Depression, antiseizure medication side effects take toll on epileptic patients’ quality of life

Among patients with epilepsy, quality of life (QOL) declines with antiseizure medication (ASM) polytherapy, and this effect is mediated by depression and the side effects of ASMs, as reported in a study.

In a cohort of 778 patients with epilepsy, patient-reported depression and ASM side effects jointly mediated the association between ASMs and health-related QOL (HRQOL). These mediators accounted for 42 percent of the total average effect of ASM polytherapy (β, −13.6, 95 percent confidence interval, −18.2 to −8.6) on HRQOL. [Epilepsia 2021;doi:10.1111/epi.17153]

A total of 274 patients (35.2 percent) were receiving multiple ASMs. Compared with those on monotherapy, patients on polytherapy were more likely to have longer disease duration (p<0.01), more ASM side effects (p<0.01), more severe epilepsy (p<0.01), more disabling seizures (p<0.01), and require social assistance (p<0.01). Furthermore, the latter were less likely to drive (p<0.01), be employed (p<0.01), and be free of seizures (p=0.02).

While the goal of epilepsy management with ASMs is achievement of seizure freedom with improved quality of life, addressing ASM side effects and depression may be just as important as addressing seizure control for patients, the investigators pointed out.

“The magnitude of the mediation effects [indicated in the study] emphasizes the need to incorporate measures to assess and treat depression as well as ASM side effects in people with epilepsy, especially those requiring multiple ASMs, [to] improve patients’ overall HRQOL,” they said.

When a patient with epilepsy feels depressed, he is said to be more nervous, restless, and down-hearted. HRQOL inventories reflect social and psychological domains more than the clinical aspects, and such domains represent subjective measures that a patient uses to report on their perception of their HRQOL. This partly explains why in several studies, the presence of depression has been indicated as an essential factor influencing the patient’s judgment concerning his HRQOL. [Ment Illn 2014;6:5169]

Meanwhile, ASM side effects, especially drowsiness and weakness, can have an effect on mental functioning of some patients and thus potentially lower their HRQOL. Often, polytherapy involves complex dosing regimens, which might be bothersome. Some studies have shown that while treatment with some ASMs highly controls seizures, it can lead to memory lapse, motor disorientation, and aggressive behaviour. This indicates that a mere focus on seizure control is not entirely beneficial to the overall QOL of the patient. [Health Qual Life Outcomes 2014;12:49]

“This study … sheds light on the complexity of [the association between ASMs and HRQOL] by identifying the mediating roles of depression and ASM side effects,” they pointed out, adding that theirs is the first exploratory study to examine a causal mediational pathway.

Nevertheless, the study is not without limitations. The investigators acknowledged that the identified mediators may not equally mediate the relationship between ASMs and each specific dimension of HRQOL (eg, seizure worry, social functioning, fatigue). Additionally, this study did not evaluate the patterns and type of polytherapy prescription (eg, two or more old ASMs, two or more new ASMs, or a mix of old and new ASMs).