Progress in Immunization Safety Monitoring - Worldwide, 2020-2022.

Effective surveillance of adverse events following immunization (AEFIs) primarily relies on the collaboration of two partners: national regulatory authorities (NRAs) and national expanded programs on immunization (EPIs). In December 2020, the World Health Organization (WHO) Global Advisory Committee for Vaccine Safety recommended a new case-based indicator of national capacity to monitor immunization safety: at least one serious AEFI reported per 1 million total population per year. To achieve this indicator, WHO-affiliated countries and territories (WHO countries) rely upon data generated from functional AEFI surveillance systems. This report describes 2020-2022 global, regional, and national progress in use of the newly introduced immunization safety monitoring indicator and progress on joint AEFI reporting from national EPIs and NRAs. Among WHO countries, 51 (24%) of 214 implemented the new indicator in 2020, 111 (52%) of 214 implemented it in 2021, and 92 (43%) of 215 in 2022. In 2020, 41 (19%) WHO countries reported AEFI data jointly from EPIs and NRAs; this increased to 55 (26%) in 2021 and 57 (27%) in 2022. These findings, resulting in part from the intensified support for COVID-19 vaccination, demonstrate that national AEFI surveillance systems increasingly support the timely use and sharing of case-based immunization safety data, but work is still needed to strengthen global vaccine safety monitoring.

Strengthening therapeutic adherence and pharmacovigilance to antimalarial treatment in Manaus, Brazil: a multicomponent strategy using mHealth.

BACKGROUND: Public health initiatives for improving adherence to primaquine based regimens and enhancing effective pharmacovigilance are needed to support the efforts for malaria elimination in real world conditions. METHODS: A multicomponent patient-oriented strategy using a Smart Safety Surveillance (3S) approach including: (1) educational materials for treatment counselling and identification of warning symptoms of haemolytic anaemia; (2) an mHealth component using Short Message Service (SMS) treatment reminders and (3) development and implementation of follow-up phone surveys three days after treatment completion, using a web-based platform linked to the local information system of malaria. Adherence was measured using the Morisky Medication Adherence Scale. Self-reported events were registered using a structured questionnaire and communicated to the Brazilian Health Regulatory Agency. RESULTS: Educational materials were disseminated to 5594 patients, of whom 1512 voluntarily entered the mHealth component through the local information system; 7323 SMS were sent, and 1062 participants completed a follow-up survey after treatment. The mean age of patients was 37.36 years (SD 13.65), 61.24% were male, 98.54% were infected with. Plasmodium vivax and 95.90% received a short regimen of chloroquine plus primaquine (CQ + PQ 7 days), as per malaria case management guidelines in Brazil. From the 1062 surveyed participants 93.31% were considered adherent to the treatment. Most of the patients (95.20%) reported at least one adverse event. Headache, lack of appetite and nausea/vomiting were the most frequently reported adverse events by 77.31%, 70.90% and 56.78% of the patients respectively. A quarter of the patients reported anxiety or depression symptoms; 57 (5.37%) patients reported 5 to 6 warning symptoms of haemolytic anaemia including jaundice and dark urine in 44 (4.14%). Overall, three patients presenting symptoms of haemolytic anaemia attended a hospital and were diagnosed with G6PD deficiency, and one had haemolysis. All of them recovered. CONCLUSIONS: Under real world conditions, a multicomponent patient-oriented strategy using information and communication technologies allowed health care providers to reinforce treatment adherence and enhance safety surveillance of adverse events associated with regimens using primaquine. Active monitoring through phone surveys also reduced under-reporting of ADRs. This approach is low-cost, scalable and able to support prioritized activities of the national malaria programme.

Smartphone-based mobile applications for adverse drug reactions reporting: global status and country experience.

BACKGROUND: Smartphone technology can support paperless reporting of adverse drug reactions (ADRs). The aims of this study were to systematically assess smartphone ADR-reporting applications, understand their qualitative and quantitative impact on ADR reporting, and garner key lessons from owners and developers. METHODS: This study had three components: (1) An assessment of ADR-reporting apps, (2) an online survey on the impact of app implementation on ADR reporting and the experiences of app developers and owners, and (3) a search of VigiBase, the World Health Organization global database of individual case safety reports (ICSRs), to observe trends in the number of ADR reports targeting countries where the apps were implemented. RESULTS: Twenty-two apps were included. Eight out of the 22 apps were for countries in the WHO African region. Features observed included E2B data elements (E stands for efficacy) and functions supporting reporting and user engagement. Seventeen app developers and owners answered to the survey and reported overall positive experiences with app features, and post-launch increases in the total number of ICSRs. User type and user environment were cited as factors influencing app use: Respondents said younger people and/or those with an inclination to use technology were more likely to use apps compared to older or more technology-averse people, while respondents in countries with limited internet connectivity reported persistent difficulties in app use. CONCLUSIONS: Smartphone apps for reporting ADRs offer added value compared to conventional reporting tools. Reporting tools should be selected based on interface features and factors that may influence app usage.

Collaboration within the global vaccine safety surveillance ecosystem during the COVID-19 pandemic: lessons learnt and key recommendations from the COVAX Vaccine Safety Working Group.

This analysis describes the successes, challenges and opportunities to improve global vaccine safety surveillance as observed by the Vaccine Safety Working Group from its role as a platform of exchange for stakeholders responsible for monitoring the safety of vaccines distributed through the COVAX mechanism. Three key elements considered to be essential for ongoing and future pandemic preparedness for vaccine developers in their interaction with other members of the vaccine safety ecosystem are (1) the availability of infrastructure and capacity for active vaccine safety surveillance in low-income and middle-income countries (LMICs), including the advancement of concepts of safety surveillance and risk management to vaccine developers and manufacturers from LMICs; (2) more comprehensive mechanisms to ensure timely exchange of vaccine safety data and/or knowledge gaps between public health authorities and vaccine developers and manufacturers; and (3) further implementation of the concept of regulatory reliance in pharmacovigilance. These aims would both conserve valuable resources and allow for more equitable access to vaccine safety information and for benefit/risk decision-making.

Pregnancy exposure registries for drugs and vaccines in low-income and middle-income countries: scoping review protocol.

INTRODUCTION: Data regarding the safety of drugs and vaccines in pregnant women are typically unavailable before licensure. Pregnancy exposure registries (PERs) are an important source of postmarketing safety information. PERs in low-income and middle-income countries (LMICs) are uncommon but can provide valuable safety data regarding their distinct contexts and will become more relevant as the introduction and use of new drugs and vaccines in pregnancy increase worldwide. Strategies to support PERs in LMICs must be based on a better understanding of their current status. We developed a scoping review protocol to assess the landscape of PERs that operate in LMICs and characterise their strengths and challenges. METHODS AND ANALYSIS: This scoping review protocol follows the Joanna Briggs Institute manual for scoping reviews. The search strategy will be reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews Checklist. We will search PubMed, Embase, CINAHL and WHO's Global Index Medicus, as well as the reference lists of retrieved full-text records, for articles published between 2000 and 2022 that describe PERs or other resources that systematically record exposures to medical products during pregnancy and maternal and infant outcomes in LMICs. Title and abstracts will be screened by two authors and data extracted using a standardised form. We will undertake a grey literature search using Google Scholar and targeted websites. We will distribute an online survey to selected experts and conduct semistructured interviews with key informants. Identified PERs will be summarised in tables and analysed. ETHICS AND DISSEMINATION: Ethical approval is not required for this activity, as it was determined not to involve human subjects research. Findings will be submitted to an open access peer-reviewed journal and may be presented at conferences, with underlying data and other materials made publicly available.

A social media intervention for communicating vaccine safety in low- and middle-income countries: protocol for a pilot study.

Vaccine safety is a concern that continues to drive hesitancy and refusal in populations in low-and-middle income countries (LMICs). Communicating about vaccine safety is a strategy that can successfully change personal and community perceptions and behaviors toward vaccination. The COVID-19 infodemic emergency with the rapid rollout of new vaccines and new technology, demonstrated the need for good and effective vaccine safety communication. The Vaccine Safety Net (VSN), a WHO-led global network of websites that provide reliable information on vaccine safety offers the ideal environment for gathering web and social media analytics for measuring impact of vaccine safety messages. Its members work with a wide range of populations, in different geographic locations and at many levels including national, regional, and local. We propose to undertake a pilot study to evaluate the feasibility of implementing COVID-19 vaccine safety communications with VSN members working in LMICs and to assess the impact of communications on public knowledge, attitudes, and perceptions.

The Good Talk! A Serious Game to Boost People's Competence to Have Open Conversations About COVID-19: Protocol for a Randomized Controlled Trial.

BACKGROUND: Vaccine hesitancy is one of the many factors impeding efforts to control the COVID-19 pandemic. Exacerbated by the COVID-19 infodemic, misinformation has undermined public trust in vaccination, led to greater polarization, and resulted in a high social cost where close social relationships have experienced conflict or disagreements about the public health response. OBJECTIVE: The purpose of this paper is to describe the theory behind the development of a digital behavioral science intervention-The Good Talk!-designed to target vaccine-hesitant individuals through their close contacts (eg, family, friends, and colleagues) and to describe the methodology of a research study to evaluate its efficacy. METHODS: The Good Talk! uses an educational serious game approach to boost the skills and competences of vaccine advocates to have open conversations about COVID-19 with their close contacts who are vaccine hesitant. The game teaches vaccine advocates evidence-based open conversation skills to help them speak with individuals who have opposing points of view or who may ascribe to nonscientifically supported beliefs while retaining trust, identifying common ground, and fostering acceptance and respect of divergent views. The game is currently under development and will be available on the web, free to access for participants worldwide, and accompanied by a promotional campaign to recruit participants through social media channels. This protocol describes the methodology for a randomized controlled trial that will compare participants who play The Good Talk! game with a control group that plays the widely known noneducational game Tetris. The study will evaluate a participant's open conversation skills, self-efficacy, and behavioral intentions to have an open conversation with a vaccine-hesitant individual both before and after game play. RESULTS: Recruitment will commence in early 2023 and will cease once 450 participants complete the study (225 per group). The primary outcome is improvement in open conversation skills. Secondary outcomes are self-efficacy and behavioral intentions to have an open conversation with a vaccine-hesitant individual. Exploratory analyses will examine the effect of the game on implementation intentions as well as potential covariates or subgroup differences based on sociodemographic information or previous experiences with COVID-19 vaccination conversations. CONCLUSIONS: The outcome of the project is to promote more open conversations regarding COVID-19 vaccination. We hope that our approach will encourage more governments and public health experts to engage in their mission to reach their citizens directly with digital health solutions and to consider such interventions as an important tool in infodemic management. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/40753.

Smart Safety Surveillance (3S): Multi-Country Experience of Implementing the 3S Concepts and Principles.

INTRODUCTION: The Smart Safety Surveillance (3S) concept is based on the understanding that, when faced with competing pharmacovigilance priorities, countries will have to invest judiciously, by focusing on new priority products, sharing work and resources with other countries when possible and building national competence for those activities that cannot be delegated. METHOD: The 3S principles were applied to Armenia, Brazil, Ethiopia, India, Peru and Thailand using three priority products: bedaquiline, rotavirus vaccine and tafenoquine. A baseline assessment of pharmacovigilance preparedness was used to identify gaps and establish a work plan. The impact was measured by comparing pre and post 3S-intervention outcomes, which included the number and quality of reports (completeness scores) in the WHO global database of Individual Case Safety Reports, VigiBase, and number of structural indicators met. The implementation period was 9-18 months, ranging from March 2018 (earliest started) until May 2020 (latest). RESULT: An increase in adverse drug reaction (ADR) reporting was demonstrated in Armenia (bedaquiline), Brazil (TB and malaria medicines), India (rotavirus vaccine) and Ethiopia (TB medicines). Completeness scores were above 0.5 at baseline in all countries, and reports improved in quality for Brazil (TB), Peru (malaria), Thailand (malaria) and India (immunization). The number of structural indicators met increased by more than double for Ethiopia. Ethiopia and India demonstrated an increased capacity for signal detection and signal evaluation. Armenia, Brazil, Peru and Thailand showed increased capacity to assess risk management plans following the implementation of 3S principles. CONCLUSION: The 3S concept has demonstrated success in different ways across the six countries. Activities focused on three products for a proof of concept of the 3S principles, with the expectation that the project impact will be sustained through strengthened systems, to guide pharmacovigilance activities of other products in the future. It is important to continue monitoring the countries to understand if the gains and successes of the current 3S project are sustainable.

Effect of combined treatment of thioperamide with some antiepileptic drugs on methionine-sulfoximine induced convulsions in mice.

Methionine-sulfoximine (MSO), a convulsant is known to increase the activity of histamine N-methyl transferase. The effect of a selective H3 receptor agonist R- (alpha) methylhistamine (RAMH) and antagonist (thioperamide, THP) and some antiepileptic drugs (gabapentin and sodium valproate) have been evaluated on MSO-induced convulsions in mice. The effect of THP was also evaluated in combination with these antiepileptic drugs. Sodium valproate (300 mg/kg, po) and gabapentin (400 mg/kg, po) offered protection against MSO-induced convulsions as evidenced by a significant prolongation of latency to abnormal dorsoflexion and complete protection against mortality within 6 h of administration. THP (15 mg/kg, ip) alone and in combination with sub-effective doses of gabapentin (75 mg/kg, po) and sodium valproate (75 mg/kg, po) revealed no significant differences from the control group or either drug alone. Hence, the convulsant action of MSO does not appear to be mediated via histaminergic mechanisms.

Thioperamide reduces intracellular calcium in mouse brain synaptosomes.

Intracellular calcium regulation is vital for cells, especially for neurons; raised levels are associated with cytotoxicity and neuronal death. In this report, we present the first experimental evidence showing a concentration-dependent reduction of free calcium in the mouse brain synaptosomes by thioperamide (THP), an H3 receptor antagonist. This is interesting in view of the recent reports on the anticonvulsant and cognition facilitating effects of THP. A neuroprotective potential of THP is suggested.

Adverse Drug Reaction Reporting in Africa and a Comparison of Individual Case Safety Report Characteristics Between Africa and the Rest of the World: Analyses of Spontaneous Reports in VigiBase®.

INTRODUCTION: Following the start of the World Health Organization (WHO) Programme for International Drug Monitoring (PIDM) by 10 member countries in 1968, it took another 24 years for the first two African countries to join in 1992, by which time the number of member countries in the PIDM had grown to 33. Whilst pharmacovigilance (PV), including the submission of individual case safety reports (ICSR) to VigiBase(®), the WHO global ICSR database, is growing in Africa, no data have been published on the growth of ICSR reporting from Africa and how the features of ICSRs from Africa compare with the rest of the world (RoW). OBJECTIVE: The objective of this paper was to provide an overview of the growth of national PV centres in Africa, the reporting of ICSRs by African countries, and the features of ICSRs from Africa, and to compare ICSRs from Africa with the RoW. METHODS: The search and analysis interface of VigiBase(®)--VigiLyze(®)--was used to characterise ICSRs submitted by African countries and the RoW. The distribution of ICSRs by African countries was listed and characterised by anatomic therapeutic chemical (ATC) code, Medical Dictionary for Regulatory Activities (MedDRA(®)) system organ class (SOC) classification, and patient age and sex. The case-defining features of ICSRs between Africa and the RoW were also compared. RESULTS: The number of African countries in the PIDM increased from 2 in 1992 to 35 at the end of September 2015, and African PIDM members have cumulatively submitted 103,499 ICSRs (0.88 % of global ICSRs) to VigiBase(®). The main class of products in African ICSRs are nucleoside and nucleotide reverse transcriptase inhibitors (14.04 %), non-nucleoside reverse transcriptase inhibitors (9.09 %), antivirals for the treatment of HIV infections (5.50 %), combinations of sulfonamides and trimethoprim (2.98 %) and angiotensin-converting enzyme (ACE) inhibitors (2.42 %). The main product classes implicated in ICSRs from the RoW are tumour necrosis factor-α (TNFα) inhibitors (5.29 %), topical nonsteroidal anti-inflammatory preparations (2.26 %), selective immunosuppressants (2.08 %), selective serotonin reuptake inhibitors (2.04 %) and HMG CoA reductase inhibitors (1.85 %). The main SOCs reported from Africa versus the RoW include skin and subcutaneous tissue disorders (31.14 % vs. 19.58 %), general disorders and administration site conditions (20.91 % vs. 30.49 %) and nervous system disorders (17.48 % vs. 19.13 %). The 18-44 years age group dominated ICSRs from Africa, while the 45-64 years age group dominated the RoW. Identical proportions of females (57 % Africa and the RoW) and males (37 % Africa and the RoW) were represented. CONCLUSIONS: As at the end of September 2015, 35 of 54 African countries were Full Member countries of the PIDM. Although the number of ICSRs from Africa has increased substantially, ICSRs from Africa still make up <1 % of the global total in VigiBase(®). The features of ICSRs from Africa differ to those from the RoW in relation to the classes of products as well as age group of patients affected. The gender of patients represented in these ICSRs are identical.

Competition between memory systems: acetylcholine release in the hippocampus correlates negatively with good performance on an amygdala-dependent task.

Lesions of the amygdala impair acquisition of a food conditioned place preference (CPP) task. In contrast, lesions of the fornix facilitate acquisition on this task, showing that an intact hippocampal system can interfere with learning an amygdala-dependent task. Our recent findings indicate that acetylcholine (ACh) release in the hippocampus increases while rats perform a hippocampus-dependent spontaneous alternation task. To the extent that ACh output in the hippocampus reflects activation of that brain area in learning and memory, the results obtained with fornix lesions suggest that ACh release in the hippocampus might be negatively correlated with learning on a CPP task. Using in vivo microdialysis, release of ACh was measured in the hippocampus while rats learned and were tested on an amygdala-dependent CPP task and a hippocampus-dependent spontaneous alternation task. Release of ACh in the hippocampus increased when rats were tested on either task. The magnitude of the increase in release of hippocampal ACh was negatively correlated with good performance on the amygdala-dependent CPP task. These findings suggest that ACh release may reflect activation and participation of the hippocampus in learning and memory, but in a manner that can be detrimental to performance on a task dependent on another brain area.

Modulation of spontaneous alternation performance of mice treated with thioperamide and tacrine in a cross maze task.

A combination of sub-effective doses of thioperamide (7.5 mg/kg, i.p.) and tacrine (0.5 mg/kg, i.p.) enhanced performance in a spatial memory task in mice. This was shown by a significant increase in their spontaneous alternation scores in a cross maze test.

Pharmacovigilance in resource-limited countries.

In the past 20 years, many low- and middle-income countries have created national pharmacovigilance (PV) systems and joined the WHO's global PV network. However, very few of them have fully functional systems. Scientific evidence on the local burden of medicine-related harm and their preventability is missing. Legislation and regulatory framework as well as financial support to build sustainable PV systems are needed. Public health programs need to integrate PV to monitor new vaccines and medicines introduced through these programs. Signal analysis should focus on high-burden preventable adverse drug problems. Increased involvement of healthcare professionals from public and private sectors, pharmaceutical companies, academic institutions and the public at large is necessary to assure a safe environment for drug therapy. WHO has a major role in supporting and coordinating these developments.

The monitoring medicines project: a multinational pharmacovigilance and public health project.

The Monitoring Medicines project (MM), funded by the FP-7 EU framework, was carried out between 2009 and 2013 by a consortium of 11 partners. The objectives were to support and strengthen consumer reporting of adverse drug reactions (ADRs); expand the role and scope of national pharmacovigilance centres concerning medication errors; promote improved use of pharmacovigilance data; and develop methods to complement spontaneous reporting. The work was organised into four themes: patient reporting; medication errors; drug dependence, counterfeit and substandard medicines and clinical risk estimation; and active and targeted spontaneous pharmacovigilance. MM differed from some other major pharmacovigilance initiatives by having participants from developing countries in Asia and Africa and in leaning towards public health and communicable diseases. MM brought together stakeholders including WHO, drug regulators, pharmacovigilance centres, consumers, public health and disease specialists and patient safety networks. Resources and methodologies developed directly by, or with support from, MM include electronic systems/tools for consumer ADR reporting and cohort event monitoring; publication by WHO of handbooks on consumer reporting, medication errors and pharmacovigilance for TB medicines; methodologies for detecting drug dependence and substandard or counterfeit medicines in ADR databases; and a database on HIV treatment risks with a risk assessment tool. MM enabled stakeholders to achieve more than if they had worked alone in pursuit of patient safety.

Targeted spontaneous reporting of suspected renal toxicity in patients undergoing highly active anti-retroviral therapy in two public health facilities in Uganda.

BACKGROUND: Although the national HIV control programme in Uganda has a well-established system for monitoring disease progression and treatment outcomes, monitoring of adverse drug reactions (ADRs) is inadequate. In order to address under-reporting of ADRs, the National Pharmacovigilance Centre, in collaboration with the HIV control programme, piloted a targeted spontaneous reporting (TSR) system as a complementary method to traditional spontaneous reporting. METHODS: From April 2012 to March 2014, all cases of suspected renal toxicity in 10,225 patients on tenofovir-based regimens were monitored in the regional pharmacovigilance centres of Masaka and Mbale. The identification of renal toxicity was performed using serum creatinine, urinalysis, and other signs and symptoms of kidney injury. RESULTS: There was one suspected renal toxicity reported for every 200 patients on a tenofovir-based regimen. Some of the serious reactions reported were death in two cases and bone demineralisation in five patients. Most of patients had been on treatment for 2 years. Those that had been on tenofovir for more than 4 years had raised serum creatinine levels, emphasising the importance of monitoring for the risk of renal damage for longer. We also found that the reporting rate of suspected ADRs for all medicines in the two sites increased almost fivefold during the implementation period. CONCLUSION: Although the occurrence of suspected tenofovir renal toxicity of HIV patients is low, there is need to monitor those at risk so as to prevent irreversible kidney injury. TSR can complement spontaneous reporting for collecting safety data on particular drugs and increase ADR reporting rates.

Experiences and Lessons From Implementing Cohort Event Monitoring Programmes for Antimalarials in Four African Countries: Results of a Questionnaire-Based Survey.

INTRODUCTION: Cohort event monitoring (CEM) is an intensive method of post-marketing surveillance for medicines safety. The method is based on prescription event monitoring, which began in the 1970s, and has since been adapted by WHO for monitoring the safety of medicines used in Public Health Programmes. CEM aims to capture all adverse events that occur in a defined group of patients after starting treatment with a specific medicine during the course of routine clinical practice. OBJECTIVE: The aims of this study were to describe the experiences of National Pharmacovigilance Centres (NCs) that have used CEM to monitor artemisinin-based combination therapy (ACT) for uncomplicated malaria in the African setting, to raise awareness of some of the challenges encountered during implementation and to highlight aspects of the method that require further consideration. METHOD: A questionnaire-based survey was conducted to capture the experiences of NCs that have implemented CEM for active post-marketing surveillance of antimalarial medicines in sub-Saharan Africa. Six NCs were identified as having implemented CEM programmes and were invited to participate in the survey; five NCs indicated willingness to participate and were sent the questionnaire to complete. RESULTS: Four NCs responded to the survey-Ghana, Kenya, Nigeria and Zimbabwe-providing information on the implementation of a total of six CEM programmes. Their experiences indicate that CEM has helped to build pharmacovigilance capacity within the participating NCs and at the monitoring sites, and that healthcare providers (HCPs) are generally willing to participate in implementing the CEM method. All of the programmes took longer than expected to complete: contributing factors included a prolonged enrolment period and unexpectedly slow data entry. All of the programmes exceeded their budget by 11.1-63.2 %. Data management was identified as a challenge for all participating NCs. CONCLUSIONS: The reported experiences of four NCs that have undertaken CEM studies on ACTs indicate that CEM has helped to build pharmacovigilance capacity within NCs and monitoring sites and that HCPs are willing to participate in CEM programmes; however, the method was found to be labour intensive and data management was identified as a challenge. Reducing the workload associated with CEM, particularly in relation to data management, and integrating the method into the routine work of HCPs and NCs should be considered for future implementation.

Effects of folic acid and lamotrigine therapy in some rodent models of epilepsy and behaviour.

It has been suggested that a folic acid (FA) deficiency induced by antiepileptic drugs might be the basis for the neuropsychiatric toxicity associated with these drugs. In the present study, lamotrigine (LTG), one of the newer antiepileptic drugs, was evaluated for its effect on epilepsy, mood and memory in mice. Further, the effect of the addition of FA to LTG therapy was also investigated. The increasing current electroshock seizure test was used to evaluate the anticonvulsant effect of drugs, while the forced swimming test (FST) and spontaneous alternation behaviour (SAB) models were employed for assessing the effects on mood and memory, respectively. LTG exhibited a dose-dependent increase in seizure threshold, whereas FA did not have any effect. LTG did not affect, whereas FA decreased, behavioural depression in the FST in mice. Neither LTG nor FA affected memory scores in the SAB test. The combination of LTG and FA significantly reduced depression while enhancing the effects on memory and seizure threshold. The present observations have confirmed the antiepileptic action of LTG in yet another rodent model of epilepsy. Further, the results clearly demonstrate the additional benefits on epilepsy, mood and memory brought about by the inclusion of FA in the LTG regimen.