The Neuropsychiatric Loop in Juvenile Myoclonic Epilepsy: How Depression Drives Treatment Resistance — Experience from a Tertiary Referral Center in LATAM
Stefan Narváez-Labuhn1, Juan Carlos Vera-Lopez1, Maximiliano Salgado-Deza1, Fernando Vasquez Lopez1, Salvador Martínez-Medina1, Katherin Milagros Plasencia Correa1, Mariana Peschard-Franco1, Andres Felipe Morcillo Muñoz1, Mario A. Sebastian-Diaz2, Iris E. Martínez Juárez1
1Epilepsy Clinic & Clinical Epileptology Fellowship, National Institute of Neurology and Neurosurgery and UNAM, Mexico city, Mexico, 2Department of Nephrology, Central South High Specialty Hospital
Objective:
To examine the bidirectional association between seizure freedom and depression in patients with juvenile myoclonic epilepsy (JME), testing the hypothesis of a “neuropsychiatric loop” linking affective burden and seizure control. Understanding this dynamic interplay may clarify mechanisms that sustain treatment resistance and inform integrated neuropsychiatric care.
Background:
Depression is highly prevalent in JME and has been linked to poorer seizure outcomes. However, the reverse direction of whether persistent seizures increase the likelihood of depression remains underexplored. This study builds upon our previous analysis of psychiatric comorbidities in JME (“The Burden of the Mind in Epilepsy”), focusing specifically on the reciprocal interaction between depression and seizure freedom.
Design/Methods:
Depression was analyzed as the main dependent variable in 145 patients with JME. Seizure freedom was the primary predictor, and polytherapy (≥3 ASMs) served as a marker of treatment resistance. Binary logistic regression models, both crude and adjusted for demographic and clinical covariates, were used to estimate odds ratios (ORs, 95% CI).
Results:
Depression was identified in 22.8% (n=33) of participants. Patients not seizure free were significantly more likely to exhibit depression (p = 0.019; OR = 1.77, 95% CI = 1.03–3.05). In logistic regression, lack of seizure freedom independently predicted depression (adjusted OR = 2.59, 95% CI = 1.09–6.13, p = 0.030). Greater ASM number correlated inversely with seizure freedom (p ≤ 0.002).
Conclusions:
Depression and seizure control exhibit a self-reinforcing, bidirectional relationship in JME. Lack of seizure freedom increases the likelihood of depression, forming a “neuropsychiatric loop” that perpetuates treatment resistance. Psychiatric comorbidities may not be merely secondary but core correlates of treatment resistance. These findings highlight the need for integrated neuropsychiatric management to disrupt this cycle and improve long-term outcomes in JME.
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