the seizures, which were generalized tonic-clonic in nature, was high and tended to give blood levels above the reference range although the patient did not experience toxic effects. Any 1059-1311/94/020151+02 $08.00/0
reduction, even by a small increment, resulted in a return of his seizures. There was also a history of an episode of psychotic depression 7 years previously necessitating admission to psychiatric hospital for treatment, although the patient had not been taking antidepressants for some time. At presentation to the clinic he was complaining of feeling down with no obvious precipitating factors. He had been unable to work for several weeks and had believed that people at work may have been talking about him. His concentration was poor and his energy levels were not as good as usual. His sleep had been affected with disturbed sleep and early morning wakening and there had been some loss of weight. His drug treatment at the time was phenytoin 425 mg daily. Mental state examination revealed the patient to be appropriately dressed but somewhat withdrawn with a degree of psychomotor retardation. Speech was low in volume and rate. Mood was low both subjectively and objectively. He described morbid depressive thoughts although these did not reach delusional proportions and he denied any suicidal ideation. In terms of physical symptoms, he denied any symptoms related to phenytoin toxicity and physical examination was normal. He was started on treatment with fluoxetine, 20mg daily, and reviewed at 1, 2 and 3 months. Although there was some improvement in mood, clinically, this was not total, and the patient felt that he was not back to his normal self. The dose of fluoxetine was increased to 40 mg daily and he was reviewed at 4 months. There was again a slight improvement but this was not complete so the drug regimen was continued. At 6 months, the patient had developed falls, unsteadiness and blurred vision, consistent with phenytoin toxicity and a serum level at this time revealed a phenytoin level of (~ 1994 W.B. SaundersCompany Ltd
J.
152
28.5 mg/1 (recommended therapeutic range 7 20 mg/1). His phenytoin dosage was therefore reduced to 400mg daily but his serum level remained high at 33.3mg/1 with continuing signs of toxicity. With a larger reduction in the dosage of phenytoin his seizures recurred and it was decided to add an additional anticonvulsant to try and achieve better control. Although the use of SSRI's does represent an advance in the management of depression in those at risk from epileptic seizures compared with many other antidepressant compounds which lower the threshold for seizures, drug interactions between anticonvulsants and the SSRI's must be borne in mind.
Darley
REFERENCES 1. Leander, J.D. Fluoxetine, a selective serotonin-uptake inhibitor, enhances the anticonvulsant effects of phenytoin, carbamaz~,pine, and ameltolide (LY201116). Epilepsia 1992; 33:573 576. 2. Boyer, W.F. and Feighner J.P. Perspectives in Psychiatry, Volume 1. Selective Serotonin Re-uptake Inhibitors, 1991, Wiley, England. 3. Jalil, P. Toxic reaction following the combined administration of fluoxetine and phenytoin: two case reports.
Journal of Neur~#c~y, Neurosurgery and Psychiatry 1992; 55: 412-413.