Association of Depression and Treated Depression With Epilepsy and Seizure Outcomes

Abstract

IMPORTANCE A bidirectional relationship exists between epilepsy and depression. However, any putative biological gradient between depression severity and the risk of epilepsy, and the degree to which depression mediates the influence of independent risk factors for epilepsy, has yet to be examined.OBJECTIVE To determine the effect of depression on the risk of epilepsy and seizure outcomes. DESIGN, SETTING, AND PARTICIPANTSAn observational study of a population-based primary care cohort (all patients free of prevalent depression and epilepsy at 18-90 years of age who were active after the Acceptable Mortality Reporting date in The Health Improvement Network database) and a prospectively collected tertiary care cohort (all patients whose data were prospectively collected from the Calgary Comprehensive Epilepsy Programme). The analyses were performed on March 16, 2016. MAIN OUTCOME AND MEASURESThe hazard of developing epilepsy after incident depression and vice versa was calculated. In addition, a mediation analysis of the effect of depression on risk factors for epilepsy and the odds of seizure freedom stratified by the presence of depression were performed. RESULTSWe identified 10 595 709 patients in The Health Improvement Network of whom 229 164 (2.2%) developed depression and 97 177 (0.9%) developed epilepsy. The median age was 44 years (interquartile range, 32-58 years) for those with depression and 56 years (interquartile range, 43-71 years) for those with epilepsy. Significantly more patients with depression (144 373 [63%] were women, and 84 791 [37%] were men; P < .001) or epilepsy (54 419 [56%] were women, and 42 758 [44%] were men; P < .001) were female. Incident epilepsy was associated with an increased hazard of developing depression (hazard ratio [HR], 2.04 [95% CI, 1.97-2.09]; P < .001), and incident depression was associated with an increased hazard of developing epilepsy (HR, 2.55 [95% CI, 2.49-2.60]; P < .001) There was an incremental hazard according to depression treatment type with lowest risk for those receiving counselling alone (HR, 1.84 [95% CI, 1.30-2.59]; P < .001), an intermediate risk for those receiving antidepressants alone (HR, 3.43 [95% CI, 3.37-3.47]; P < .001), and the highest risk for those receiving both (HR, 9.85 [95% CI, 5.74-16.90]; P < .001). Furthermore, depression mediated the relationship between sex, social deprivation, and Charlson Comorbidity Index with incident epilepsy, accounting for 4.6%, 7.1%, and 20.6% of the total effects of these explanatory variables, respectively. In the Comprehensive Epilepsy Programme, the odds of failing to achieve 1-year seizure freedom were significantly higher for those with depression or treated depression.CONCLUSIONS AND RELEVANCE Common underlying pathophysiological mechanisms may explain the risk of developing epilepsy following incident depression. Treated depression is associated with worse epilepsy outcomes, suggesting that this may be a surrogate for more severe depression and that severity of depression is associated with severit...

Anxiety and depression symptoms disrupt resting state connectivity in patients with genetic generalized epilepsies

“…In our cohort, the odds ratio of pharmacoresistance with co‐occurrence of anxiety and depressive symptoms was 7.7, in accordance with a recent report of an odds ratio of 6.1 for refractoriness when patients presented a psychiatric disorder (including depression, anxiety, and schizophrenia) . These results are consistent with our recent temporal lobe epilepsy analyses, as the odds ratio of pharmacoresistance with concurrent anxiety and mood disorders was 4.4, reinforcing the hypothesis of common neurobiological mechanisms between epilepsy and psychiatric disorders . Although the natural idea is that pharmacoresistant seizures cause anxiety and depression, both animal models and population‐based studies have provided evidence of a more bidirectional relationship between psychiatric disorders and epilepsy.…”

“…The impact of the combined symptoms of anxiety and depression on patients’ lives cannot be disregarded, as they may experience stress and sleep problems that can directly influence seizure frequency . A recent population‐based study demonstrated that depression (and treated depression) was associated with poor seizure control, suggesting that “severity of depression is associated with severity of epilepsy.” The complex interaction between epilepsy and psychiatric disorders deserves further investigation and underscores the importance of treating both conditions to improve seizure control and quality of life.…”

Bidirectional relations among common psychiatric and neurologic comorbidities and epilepsy: Do they have an impact on the course of the seizure disorder?

“…An editorial in the same issue of the journal in which the study was published cautioned the readers on the conclusions reached by the Taiwanese investigators, as they had failed to factor‐in the role of the depressive disorder for which the SSRIs were prescribed in the higher risk of epilepsy . In fact, the increased risk of epilepsy identified in this study was comparable to a 2.5 higher risk reported in 2 population‐based studies from the United Kingdom cited earlier …”

“…Several population‐based studies have suggested that primary depression increases the risk of developing epilepsy by twofold and suicidality by three‐ to fourfold, and as indicated above, a mood disorder preceding the onset of epilepsy has been associated with an increased risk of developing treatment‐resistant epilepsy . It follows from these observations that treatment of PCs should be followed by an improved seizure outcome and better tolerance of antiepileptic drugs (AEDs).…”

“…The complex relation among epilepsy, PCs, and NCs may not only be responsible for the higher prevalence rates of PCs and NCs in PWE but may also have an impact on the course of the epilepsy and neurologic disorders. Indeed, patients with a history of depression preceding the onset of epilepsy have an increased risk of developing treatment‐resistant focal epilepsy . By the same token, a history of depression has been associated with a worse course of migraine and stroke .…”