Background and ObjectiveOf ~5 million people living with epilepsy (PLWE) in Sub‐Saharan Africa, roughly one‐third experience depression and over one third experience anxiety. In Guinea, these issues may be compounded by fewer available resources, such as appropriate anti‐seizure medications (ASMs). We aim to quantify seizure frequency, anxiety and depression in PLWE in Guinea, before and after a free ASM intervention and neurologist's consultation.MethodsGuinean participants >12 years old with ≥2 unprovoked seizure were prospectively recruited. As part of a broader interview, participants reported prior 30‐day seizure frequency and screened for depression (PHQ‐9) (range 0–27 points) and anxiety (GAD‐7) (range 0–21 points) with re‐evaluation at 90 days.ResultsOf 148 participants enrolled (mean age = 27.3 years, range 12–72; 45% female), 62% were currently taking ASMs. For the 30 days pre‐enrolment, average seizure frequency was 3.2 (95%CI 2.3, 4.2); 28% of participants were seizure‐free. ASM regimens were modified for 95% of participants, mostly initiating levetiracetam (n = 115, 80% of modifications). 90‐day study retention was 76% (n = 113) among whom 87% reported full adherence to the ASM. After 90 days, the average seizure frequency over the prior 30 days was 1.5 (95%CI 0.5, 2.6), significantly lower than at baseline (p = 0.002). 66% were seizure‐free.At baseline, average PHQ‐9 score was 21.2 (95%CI [20.2, 22.2]), indicating severe depressive symptoms. Average GAD‐7 score was 16.5 [15.6, 17.4], indicating severe anxious symptoms. At 90‐days, average PHQ‐9 score was 17.5[16.4, 18.5] and significantly lower than baseline (p < 0.001). Average GAD‐7 score was 14.4 [13.6, 15.3] and significantly lower than baseline (p = 0.002). Seizure frequency was not correlated with PHQ‐9 nor GAD‐7 scores at baseline but was at 90 days for both PHQ‐9 (r = 0.24, p = 0.01) and GAD‐7 (r = 0.22, p = 0.02) scores. The prevalence of suicidal ideation dropped from 67% to 47% of participants (p = 0.004).DiscussionASM management has dual importance for PLWE in resource‐limited settings, improving both seizure control and mental health.