Multiple anti-epileptic drug use in children with epilepsy in Mulago hospital, Uganda: a cross sectional study
Rita AtugonzaAngelina Kakooza‐MwesigeSamden D. LhatooMark KaddumukasaLevicatus MugenyiMartha SajatovicElly KatabiraRichard Idro
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Seizures in up to one third of children with epilepsy may not be controlled by the first anti-epileptic drug (AED). In this study, we describe multiple AED usage in children attending a referral clinic in Uganda, the factors associated with multiple AED use and seizure control in affected patients. One hundred thirty nine patients attending Mulago hospital paediatric neurology clinic with epilepsy and who had been on AEDs for ≥6 months were consecutively enrolled from July to December 2013 to reach the calculated sample size. With consent, the history and physical examination were repeated and the neurophysiologic and imaging features obtained from records. Venous blood was also drawn to determine AED drug levels. We determined the proportion of children on multiple AEDs and performed regression analyses to determine factors independently associated with multiple AED use. Forty five out of 139 (32.4 %) children; 46.7 % female, median age 6 (IQR = 3–9) years were on multiple AEDs. The most common combination was sodium valproate and carbamazepine. We found that 59.7 % of children had sub-therapeutic drug levels including 42.2 % of those on multi-therapy. Sub-optimal seizure control (adjusted odds ratio [ORa] 3.93, 95 % CI 1.66–9.31, p = 0.002) and presence of focal neurological deficits (ORa 3.86, 95 % CI 1.31–11.48, p = 0.014) were independently associated with multiple AED use but not age of seizure onset, duration of epilepsy symptoms, seizure type or history of status epilepticus. One third of children with epilepsy in Mulago receive multiple AEDs. Multiple AED use is most frequent in symptomatic focal epilepsies but doses are frequently sub-optimal. There is urgent need to improve clinical monitoring in our patients.Keywords:
Cross-sectional study
Eighteen patients with rapid cycling bipolar affective disorder were recruited for an open trial of carbamazepine. Of these patients all but 2 had been resistant to lithium prophylaxis. Twelve of the patients were able to complete at least 6 months on carbamazepine. Of these 12 patients, 2 had a complete remission of their affective disorders on carbamazepine alone, 2 completely responded to combined lithium and carbamazepine treatment, 3 had a slight beneficial effect from the drug, and for the other 5 patients carbamazepine was of no therapeutic benefit. This suggests that, while carbamazepine is effective for some rapid cycling patients, for the majority alternative treatment strategies are still required.
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Stevens-Johnson syndrome (SJS) is a rare but life-threatening skin reaction disease and carbamazepine is one of its most common causes. We report a case of SJS secondary to carbamazepine in a patient with previous pruritus due to carbamazepine which was given for treatment of trigeminal neuralgia. We would like to caution all providers that carbamazepine readministration should be avoided in the patient with a previous history of SJS or adverse skin reaction. In addition, we strongly recommend gradual titration when initiating treatment with carbamazepine.
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Denzimol, a new anticonvulsant drug, is currently undergoing clinical evaluation. In this paper we report its use in six patients who were also taking carbamazepine and two patients taking phenytoin. There was a striking elevation of serum carbamazepine, carbamazepine-10, 11 epoxide and phenytoin concentrations in all patients on the addition of denzimol therapy. The interaction with carbamazepine is greater in severity than any other reported to date and denzimol9s interaction with both carbamazepine and phenytoin is likely to prove of major clinical significance.
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OBJECTIVE:To evaluate the clinical use of carbamazepine.METHODS:The monitoring results of blood concentration of carbamazepine in 189 patients with epilepsy after treatment with carbamazepine were analyzed retrospectively. RESULTS:As for blood concentration of carbamazepine,4 mg·L~(-1) appeared in 32 FD cases,and 20(62.5%) of the them were effective, 12 mg·L~(-1) was found in 2 FD cases,and both(100%) of the two cases were effective,and 4～12 mg·L was found in 15,5 cases,of whom,114(73.5%) were effective.When comparing the effective rate between the patients receiving carbamazepine alone and those treated with carbamazepine in combination with other antiepileptic drugs,all P 0.05, therefore,significant difference between the two groups in the total effective rate could not be considered.CONCLUSION: The blood concentration of carbamazepine showed great individual difference.Individualized dosage regimen should be made based on the monitoring on the blood concentration of carbamazepine and its clinical therapeutic effect.
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The treatment efficiency was compared to blood carbamazepine++ levels in patients with trigeminal neuralgia which were treated with the drug over a long period. The parameters displayed a good (r = 0.70) correlation that resulted in a tendency to increase treatment effect with carbamazepine++ plasma concentration increase. The treatment proved most efficient and side effect-free in a concentration range of 5 to 10 micrograms/ml. The data on blood carbamazepine++ concentrations may be helpful in designing a controlled course of treatment.
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Carbamazepine is a suitable substitute for phenobarbital, primidone, and phenytoin, alone or in combination, when used in the treatment of generalized tonic-clonic or partial epilepsy. Seventy-five percent of 19 patients successfully transferred to carbamazepine and clinically their seizures were at least as well controlled during 18 months of observation. Carbamazepine, alone, is not a satisfactory substitute for drug combinations used in the treatment of compound epilepsy. Fifty percent of 18 patients were successfully transferred to carbamazepine but few of them were significantly improved during the 24 month follow-up. The gradual replacement of standard anticonvulsants with carbamazepine can be accomplished without seizure exacerbation, often with improved control and patient satisfaction. Unfavorable reactions usually are brief, provided serum levels are established between 5 and 12 micrograms/ml.
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A battery of psychometric tests was administered to 85 patients with epilepsy, of whom 26 were untreated, 40 received carbamazepine monotherapy and 19 took carbamazepine with another anticonvulsant. Carbamazepine alone had little effect on performance, but carbamazepine polypharmacy produced significant impairment. Increasing concentrations of carbamazepine (four tests) and its active metabolite, carbamazepine 10,11 epoxide (seven tests), correlated with decreasing performance in the monotherapy patients.
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Epilepsy syndromes
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Introduction Despite neurological presentations accounting for around 15% of all hospital admissions, data on inpatient referrals to neurology is limited. 1,2 Early intervention from a neurologist can improve clinical outcomes and reduce readmissions.3 Therefore, it is important that referral processes are reviewed and developed to improve clinical effectiveness Methods The study aimed to identify reasons for referral to neurology in addition to outcomes of the referral. 50 consecutive referral forms from February 1st 2019 were reviewed to collect data. Results Most common reason for referral was for advice on management of a long-term neurological condition (n=15, 30%), followed by new onset seizures (n=11, 22%) and focal neurological deficits (n=11, 22%). Referrals commonly resulted in further imaging (n=17, 34%) and investigations (n=17, 34%), followed by medication advice (n=16, 32%). Discussion Neurology services are used for both input on acute management of a new neurological presentation and advice on management on chronic neurological conditions. Seizure management is common in both categories. Referrals commonly result in requests for further investigations, however, it is perhaps less commonly documented when further tests are advised against. Overall, the neurology referral form could be adapted to reflect the above conclusions, to increase efficiency of the service. Loredana.kent@nhs.net
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Clinical neurology
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