Fatigue and Depression in Epilepsy Patients May Not be Solely Related to the Epilepsy Itself

Letter to the Editor

We read with interest the article by Fallatah et al. on a retrospective cross-sectional study on the prevalence of fatigue and depression, as well as influencing factors, in patients with epilepsy (PWE) [1]. Of 259 PWE, 34% reported fatigue and 57% depression [1]. Fatigue correlated positively with female sex, uncontrolled seizures, missed medication, and depression [1]. The study is interesting but raises some questions.

The first point concerns the retrospective study design [1]. Retrospective studies have several disadvantages [2]. These include low data quality, missing data, the inability to demonstrate causality (only associations), susceptibility to memory and selection biases, difficulties in controlling for confounding variables, and a generally lower level of evidence compared to prospective studies [2].

The second point is that factors other than epilepsy and depression that could explain fatigue were not adequately considered and excluded in the study. Fatigue is a common, multifactorial symptom with organic or inorganic causes. Inorganic causes include depression, anxiety, chronic stress and burnout, insomnia, neuroses, and psychoses. Organic causes include diet, lack of exercise, a history of stroke, traumatic brain injury, encephalitis, meningitis, autoimmune diseases, malignancies, restless legs syndrome, Parkinson's disease, heart disease, and endocrinopathies [3]. Before a causal relationship between fatigue and seizures or depression can be established, all other causal factors must be included or excluded in the regression analysis.

Third, the Patient Health Questionnaire (PHQ-9) is not the ideal instrument for diagnosing depression [1]. While the PHQ-9 is suitable for rapid screening and monitoring of treatment effects, it does not provide sufficient emotional assessment [4]. More effective instruments include, for example, the Beck Depression Inventory (BDI), the Hamilton Depression Rating Scale, the CES-D Scale, the MontgomeryÅ sberg Depression Scale, the Geriatric Depression Scale, the Kutcher Depression Scale, the Hospital Anxiety and Depression Scale, the Zung Self-Assessment Scale for Depression, and the Depression and Anxiety Stress Scale.

The fourth point is that only 40% of the included patients were classified as seizure-free [1]. This number is lower than reported in other studies [5]. Normally, at least two-thirds of patients achieve good seizure control. Why did only 40% achieve adequate seizure control in the present study?

The fifth point is that only half of the patients underwent brain MRI to determine whether the seizures were due to a structural brain lesion. Since the ILAE guidelines recommend MRI for all epilepsy patients [6], it needs to be explained why the number of patients who received an MRI was so low [1].

The sixth point is that the study was conducted during the SARS-CoV-2 pandemic. Therefore, it is conceivable that fatigue and depression were exacerbated or even caused by the circumstances at the time of the pandemic and were not related to the epilepsy. Accordingly, it should be clarified how many of the included patients were ever SARS-CoV-2 positive or developed a post-COVID syndrome and whether the seizure frequency increased in SARS-CoV-2-infected individuals.

Finally, it should be clarified what is meant by “epileptic encephalopathy” [1]. Are the authors referring to structural abnormalities in cerebral imaging, or do they mean that other cerebral manifestations were observed in addition to epilepsy? This needs clarification, as it can significantly influence the characterization of the cohort studied.

Acknowledgements

None.