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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

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.

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.

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 TLE patients. 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 to 57% of the subjects in the upper three quartiles (p< 0.008). No other limbic brain structures that we assessed: 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 hyerexcitable neuronal influence on the limbic network.

The objective of this study was to determine prevalence and predictive risk factors of suicidality in a large sample of epilepsy outpatients. We prospectively examined 193 consecutive adult epilepsy outpatients for depression, including suicidal ideation. Demographic and epilepsy factors, medication toxicity and health-related quality of life were also evaluated. The prevalence of suicidal ideation within the past two weeks was 11.9%. Although medication toxicity, health-related quality of life and BDI scores were each associated with suicidal ideation in the bivariate analyses, only the BDI remained significant in the logistic regression analysis. About one-fourth of the subjects with suicidal ideation had no significant symptoms of depression. Recent thoughts of suicide are a common occurrence in the outpatient epilepsy clinic setting, but these are not predicted by gender, age, seizure factors, medication toxicity or self-perceived quality of life. Although depression is associated with suicidal ideation, about one-fourth of the suicidal subjects were euthymic or only mildly depressed.

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. AE = adverse effect; AED = antiepileptic drug; AEP = Adverse Event Profile; BDI = Beck Depression Inventory; GABA = γ-aminobutyric acid; HRQOL = Health-Related Quality of Life; QOLIE = Quality of Life in Epilepsy Inventory.

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.

To determine the effectiveness of systematic screening with a brief 19-item self-report instrument, the Adverse Events Profile (AEP), to reduce adverse effects of antiepileptic drugs (AEDs) and improve subjective health status.The authors performed a prospective randomized trial comparing the use of the AEP with usual care without the AEP. Sixty-two patients with an AEP score ofor=45 were enrolled from a consecutive group of 200 consenting adults with epilepsy.The mean percent improvement in AEP scores was greater in the patient group for which clinicians received the AEP compared with the usual care group (25% vs 5%; p0.01). Mean change in Quality of Life in Epilepsy Inventory (QOLIE)-89 total scores was not different between groups, but for the entire sample QOLIE-89 change was greater for patients having a 15-point improvement in AEP scores than for those with a 0- to 15-point improvement or a worsened score (24 vs 12 vs 3; analysis of variance, p0.008). More patients in the AEP group had a15-point improvement in QOLIE-89 score (p0.03). Use of the AEP was associated with a 2.8-fold increase (95% CI, 1.7 to 4.8) in AED modifications. No difference in seizure rates was observed.Systematic screening for antiepileptic drug side effects may increase identification of toxicity and guide medication changes to reduce adverse effects and possibly improve subjective health status.

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.

Patients with epilepsy have a higher prevalence of depressive disorders than the general population, but the relationship between seizure rates and depression has not been adequately studied. We used the Beck Depression Inventory to evaluate depressive symptoms in 143 consecutive epilepsy patients from outpatient clinics. Patients who were seizure free more than 6 months were considered not intractable. Thirty-six percent were neither intractable nor depressed, 43% had intractable epilepsy and were not depressed, 10% had intractable epilepsy and were depressed, and 11% did not have intractable epilepsy and were depressed. Patients with epilepsy have a higher prevalence of depression than the general population, but the intractability of the seizure disorder does not seem to be an independent risk factor for the occurrence of depression. There is no relationship between the severity of depression and monthly seizure rate.