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Epilepsy: Female sex, refractoriness and clonazepam use associated with depression

Natalia Reoutova
22 Jul 2020

A single-centre retrospective case-control analysis of Hong Kong patients with epilepsy shows that female sex, refractoriness and clonazepam use are risk factors for depression, while valproate use is negatively associated with depression.

Researchers from the Queen Mary Hospital (QMH), Hong Kong, collected and analyzed data from adult patients attending the QMH epilepsy clinic between January and December 2018. Of the patients included in the analysis, 44 had comorbid depression (occurrence rate, 7.9 percent), while 514 patients did not have depression and were used as controls. [Hong Kong Med J 2020, doi: 10.12809/hkmj198310]

“Patients with depression were older, more commonly female, and more commonly exhibited temporal lobe epilepsy,” reported the researchers. The mean age was 58.9 years in patients with depression vs 51.3 years in those without depression (p=0.001). However, the mean age at epilepsy onset did not significantly differ between the groups. Females accounted for 68.2 percent of patients with comorbid depression vs 46.1 percent of patients without depression (p=0.005). Temporal focus was observed in 43.2 percent of patients with comorbid depression vs 25.7 percent of control patients (p=0.012).

“A significantly longer duration of epilepsy was observed in patients with depression,” wrote the researchers. At the time of data collection, the mean duration of epilepsy was 22.7 years among patients with depression vs 17.9 years in patients without depression (p=0.003). In addition, patients with depression used a greater mean number of antiepileptic drugs than those in the control group (2.41 vs 1.73; p=0.003). No differences were noted in other epilepsy-related factors, including family history, drug-resistant disease, seizure frequency, aetiology, seizure type, or history of status epilepticus.

The majority (73 percent) of patients with comorbid depression experienced epilepsy onset before the diagnosis of depression. The mean age (± standard deviation) at epilepsy diagnosis was 35 ± 19 years, while mean age at depression diagnosis was 46 ± 13 years. Almost a third (32 percent) of patients with comorbid depression exhibited drug-resistant epilepsy.

“The relationship between epilepsy and depression is more complex than simple psychological stress related to chronic illness. Structural and functional changes in the brain may explain the underlying pathogenic mechanism,” commented the researchers. [Arch Neurol 1992;49:617-623; Epilepsy Behav 2012;24:156-168]

Binomial logistic regression showed that female sex (odds ratio [OR], 3.56; p=0.01), drug-resistant epilepsy (OR, 4.79; p<0.001) and clonazepam use (OR, 14.41; p<0.001) were significantly positively associated with risk of depression after epilepsy diagnosis, whereas valproate use had a significant negative association with the risk of depression (OR, 0.37; p=0.03).

“Valproate, carbamazepine and lamotrigine are examples of antiepileptic drugs with positive psychotropic effects, whereas benzodiazepines, including clonazepam, have been proposed to induce depression by overinhibition of the GABAergic pathway,” explained the researchers. [Mol Psychiatry 2011;16:383-406; Expert Rev Neurother 2016;16:1321-1333] “Psychotropic properties of antiepileptic drugs should be carefully considered when choosing treatment options for people with epilepsy; clonazepam may promote depression, whereas valproate may protect against depression,” they advised.

“Clinicians who treat patients with epilepsy should be aware of the potential for comorbid depression, especially in patients with potential risk factors, such as female sex, drug-resistant epilepsy and temporal lobe epilepsy,” concluded the researchers.

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