Frank Gilliam

Rapid detection of major depression in epilepsy: a multicentre study

BACKGROUND Depression is a common comorbid disorder in epilepsy but is not routinely assessed in neurology clinics. We aimed to create a rapid yet accurate screening instrument for major depression in people with epilepsy. METHODS We developed a set of 46 items to identify symptoms of depression that do not overlap with common comorbid cognitive deficits or adverse effects of antiepileptic drugs. This preliminary instrument and several reliable and valid instruments for diagnosis of depression on the basis of criteria from the Diagnostic and Statistical Manual IV, depression symptom severity, health status, and toxic effects of medication were applied to 205 adult outpatients with epilepsy. We used discriminant function analysis to identify the most efficient set of items for classification of major depression, which we termed the neurological disorders depression inventory for epilepsy (NDDI-E). Baseline data for 229 demographically similar patients enrolled in two other clinical studies were used for verification of the original observations. FINDINGS The discriminant function model for the NDDI-E included six items. Internal consistency reliability of the NDDI-E was 0.85 and test-retest reliability was 0.78. An NDDI-E score of more than 15 had a specificity of 90%, sensitivity of 81%, and positive predictive value of 0.62 for a diagnosis of major depression. Logistic regression showed that the model of association of major depression and the NDDI-E was not affected by adverse effects of antiepileptic medication, whereas models for depression and generic screening instruments were. The severity of depression symptoms and toxic effects of drugs independently correlated with subjective health status, explaining 72% of variance. Results from a separate verification sample also showed optimum sensitivity, specificity, and predictive power at a cut score of more than 15. INTERPRETATION Major depression in people with epilepsy can be identified by a brief set of symptoms that can be differentiated from common adverse effects of antiepileptic drugs. The NDDI-E could enable rapid detection and improve management of depression in epilepsy in accordance with internationally recognised guidelines.

Cognitive effects of topiramate, gabapentin, and lamotrigine in healthy young adults

Objective: To study the acute and steady-state cognitive effects of three new antiepileptic drugs (AEDs): gabapentin, lamotrigine, and topiramate. Background: Several newer antiepileptic medications approved recently by the Food and Drug Administration are gaining attention as efficacious alternatives to established AEDs. Greater tolerability with fewer side effects are reported in some. However, the potential cognitive effects of these newer AEDs have received limited attention. Methods: Healthy young adults randomized to either of the three drugs were administered tests of attention, psychomotor speed, language, memory, and mood at baseline (predrug), acute single-dose period, and after 2 and 4 weeks on the drug. Results: Compared with baseline, the topiramate group had selective, statistically significant declines on measures of attention and word fluency at acute doses, whereas the other two AED groups had no performance changes. At the 2- and 4-week test periods, only the topiramate subjects continued to display neurocognitive effects from drug administration. Conclusions: Results demonstrate potential acute and steady-state adverse cognitive effects for topiramate, whereas minimal effects were displayed for either gabapentin or lamotrigine in young healthy adults.

Patient‐Validated Content of Epilepsy‐Specific Quality‐of‐Life Measurement

Summary: Purpose: To study the effects of epilepsy from the patients’perspective and assist determination of content validity of health‐related quality‐of‐life (HRQOL) measures.

Rates and risk factors for suicide, suicidal ideation, and suicide attempts in chronic epilepsy ☆

Studies of causes of death among people with epilepsy suggest that the lifetime prevalence rate of suicide is elevated. Although not all of the studies have reported an increased risk for suicide, the collective data yield an average rate of approximately 12% among people with epilepsy, compared with 1.1-1.2% in the general population. The increased risk for suicide appears to affect children and adolescents as well as adults. Rates of suicide attempts have also been reported to be elevated among people with epilepsy. A suicide attempt is a significant risk factor for completed suicide. Certain psychiatric disorders, including primary mood disorders, also increase the risk for suicide. Among people with epilepsy, psychiatric comorbidity is common, and rates of mood disorders, particularly major depression, have consistently been reported to be elevated. Other potential risk factors are family issues, physical health, personality, life stress, previous suicidal behavior, and access to firearms. Assessing severity of risk helps to determine the appropriate level of intervention. The suicidality module of the Mini-International Neuropsychiatric Interview is a practical tool to help quantify current suicide risk.

Systematic screening allows reduction of adverse antiepileptic drug effects: A randomized trial

Objective: 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. Methods: 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 of ≥45 were enrolled from a consecutive group of 200 consenting adults with epilepsy. Results: 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%; p < 0.01). 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, p < 0.008). More patients in the AEP group had a >15-point improvement in QOLIE-89 score (p < 0.03). 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. Conclusions: 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.

Adverse effects of antiepileptic drugs

More than 150 years after bromide was introduced as the first antiepileptic drug, adverse effects remain a leading cause of treatment failure and a major determinant of impaired health-related quality of life in people with epilepsy. Adverse effects can develop acutely or many years after starting treatment and can affect any organ or structure. In the past two decades, many efforts have been made to reduce the burden of antiepileptic drug toxicity. Several methods to screen and quantify adverse effects have been developed. Patient profiles associated with increased risk of specific adverse effects have been uncovered through advances in the areas of epidemiology and pharmacogenomics. Several new-generation antiepileptic drugs with improved tolerability profiles and reduced potential for drug interaction have been added to the therapeutic armamentarium. Overall, these advances have expanded the opportunities to tailor treatment with antiepileptic drugs, to enhance effectiveness and minimise the risk of toxic effects.

Improved health care resource utilization following video-EEG-confirmed diagnosis of nonepileptic psychogenic seizures

The economic burden of epilepsy is well recognized. However, empirical investigation establishing costs associated with the diagnosis and treatment of non-epileptic psychogenic seizures (NEPS) is lacking. We studied 20 patients with video/EEG monitoring-confirmed NEPS to determine the effect of definitive diagnosis and treatment on medical costs and utilization. A medical resource utilization questionnaire and inpatient medical chart review were employed to calculate utilization information. Medication usage, outpatient visits, emergency room admissions, and diagnostic testing over a 6-month pre-diagnosis and a 6-month post-diagnosis period were compared. There was an 84% average reduction in total seizure-related medical charges in the 6 months following NEPS diagnosis. Average diagnostic testing charges declined 76%, average medication charges decreased 69%, outpatient clinic visits declined 80%, and emergency room visits reduced by 97%. A majority of patients obtaining a definitive inpatient video/EEG-seizure-monitoring-confirmed NEPS diagnosis experience substantial reductions in health care utilization and dollar costs.

Psychiatric comorbidity, health, and function in epilepsy

Epilepsy is a chronic condition that has complex effects on social, vocational, and psychological function. Several psychiatric disorders have been shown to have increased prevalence in persons with epilepsy compared to the general population. Depression appears to be the most common psychiatric comorbidity, but anxiety and other diagnoses have not been extensively investigated. Several studies have found that depression or psychological distress may be the strongest predictors of health-related quality of life, even including seizure frequency and severity, employment, or driving status. Despite the high prevalence and adverse effects of comorbid psychiatric disorders in epilepsy, very little is known about optimal treatment strategies, or even the efficacy of standard treatments. Further research is needed to increase understanding of the mechanisms of psychiatric illness in epilepsy, the effects of depression and anxiety on long-term clinical outcomes, and the most effective treatments.

Epidemiological and medical aspects of epilepsy in the elderly

Both the incidence and prevalence of epilepsy are high among the elderly. Cerebrovascular disease is the most common underlying cause, although as many as 25-40% of new epilepsy cases in the elderly have no obvious underlying etiology. Status epilepticus appears to occur more frequently in individuals greater than 60 years, and the morbidity and mortality of status epilepticus are significantly greater in this age group. Elderly patients with seizures, particularly complex partial seizures, present differently than younger adults, which can lead to misdiagnosis. Post-ictal confusion may last as long as 1-2 weeks in an elderly patient, as opposed to minutes in younger individuals. Adverse events are similar in symptomatology, but are more common in elderly patients and occur at lower doses and plasma drug concentrations. Neuropsychiatric disorders, such as depression and anxiety, are common in elderly patients with epilepsy, although often under-diagnosed and inadequately treated. The risk of osteoporosis is high among elderly women taking antiepileptic drugs, which underscores the importance of assessing bone health and treatment in this group. Management of the older patient with epilepsy requires an understanding of the etiologies and the medical and psychological aspects unique to this age group.

Patient-oriented outcome assessment after temporal lobectomy for refractory epilepsy

Objective: To determine patient-oriented outcome after anterior temporal lobectomy (ATL) for refractory epilepsy. Background: Health-related quality of life (HRQOL) is an important component of the assessment of outcome from epilepsy surgery, but prior controlled studies of the effect of surgery on HRQOL are inconclusive. Direct assessment of the effect of surgery on patient concerns of living with epilepsy has not been reported. Methods: We used reliable and valid instruments to compare HRQOL and patient concerns of 125 patients who had received an ATL more than than one year previously to a clinically similar group of 71 patients who were awaiting ATL. All patients were selected for surgery based on similar criteria. We also used bivariate correlation analysis and multivariate regression modeling to determine the association of traditional outcome variables with HRQOL. Results: Patients who had undergone ATL reported significantly less concern of living with epilepsy in 16 of 20 items of the EFA Concerns Index and better HRQOL in 8 of 11 scales of the Epilepsy Surgery Inventory-55. Regression analysis in the postoperative group demonstrated that mood status, employment, driving, and antiepileptic drug (AED) cessation, but not seizure-free status or IQ, were associated with better HRQOL. Conclusions: Our findings support a positive affect of ATL on patient concerns and HRQOL in refractory temporal lobe epilepsy, although longitudinal studies are needed to corroborate these results. Mood, employment, driving ability, and AED use are important postoperative predictors of HRQOL.