Postictal serum levels of antiepileptic drugs for detection of noncompliance
Specht U, Elsner H, May TW, Schimichowski B and Thorbecke R;
Commented by , 21 Nov 2003
Background
Inadequate adherence to the prescribed drug regimen (noncompliance) occurs in one third to one half of patients with epilepsy (1,2,3), but the extent to which this affects seizure control has not been established.
Aim
To assess how often breakthrough seizures are associated with an otherwise unexplained drop in anticonvulsant blood levels (taken as a measure of noncompliance).
Methods
Young adults with epilepsy were asked to have their serum anticonvulsant drug levels checked within 12 hours of having a seizure. These levels were compared with the mean value of two reference drug levels obtained in the same patient on the same therapeutic regimen (if the two reference levels were highly divergent, the highest was used).
Seizures were considered associated with noncompliance if the postictal drug level had dropped by more than 50% compared with the reference level (after excluding other possible reasons for the drug level change).
Results
A total of 52 patients aged 13-33 years (23 with idiopathic generalized epilepsy, 24 with cryptogenic or symptomatic epilepsy, and 5 with other types of epilepsy) provided 61 postictal samples, for a total of 88 drug determinations. Most patients received carbamazepine, valproate or lamotrigine.
A drop in serum levels of more than 50% was observed in 44% of the seizures. Fourteen of the 88 determinations yielded drug levels below the limit of detection.
Noncompliance as assessed by postictal drug levels was more common in patients with a history of variable baseline drug levels, and in those receiving combination drug therapy.
Discussion
This study suggests that breakthrough seizures are caused by noncompliance in a high proportion of patients. Although others investigators have described low anticonvulsant blood levels after a seizure (4,5,6), this study is original because an attempt was made to determine whether these low levels resulted from noncompliance.
The reported high rate of noncompliance is comparable to that observed in a study that used an electronic device to monitor openings of the patient’s pill box (7). In that study, 11 of 19 seizures (58%) in 55 patients were related to a missed dose.
One limitation of the current work is that it provides inadequate information on the characteristics of the patients. In particular, their educational level, their seizure frequency, and the duration of observation are not specified. Therefore, it is unclear whether this population would be representative of patients that we see in daily practice. Additionally, it would have been of interest to have a control group to determine how frequently a random blood sample (not taken in association with a seizure) would have led to classify a patient as noncompliant.
One practical message that seems to emerge is that a single postictal blood sample can be a simple method for detecting noncompliance, provided that adequate reference drug levels are available from that patient. It should be realized, however, there may be other causes for fluctuating blood levels (especially for drugs with a short half-life). Therefore, the laboratory result must be interpreted within the context of other available information.
References
1. Bryant SG, Ereshefsky L. Determinants of compliance in epileptic outpatients. Drug Intell Clin Pharm 1981; 16:572-7
2. Kyngas H. Compliance with health regimens of adolescents with epilepsy. Seizure 20000; 9:598-604
3. Cramer JA, Mattson RH, Prevey ML et al. How often is medication taken as prescribed? A novel assessment technique. JAMA 1989 ; 261 :3273-7
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4. McGlone R, Pritty P. Measuring anticonvulsant levels in the accident and emergency department. Arch Emerg Med 1986; 3:141-3
5. Krumholz A, Grufferman S, Orr St, Stern BJ. Seizures and seizure care in an emergency department. Epilepsia 1989 1989; 30:175-81
6. Irving P, Dahma AA, Srinavasan A, Greenwood D. An audit of admissions of patients with epilepsy to a district general hospital. Seizure 1999; 8:1666-9
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7. Cramer JA, Mattson RH Compliance with antiepileptic drug therapy. In: Levy RH, Mattson RH, Meldrum BS, eds, Antiepileptic Drugs, 4th ed, New York, Raven Press, 1995: 149-159
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