The efficacy of an antiepileptic drug (AED) is determined at present by the drug-elicited reduction in seizure frequency. Reduction of seizure frequency as the sole measure of efficacy does not account for treatment-induced reductions in seizure severity and positive psychological effects experienced by the patient. A clinical trial was undertaken in which seizure frequency was the primary and seizure severity and psychological well-being were the secondary measures of efficacy. Psychological assessment and seizure frequency were monitored in patients whose epilepsy was treated with lamotrigine (LTG) or placebo. The results indicate that LTG is an effective AED, causing reductions in seizure frequency and severity and improvements in mood and mastery. In addition, the study demonstrated that the use of seizure severity scales, especially the Ictal subscale, may enhance the sensitivity of assessment of trials of AED treatments.

The impact of a chronic illness is experienced not only through its physical symptoms, but also as a result of its effect on psychosocial functioning. In the case of an illness such as epilepsy, where the physical manifestations are transient, the psychosocial consequences may, with time, come to be of greater concern. We have been involved in developing a quality of life model for epilepsy. As part of the refinement of the initial model, we have devised a novel scale to measure the impact of the condition on a number of different aspects of daily life. The scale was administered to 75 patients attending an epilepsy out-patient clinic. Initial analysis of its psychometric properties is encouraging, although the inclusion of an item relating to employment reduced the scale's reliability. As a result, the wording of the existing item has been amended and an additional item has been incorporated. We hope the scale will be useful in investigations of treatment for epilepsy and of its psychosocial aspects.

Summary: The need for new antiepileptic drugs (AEDs) and more sensitive methods of assessing their efficacy is well recognized. This study was designed to evaluate the efficacy and safety of lamotrigine (LTG), a potential new AED and to develop and test new outcome measures. A health‐related quality of life (HRQL) model was developed which contains previously validated measures of anxiety, depression, happiness, overall mood, self‐esteem, and mastery and a specifically designed seizure severity scale with patient‐ and caregiver‐based components. This HRQL model was used in a randomized, placebo‐controlled, double‐blind, cross‐over study of LTG in 81 patients with refractory partial seizures. Seizure frequency was the primary measure and seizure severity and the HRQL were secondary measures of efficacy. The reduction in seizure frequency with LTG, relative to placebo, was 29.7% [95% confidence interval (CI) 17.8%, 39.9%] for total seizure count, 33.4% (95% CI 14.8%, 47.9%) for complex partial seizures (CPS) and 20.3% (95% CI 0.3%, 36.2%) for secondarily generalized tonic‐clonic seizures (GTCS). However, although 41 patients elected to continue with LTG, only 11 experienced at least 50% reduction in total seizures, indicating that other factors influenced their decision. The score with LTG, relative to placebo, was significantly lower for the ictal (p = 0.017) and caregivers (p = 0.035) subscales of the seizure severity scale and significantly higher for happiness (p = 0.003) and mastery (p = 0.003). Simple correlation and multiple‐regression analyses indicate that the effects on seizure frequency, seizure severity, and psychological variables appear to be independent of each other. This study indicates that LTG is effective in reducing seizure frequency and has additional favorable effects on seizure severity, mood, and perceived internal control. Some of the scales used indicate the potential of secondary measures of efficacy to enhance the sensitivity of trials of new AEDs.