A Trial of Sertraline or Cognitive Behavior Therapy for Depression in Epilepsy.

OBJECTIVE: Limited evidence is available to guide treatment of depression for persons with epilepsy. We evaluated the comparative effectiveness of sertraline and cognitive behavior therapy (CBT) for depression, quality of life, seizures, and adverse treatment effects. METHODS: We randomly assigned 140 adult outpatients with epilepsy and current major depressive disorder to sertraline or weekly CBT for 16 weeks. The primary outcome was remission from depression based on the Mini International Neuropsychiatric Interview (MINI). Secondary outcomes included the Quality of Life in Epilepsy Inventory-89 (QOLIE-89) seizure rates, the Adverse Events Profile (AEP), the Beck Depression Inventory, and MINI Suicide Risk Module. RESULTS: In the intention-to-treat analysis, 38 (52.8%; 95% confidence interval [CI] = ±12) of the 72 subjects assigned to sertraline and 41 (60.3%; 95% CI = ±11.6) of the 68 subjects in the CBT group achieved remission; the lower bound of efficacy for both groups was greater than our historical placebo control group upper bound of 33.7%. Difference in time to remission between groups was 2.8 days (95% CI = ±0.43; p = 0.79). The percent improvement of mean QOLIE-89 scores was significant for both the CBT (25.7%; p < 0.001) and sertraline (28.3%; p < 0.001) groups. The difference in occurrence of generalized tonic-clonic seizures between groups was 0.3% (95% CI = ±8.6; p = 0.95). Suicide risk at final assessment was associated with persistent depression (p < 0.0001) but not seizures or sertraline. INTERPRETATION: Depression remitted in just over one-half of subjects following sertraline or CBT. Despite the complex psychosocial disability associated with epilepsy, improving depression benefits quality of life. Serotonin reuptake inhibition does not appear to increase seizures or suicidality in persons with epilepsy. ANN NEUROL 2019;86:552-560.

Severe hippocampal atrophy is not associated with depression in temporal lobe epilepsy.

Depression in temporal lobe epilepsy (TLE) is common, is a strong predictor of subjective disability, and may have unique pathophysiological characteristics. Previous studies showed that reduced hippocampal volume is associated with significant depressive symptoms in patients with TLE. We utilized regions of interest analysis of high-resolution brain MRI and a reliable and valid measure of depressive symptoms to evaluate 28 consecutive adult subjects with video-EEG-confirmed TLE. Regions of interest were based on prior human and animal studies of mood and behavioral dysfunction. Forty-three percent of the entire group had significant symptoms of depression, defined by a Beck Depression Inventory (BDI) score of greater than 15. Total hippocampal volumes were significantly smaller in the group with BDI<15, (p<0.007). None of the subjects in the quartile with the smallest left hippocampal volume had a BDI score greater than 15 compared with 57% of the subjects in the upper three quartiles (p<0.008). No other limbic brain structures (amygdala, subcallosal gyrus, subgenual gyrus, gyrus rectus), or total cerebral volume were associated with depressive symptoms. Adequate hippocampal integrity may be necessary to maintain depression symptoms in mesial temporal lobe epilepsy. This finding also supports the possibility of a unique mechanism for depression in mesial temporal lobe epilepsy, such as hyperexcitable neuronal influence on the limbic network.

The relationship of sleep disturbances and fatigue in multiple sclerosis.

BACKGROUND: Fatigue is experienced by most patients with multiple sclerosis (MS) and often is profoundly debilitating. No large-scale studies to our knowledge have examined circadian rhythm abnormalities in MS patients or the relationship of fatigue to circadian rhythms. OBJECTIVE: To determine if patients with MS and fatigue have sleep disturbances or circadian rhythm abnormalities associated with fatigue. DESIGN: Case-control study. SETTING: Washington University School of Medicine, St Louis, Mo. PATIENTS: Fifteen patients with MS and fatigue were compared with 15 patients with MS without fatigue and 15 age- and sex-matched, healthy controls. MAIN OUTCOME MEASURES: Sleep disturbances and circadian rhythm abnormalities were quantitated by actigraphy, fatigue by the Fatigue Descriptive Scale, and excessive sleepiness by the Epworth Sleepiness scale (ESS). RESULTS: Of the 15 fatigued patients with MS, 2 had delayed sleep phase, 10 had disrupted sleep, and 3 had normal sleep. One of the 15 nonfatigued MS patients had irregular sleep cycles, 2 others had disrupted sleep, and 12 had normal sleep. All 15 of the healthy controls had normal sleep. Nine patients with MS and fatigue scored 10 or higher on the ESS, suggesting excessive daytime sleepiness. Only 2 patients with MS without fatigue scored higher than 10 on the ESS. None of the healthy controls were fatigued, and 14 were not excessively sleepy. A relationship was found between fatigue and abnormal sleep cycles or disrupted sleep (Fisher exact test, P =.003). There was also a relationship between subjective excessive daytime sleepiness and fatigue in MS patients (P =.02). CONCLUSION: There is a significant correlation between fatigue in MS patients and disrupted sleep or abnormal sleep cycles.

Adverse antiepileptic drug effects: toward a clinically and neurobiologically relevant taxonomy.

BACKGROUND: Adverse effects (AEs) of antiepileptic drugs (AEDs) are a major impediment to optimal dosing for seizure control. Better understanding of clinical properties of AEs is a prerequisite for systematic research of their neurobiological underpinnings. This study aimed to define specific patterns of AE occurrence and determine their clinical relevance based on their association with subjective health status. METHODS: Two hundred subjects with epilepsy completed validated self-report health assessments, including the Adverse Event Profile (AEP) and Quality of Life in Epilepsy Inventory (QOLIE)-89. Factor analysis was performed on the 19 AEP items to identify distinct classes of AEs. Correlations between AE class scores and QOLIE-89 scores were evaluated. Multivariate analysis was used to assess contributions of AE class scores to QOLIE-89 scores after controlling for depression and seizure frequency. Relationships between changes in AE class scores and changes in QOLIE-89 scores were also investigated in a subgroup of 62 subjects enrolled in a randomized trial. RESULTS: The mean number of AEs per subject was 6.5. AEs were segregated into five classes: Cognition/Coordination, Mood/Emotion, Sleep, Weight/Cephalgia, and Tegument/Mucosa. Higher scores in each AE class were associated with lower QOLIE-89 scores. Cognition/Coordination scores were the strongest predictor of QOLIE-89 scores. Improvements in Cognition/Coordination, Mood/Emotion, and Tegument/Mucosa scores were associated with improvements in QOLIE-89 scores. Improved Cognition/Coordination was the only predictor of improved QOLIE-89. CONCLUSION: Adverse effects (AEs) of antiepileptic drugs can be classified in five biologically plausible factors. When specific classes of AEs are identified and attempts are made to reduce them, quality of life is significantly improved.

Tolerability of antiseizure medications: implications for health outcomes.

Epilepsy is a disorder of abnormal excitability and synchronicity of aggregates of neurons that lead to paroxysmal behavioral or perceptual change. Most antiepileptic drugs (AEDs) decrease membrane excitability or increase postsynaptic inhibition, and may alter synchronization of neuronal networks. The attributes of an AED that reduce the tendency toward seizures may cause disruption of normal cerebral processes. Previous clinical studies suggest wide inter-individual variability of the effects of such AEDs. The options for antiepileptic treatment have dramatically expanded in the past decade and now allow tailoring of intervention for optimal management of individual patients. Current strategies to improve epilepsy care should include systematic monitoring to identify adverse effects of AEDs, and future approaches may involve creative applications of neuroimaging and genetic technologies to match patient characteristics to AED attributes.

Video EEG monitoring prior to vagal nerve stimulator implantation.

Vagal nerve stimulation (VNS) is a safe alternative therapy for epilepsy but may have rare significant complications. There is no consensus regarding the necessity of video-EEG monitoring to characterize events before the VNS implantation. The authors discuss four patients who were inappropriately referred for or implanted with VNS without any previous video-EEG monitoring, in the context of their entire case experience.

Depression in epilepsy: ignoring clinical expression of neuronal network dysfunction?

Epilepsy is a chronic disorder that adversely affects social, vocational, and psychological functioning. Despite the variety and complexity of the negative clinical associations with epilepsy, depression is remarkable in prevalence and related adverse effects on health status. An estimated 30-50% of persons with refractory epilepsy have major depression, and depression has a stronger correlation than seizure rate with quality of life. Suicide is one of the leading causes of death in epilepsy. Available data indicate that depression may result from underlying brain dysfunction rather than social and vocational disability. Most patients with depression are not screened systematically for the diagnosis, and are subsequently not treated. Although the density of serotonin receptors is greatest in limbic brain regions commonly involved in human epilepsy, such as the mesial temporal and prefrontal areas, no prior randomized controlled trials have evaluated the efficacy of serotonin reuptake inhibitors for depression in epilepsy.