Current limitations of XXXX therapy: a conference review.

@entity1 @entity410 @entity734 @entity302
The current limitations of @entity734 ( @entity734 ) therapy were the topic of a discussion group meeting at the 5th European Congress on Epileptology, Madrid, 6-10 October 2002. This review contains four short papers covering the topics discussed by the speakers at this meeting and an account of the ensuing discussion with all @entity1 . The meeting focused on four issues. (i) Are mechanisms of action of AEDs useful to predict treatment outcome? The short answer to this question was no, for several reasons. These include the fact that clinically relevant mechanisms in individual @entity1 remain unclear, the treatment of @entity302 targets the symptoms rather than the cause of the disease, and that current @entity410 classification defines heterogeneous @entity1 populations. (ii) The benefits of the often recommended titration of the dose to the maximum tolerated level when @entity410 persist at average @entity734 doses. A re-evaluation of this practice showed that dose escalation achieves @entity410 freedom in only 1 of 4 @entity1 with newly diagnosed @entity302 and only 1 of 10 @entity1 with @entity302 are likely to experience a greater than 50% reduction in @entity410 frequency. Being aware of the limited utility of maximum dose titration and subsequent dose reduction if no significant individual benefit is achieved avoids medical over-treatment with a worsening risk-benefit balance. (iii) When single drug therapy is not sufficiently effective, adding a second drug or alternative monotherapy are common options. Based on published data, there is no conclusive evidence in favour of either alternative monotherapy or second-line polytherapy. A pragmatic choice may be to evaluate the combination and then attempt to withdraw the first drug in the case of success. This may prevent the substitution of a partially efficacious drug by a non-efficacious drug. The choice of the second drug should, in theory, be based on which first drug has failed but again compelling evidence to support specific recommendations is lacking. (iv) Unexpected worsening of @entity410 may occur in many circumstances and has many causes, including tolerance and adverse pharmacodynamic effects of individual AEDs on @entity410 generating mechanisms. @entity1 are usually aware of aggravation and may express a "dislike" for a particular @entity734 as a warning sign for physicians to modify the medication. The availability of numerous AEDs, particularly with single mechanisms of action, has increased the risk of paradoxical effects that may go undetected in clinical trials and only surface during astute clinical observations.
