This survey of Zambian pharmacies identified limited and unpredictable AED access in two large Zambian provinces and supports clinician concerns and patient complaints that AED access has recently worsened. Similar problems have been reported for other essential medications, indicating a stark gap between policy and practice in developing regions.11
Historically, phenobarbitone has been the AED most commonly used and available in Zambia because of its low cost.12
Phenobarbitone is, however, a scheduled drug based on the United Nations Convention on Psychotropic Substances (1971).13
Recent efforts through the WHO Expert Committee on Drug Dependence have emphasized to authorities in low- and middle-income countries the need for proper management of scheduled medications.10,14
These well-intended efforts may play a role in the recent enforcement activities of the Zambian PRA that have had the unintended consequence of decreasing AED access. The selection of medications for inclusion in the 1971 schedule IV drug list was based on the chemical structure of the agent without consideration of the actual abuse potential in human populations. Personal communications with epilepsy-care providers in other low- and middle-income countries suggest that Zambia is probably not alone in being affected by new regulatory activities that are causing a shortage of affordable AEDs, with phenobarbitone being especially unavailable (J.W.A.S. Sander, personal communication; C.A. Schwartzmann, personal communication).
Obviously, the need to balance drug availability with proper regulatory oversight is a difficult one. The lack of trained pharmacists in our survey suggests that the human resources for appropriate management of prescription drugs are limited. Recent health-services publications have suggested that low- and middle-income countries may be able to use pharmacy services to enhance public health,15
but where no expertise are available, this will not be possible. When AEDs are only available through private pharmacies, the cost is likely prohibitive for many PWE, because the average monthly income in Zambia is $125,16
with median household incomes being < $2/day, and PWE as a group have a particularly low socioeconomic status.17
In resource-poor countries like Zambia, work undertaken by physicians in developed countries is often taken over by other healthcare personnel, such as clinical officers. One might consider the need to develop formal training for pharmacy dispensers in a setting where adequate numbers of fully trained pharmacists are not readily available.
Theoretically, epilepsy care can be cost-effective in low- and middle-income countries. Chisholm,18
among others, has concluded that the large treatment gap in resource-poor countries can be reduced considerably by scaling up the routine availability of low-cost AEDs. However, this otherwise reasonable assertion does not include the potential additional costs imposed by regulatory actions on phenobarbitone as a scheduled medication.
Many additional drug-access and quality issues need to be addressed urgently. The lack of safe and effective outpatient AED therapy for neonates and infants given the absence of pediatric syrups is especially concerning. In 2007, the Expert Committee on Essential Medicines added a number of pediatric dosage forms of AEDs to the list,19,20
and there have been recent calls for better AED access for children.21
Nevertheless, pediatric AED formulations are not presently available in Zambia, and the probability of inconsistent dosing of AEDs and potential toxicity looms large for clinicians and parents trying to divide adult-size tablets for pediatric populations, especially with AEDs that have a narrow therapeutic margin. Of course, encouraging preparation of these syrups by untrained pharmacy staff could be disastrous. Even when apparent dosing is correct, problems may remain. Recent data from Rwanda indicated that routine storage facilities for antihypertensive medications in low-income tropical settings may result in 20% of these medications having substandard content by the time of distribution.22
We have been unable to find any data on the shelf life of common AEDs when they are stored outside of the tight specifications recommended by the drug manufacturers.
This study did not identify any macro-level determinants of AED availability or cost based on urbanicity or ownership. A post hoc power calculation for the availability analysis indicates that this analysis had 90% power to detect a 2.5-fold difference in availability. Because government pharmacies provide AEDs for free, the cost analysis was limited to private pharmacies (N = 42), and hence, the power was substantially lower for this analysis. Despite these findings, the indirect costs of accessing medications, in terms of transport costs and time, are almost certainly higher for rural PWE.
This work has several strengths and limitations. We were able to complement the quantitative survey data with qualitative interviews, but only a subset of pharmacies was included in the interview sample. To protect the identity of study participants from unregistered pharmacies, the PRA registration status variable was dropped from the dataset, and data were deidentified; therefore, we could not formally assess whether AED availability or cost was related to this characteristic, but unregistered pharmacies comprised < 10% of pharmacies identified. It might be sufficient for only a core group of pharmacies to carry AEDs, if such pharmacies were geographically distributed and they could provide AEDs consistently. However, based on our findings, AED availability, even within a given pharmacy, is inconsistent (note the number of pharmacies that did not have a given AED on the date of the survey but report carrying the medications at times). A repeated survey design with data on spacial distribution would be needed to clarify whether there could be a core of pharmacies identified that could reliably provide AEDs for the population. We report findings from only one African country, and within that country, we studied two provinces. However, the provinces selected were two of the three most populated, and we have some anecdotal information through personal communications with epilepsy-care providers working in other low-income regions that indicate that the problem of increasing drug regulation causing declining AED availability may be widespread.
In catchment areas with dedicated epilepsy clinics, it may be possible for local staff to assure availability of AEDs to their immediate clinic population through dedicated purchase and persistent requests to government pharmacy staff to assure timely stocking. However, large-scale, community-based efforts to encourage PWE to come “out of the shadows” must only be undertaken when adequate access to AEDs can be assured for those PWE convinced to seek care. Collaborative and intra-programmatic discussions are urgently needed within local and international governmental bodies to examine the complex realities of AED drug supplies in low-income countries and to develop processes for more affordable and accessible AED options. Otherwise, epilepsy will, indeed, remain in the shadows.