title: Medication side effects among people with epilepsy taking phenobarbital in Zambia.
abstract: Phenobarbital remains one of the most widely used antiepileptic drugs worldwide, yet there are limited data regarding side effects associated with its use in routine clinical care settings in low-income countries. Available data suggests that phenobarbital is as effective as other first-line drugs for treating tonic-clonic seizures, but side effect reports differ widely between high and low-income settings. A better understanding of phenobarbital side effect profile and severity in low-income settings is warranted given its role in efforts to decrease the epilepsy treatment gap. We used the Liverpool adverse events profile (LEAP) to assess side effects in consecutive patients with epilepsy on phenobarbital seeking care in rural Zambia. Data regarding age, gender, medication dose, and medication adherence were also collected. T-tests and Spearman's correlation coefficient were used to assess predictors of LEAP score and medication adherence. Thirty-five patients receiving a mean dose of 2.1mg/kg/day (SD: 2.78 mg/kg/day) of phenobarbital were assessed. All participants reported at least one side effect in the previous four weeks with a median of 6 symptoms (IQR: 4-8) and a mean side effects score of 28/76 (SD: 5.38). Over half reported sleepiness and dizziness. Memory problems and depression were also common (both 46%). Total LAEP score was not associated with age (p=0.88), gender (p=0.17), or phenobarbital dose (p=0.13). Medication adherence was not associated with side effects total score (p=0.56). Rural Zambian adults taking phenobarbital at doses recommended by the World Health Organization report a significant number of side effects. The most common side effects reported were similar to those reported in high-income countries. The significant burden of phenobarbital-associated side effects in this African cohort is in contrast to data from non-randomized clinical trials in China that reported phenobarbital to be well-tolerated with few side effects. Additional investigations regarding phenobarbital side effects during routine care in low income settings is warranted.
authors.affiliation: Michigan State University, International Neurologic & Psychiatric Epidemiology Program (INPEP), East Lansing, MI, USA; Michigan State University, College of Human Medicine, East Lansing, MI, USA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Elafros
authors.affiliation: Sunnybrook Health Sciences Centre, Department of Medicine, Toronto, Ontario, Canada.
authors.forename: Esther
authors.initials: E
authors.lastname: Bui
authors.affiliation: Chikankata Hospital, Epilepsy Care Team, Mazabuka, Zambia; University of Rochester, Department of Neurology, Epilepsy Division, Rochester, NY, USA; University of Rochester, Department of Public Health, Rochester, NY, USA. Electronic address: gretchen_birbeck@urmc.rochester.edu.
authors.forename: Gretchen L
authors.initials: GL
authors.lastname: Birbeck
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects*; D004827:Epilepsy / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D006801:Humans; D008297:Male; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000453:epidemiology; D010634:Phenobarbital / Q000009:adverse effects*; D018434:Sickness Impact Profile; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D055815:Young Adult; D015024:Zambia / Q000453:epidemiology
chemical_list: D000927:Anticonvulsants; D010634:Phenobarbital
keywords: Adverse effects; Antiepileptic drugs; Low-income setting; Sub-Saharan Africa; Treatment gap; Treatment outcome