Antidepressant therapy in epilepsy: can treating the comorbidities affect the underlying disorder?

There is a high incidence of psychiatric comorbidity in people with epilepsy (PWE), particularly depression. The manifold adverse consequences of comorbid depression have been more clearly mapped in recent years. Accordingly, considerable efforts have been made to improve detection and diagnosis, with the result that many PWE are treated with antidepressant drugs, medications with the potential to influence both epilepsy and depression. Exposure to older generations of antidepressants (notably tricyclic antidepressants and bupropion) can increase seizure frequency. However, a growing body of evidence suggests that newer ('second generation') antidepressants, such as selective serotonin reuptake inhibitors or serotonin-noradrenaline reuptake inhibitors, have markedly less effect on excitability and may lead to improvements in epilepsy severity. Although a great deal is known about how antidepressants affect excitability on short time scales in experimental models, little is known about the effects of chronic antidepressant exposure on the underlying processes subsumed under the term 'epileptogenesis': the progressive neurobiological processes by which the non-epileptic brain changes so that it generates spontaneous, recurrent seizures. This paper reviews the literature concerning the influences of antidepressants in PWE and in animal models. The second section describes neurobiological mechanisms implicated in both antidepressant actions and in epileptogenesis, highlighting potential substrates that may mediate any effects of antidepressants on the development and progression of epilepsy. Although much indirect evidence suggests the overall clinical effects of antidepressants on epilepsy itself are beneficial, there are reasons for caution and the need for further research, discussed in the concluding section.

Neuropsychiatric symptomatology predicts seizure recurrence in newly treated patients.

OBJECTIVES: To test the hypothesis that neuropsychiatric symptomatology is predictive of the success of seizure control in patients newly treated with antiepileptic drugs (AEDs), and that this predictive value adds to that provided by other clinical, imaging, and genomic factors in a multivariate model. METHODS: One hundred seventy newly treated patients with epilepsy completed the A-B Neuropsychological Assessment Scale (ABNAS) before commencing AED therapy and were prospectively followed up for 12 months. Patients were classified as nonresponsive if they had at least 1 seizure not explained by medication noncompliance or other significant provoking factors. RESULTS: Of the 138 patients in whom a drug response phenotype at 12 months was able to be determined, nonresponsive patients (n = 45) had a higher pretreatment ABNAS score than patients whose seizures were controlled (n = 93) (p = 0.007). A lesion on MRI was also associated with a higher risk of seizure recurrence (p = 0.003). On multivariate logistic regression, the ABNAS score, the MRI results, and a genomic classifier were all independently predictive of treatment outcome. For AED pharmacoresponse, this multivariate model had diagnostic values of 91% sensitivity, 64% specificity, 84% positive predictive, and 78% negative predictive values. The predictive value of the ABNAS score was validated in a second prospective cohort of 74 newly treated patients with epilepsy (p = 0.005). CONCLUSIONS: The ABNAS provides prognostic information regarding successful seizure control in patients newly treated with AEDs. Furthermore, these results demonstrate the multifactorial nature of the determinants of AED response, with neuropsychological, structural, and genomic factors all contributing to the complex response phenotype.

Epilepsy, depression and antidepressant drugs.

Apart from constituting an important management problem, depression coexisting with epilepsy is also an interesting psychiatric phenomenon, with multiple interacting biological, psychological and social factors involved in its causation. New research approaches to the study of epilepsy and depression, including neuroimaging, neurochemical and neuroendocrine techniques, and the arrival of new classes of antidepressants in recent years, suggest it is timely to reconsider this topic. We review current knowledge of the prevalence and causes of interictal depression in epilepsy, focussing mainly on neurobiological factors, and give an overview of recent concepts concerning the management of depression. We also discuss pharmacological treatment of depression in epilepsy, focussing on the association between antidepressants and seizures, and drug interactions.

Relative-risk-estimate bias and loss of power in the Mantel test for trend resulting from the use of magnetic-field point-in-time ("spot") measurements in epidemiological studies based on an ordinal exposure scale.

We assessed the merits of various point-in-time ("spot") measurement protocols in case-control studies based on an ordinal exposure scale. After classifying a number of houses on the basis of prolonged monitoring of the ambient, extremely low frequency (ELF) magnetic field, we determined the probability of misclassification for each "spot" measurement protocol. We calculated the effect of this misclassification on the relative risk estimates and on the Mantel test for trend. We found that classification based on a small group of point-in-time measurements allows an adequate estimate of the relative risk, although the statistical significance of the dose-response gradient may be seriously underestimated. However, the use of automated ambient-field monitors, which results in loss of information on spatial variability, can lead to similar consequences. Therefore, manually collected point-in-time measurements remain a viable option for exposure assessment.

An analysis of associations between social class and ambient magnetic fields in metropolitan Melbourne.

In the course of a study on residential magnetic-field exposure, some incidental data were obtained that bear on the issue of confounding of magnetic field exposure by social class. We have explored the possibility that the magnetic flux density of 50 Hz fields measured in Melbourne streets is correlated with a number of variables that index the socio-economic status of the neighborhood. We have examined also for a correlation between field-intensity levels and sums of some or all of the indicators, which were weighted to provide an overall score on socio-economic status. Although some of the indexes were weakly, but significantly, correlated with environmental levels of magnetic fields, the combined indices were not. These results indicate that socio-economic status is not likely to be a confounder in epidemiological studies of residential exposure to ELF magnetic fields in Melbourne.

The use of 'spot' measurements in epidemiological studies of the health effects of magnetic field exposure.

In several countries, epidemiological studies are being planned, or are in progress, to test the hypothesis that a causal relation exists between exposure to extremely low frequency magnetic fields and cancer incidence. One of the major difficulties in these studies is the development of valid and efficient protocols to assess magnetic field exposure. In studies focusing on residential magnetic fields, many researchers are turning to recently developed stationary automated magnetic field monitors to characterize exposure. We argue that a relatively small number of manually collected 'spot' measurements may be an adequate alternative which has several advantages. We compared a dichotomous exposure classification based on continuous magnetic field monitoring of 40 houses with that obtained through 'spot' measurements randomly sampled from the continuous records. We found that a single spot measurement had at least an 80% chance of classifying houses correctly and that this probability did not increase significantly as the number of readings was increased. We also calculated the sensitivity and specificity of various simulated measurement protocols and, from these, the effect of misclassification on estimates of relative risk. Since relatively large spatial variations in background magnetic field exist in many homes, we suggest that a small number of readings collected manually at several points within a residence may characterize the magnetic field better than continuous monitoring at one fixed location.

Physician assistants in emergency medicine.

Physician assistants (PAs) specially trained in emergency medicine can be used effectively to work with emergency medicine physicians to provide efficient and expedient high-quality patient care. The concept of using PAs in the emergency department is reviewed, and items of concern to professionals who are reluctant to use PAs are discussed. Financial issues and malpractice risk are examined, and our experience with patient perceptions is summarized. The PA program at Beth Israel Medical Center is used as a case study to demonstrate the use and integration of the PA within the division of emergency services. Although a well-trained emergency physician is the gold standard for quality patient care, cost-effective quality care for certain patient complaints can be rendered acceptably by others.

Evaluation of the automated leukocyte differential count in emergency department patients.

This study compares the results of the leukocyte three-part differential count as determined by the Coulter S-Plus IV in 104 consecutive patient samples from the emergency department with results obtained by conventional visual differential. A high rate (40%) of instrument rejection was found, reflecting the high prevalence of disease and hematologic abnormalities in the patient population. No clinically significant abnormality went undetected, demonstrating that the automated leukocyte three-part differential is effective as a screening test in the emergency department patient population.

Dissecting thoracic aortic aneurysm in a 16-year-old.

A 16-year-old boy presented with a one-hour history of left lower extremity pain and weakness, and was found to have a dissecting aortic aneurysm. The patient underwent emergency aortic angiography and immediate reparative aortic aneurysm surgery. He died on the fifth postoperative day. Because the majority of cases occur in the fifth to sixth decade of life, dissecting aortic aneurysm is a rare and usually fatal condition in adolescents. Potentially favorable outcome in this age group depends on prompt diagnosis and immediate medical and surgical intervention.

Propranolol overdose.

This is a report of a patient who survived a large propranolol overdose, as documented by toxic blood levels. The signs and symptoms were those of profound inotropic and moderate chronotropic cardiotoxicity which failed to respond to parasympatholytics or catecholamines, but subsequently reversed coincident with the administration of glucagon. We report this case because of the sudden development of shock in a patient who looked deceptively well, and because of the improvement apparently brought about by glucagon.