Prophylaxis in bipolar disorder: methodological implications of an almost completed lamotrigine-vs-lithium study

Abstract

Background and Aims

In 2 drug approval studies lamotrigine has been shown to possess prophylactic potentials comparable with lithium in bipolar disorder. However, the generalisabilty of these results are limited. In 2001, an investigator-driven study was initiated comparing lamotrigine and lithium for prophylaxis aiming at mimicking routine clinical conditions. Data collection is not completed (until end 2006) albeit recruitment is accomplished. Based on preliminary findings, the focus will be on methodological implications.

Methods

This is an open, multicenter, randomised trial conducted within the Danish University Antidepressant Group Subjects suffered from bipolar disorder indicating prophylaxis. Exclusion criteria were kept to a minimum. Randomisation took place when clinically appropriate The primary end-point was the need for additional medication or hospitalization, conditionally that patients were stabilized on monotherapy 6 months after randomisation. Patients were followed up to 6 years after randomisation.

Results

Of the 155 randomised patients, 123 (79%) were recruited at the main center. So far, 25% of the patients were prematurely withdrawn within the first 6 months after randomisation, 25% were withdrawn at 6 months since they were not in monotherapy at this point, 25% have reached the primary end-point and the remaining 25% are still in trial.

Conclusions

The large proportion of patients that needed additional medications even after 6 months indicates that previous long-term studies randomising patients on monotherapies may have limited generalisability. The uneven contribution from the main center and the other centers indicates that multicenter studies may include patients that are selected beyond the selection criteria.