Monday, September 15, 2008

New screening tool for identifying major depression in patients with epilepsy

Major depression is a common comorbidity with epilepsy, with an estimated prevalence of 20–55% in those with chronic epilepsy.

Although depression is often treatable, it is under-diagnosed by neurologists and primary-care physicians in the setting of chronic neurological disease. Depression is an important contributor to decline in perceived health status, causes significant functional and psychosocial disability, and might lead to suicide or self-injury. Recognition of depression in patients with epilepsy can be especially difficult because of the effect of the primary illness on mood, cognition and memory function, and because of the adverse effects of anticonvulsant drugs, some of which can mimic symptoms of depression.

Clinical diagnosis is a hypothesis-driven iterative process that involves the consideration of a specific diagnosis, data gathering and analysis to support or refute the hypothesis, refinement of the hypothesis, reanalysis of available data and a directed search for additional data, and ultimately confirmation of a specific diagnosis.

Diagnostic errors can arise from misinterpretation of data, omission of critical tests, or unusual features of an individual’s clinical presentation, but perhaps the most serious errors arise from a failure to even consider the correct diagnosis in the process of hypothesis generation.

Robust diagnostic screening tools are particularly useful in reducing the frequency of the last of these errors. An ideal screening tool should be sensitive, specific, easy to use, inexpensive, and validated in a sample of the population to be screened. The tradeoff between sensitivity and specificity must be negotiated in the context of the ‘cost’ of false negatives and false positives.

Gilliam and colleagues used rigorous methods to develop and test a screening tool for major depression in patients with epilepsy. Beginning with an inventory of 46 items selected to identify symptoms of depression that were unlikely to be influenced by cognitive deficits and drug-related adverse events, they applied a discriminant function analysis to identify six items that together efficiently identified patients with depression.

They defined appropriate statistical boundaries to maximize sensitivity (81%) and specificity (90%), documented internal consistency and test–retest reliability, and validated the screen in a larger independent sample of patients with epilepsy. The resultant NDDI-E screen is brief, simple to administer and score, and costs nothing. An important strength of this work derives from the authors’ broad experience in assessing mood disorders in the context of neurological disease, and their sensitivity to the problem of potential false positives that could result from the disease itself or from its treatment, but that do not reflect genuine depression. These potential false positives are important to avoid, because it is unlikely that targeted antidepressant treatment would help improve secondary symptoms.

A limitation of the study is that all patients— those in the initial screen-development study and those in the validation study—were drawn from tertiary-care epilepsy centers, and this population is not fully representative of the broader population of patients with epilepsy. Patients with refractory epilepsy in particular might have a higher incidence of depression than those with good seizure control, and the sensitivity and specificity of a screening test are likely to be altered by the prior probability of having the condition detected by the screen.

The utility of the NDDI-E should, therefore, be monitored in a community-based population. Ultimately, however, the value of the tool depends not only on its accuracy and ease of use, but also on the availability of effective treatments and a clear management plan for the specific type of major depression that affects patients with epilepsy.


Ettinger A et al. (2004) Depression and comorbidity in community-based patients with epilepsy or asthma. Neurology 63: 1008–1014

Gilliam FG et al. (2004) Depression in epilepsy: ignoring clinical expression of neuronal network dysfunction? Epilepsia 45 (Suppl 2): S28–S33 3 Getz K et al. (2002) Negative symptoms in temporal lobe epilepsy. Am J Psychiatry 159: 644–651

AJ Cole is Director of the Epilepsy Service and Chief of the Epilepsy Research Laboratory at Massachusetts General Hospital, Boston, MA, USA.

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