BackgroundComorbid mental health conditions are common in people with epilepsy and have a significant negative impact on important epilepsy outcomes, although the evidence is mostly from high-income countries. This systematic review aimed to synthesise evidence on the association between comorbid mental health conditions and quality of life and functioning among people with epilepsy living in low- and middle income countries (LMICs).MethodsWe searched PubMed, EMBASE, CINAHL, Global Index medicus (GID) and PsycINFO databases from their dates of inception to January 2022. Only quantiative observational studies were included. Meta-analysis was conducted for studies that reported the same kind of quality of life and functioning outcome. Cohen's d was calculated from the mean difference in quality-of-life score between people with epilepsy who did and did not have a comorbid depression or anxiety condition. The protocol was registered with PROSPERO: CRD42020161487.ResultsThe search strategy identified a total of 2,101 articles, from which 33 full text articles were included. Depression was the most common comorbid mental health condition (33 studies), followed by anxiety (16 studies). Meta-analysis was conducted on 19 studies reporting quality of life measured with the same instrument. A large standardized mean effect size (ES) in quality of life score was found (pooled ES = -1.16, 95% confidence interval (CI) - 1.70, - 0.63) between those participants with comorbid depression compared to non-depressed participants. There was significant heterogeneity between studies (I-2 = 97.6%, p < 0.001). The median ES (IQR) was - 1.20 (- 1.40, (- 0.64)). An intermediate standard effect size for anxiety on quality of life was also observed (pooled ES = -0.64, 95% CI - 1.14, - 0.13). There was only one study reporting on functioning in relation to comorbid mental health conditions.ConclusionComorbid depression in people with epilepsy in LMICs is associated with poor quality of life although this evidence is based on highly heterogeneous studies. These findings support calls to integrate mental health care into services for people with epilepsy in LMICs. Future studies should use prospective designs in which the change in quality of life in relation to mental health or public health interventions across time can be measured.