Background

Epilepsy is a complex neurological condition responsible for considerable morbidity and mortality. It affects over 400,000 individuals within the UK and is responsible for over 1000 deaths per year. Initial treatment approaches focus on drug therapy, either monotherapy or adjunctive therapy. In the event of drug treatment failure, surgery might be considered but is limited to a very specific group of patients. Drug therapy is, therefore, the mainstay of treatment. Because many individuals can require many years of, if not lifelong, treatment with antiepileptic drugs (AEDs), the clinical effectiveness, tolerability and cost-effectiveness of drug therapy are a major considerations. A number of drug therapies are licensed for the treatment of epilepsy in adults, although many are limited to specific types of epilepsy and therapy regimens. However, at present, there does not appear to be a uniform approach to the selection or sequence of AED therapy.

Aims of the review

To examine the clinical effectiveness, tolerability and cost-effectiveness of gabapentin (GBP), lamotrigine (LTG), levetiracetam (LEV), oxcarbazepine (OXC), tiagabine (TGB), topiramate (TPM) and vigabatrin (VGB) for epilepsy in adults.

Methods

Results

Conclusions

There was little good-quality evidence from clinical trials to support the use of newer monotherapy or adjunctive therapy AEDs over older drugs, or to support the use of one newer AED in preference to another. In general, data relating to clinical effectiveness, safety and tolerability failed to demonstrate consistent and statistically significant differences between the drugs. The exception was comparisons between newer adjunctive AEDs and placebo, where significant differences favoured newer AEDs. However, trials often had relatively short-term treatment durations and often failed to limit recruitment to either partial or generalised onset seizures, thus limiting the applicability of the data.

Text removed due to reference to commercial-in-confidence data.

In addition, newer AEDs, used as monotherapy, may be cost-effective for the treatment of patients who have experienced adverse events with older AEDs, who have failed to respond to the older drugs, or where such drugs are contraindicated. The integrated economic analysis also suggested that newer AEDs used as adjunctive therapy may be cost-effective compared with the continuing current treatment alone given a threshold willingness to pay per QALY of about £20,000.

Recommendations for research

There is a need for the following:

• more direct comparisons of newer versus newer and newer, versus older AEDs within clinical trials, considering different treatment sequences within both monotherapy and adjunctive therapy;
• good-quality trials with appropriate designs, ideally adopting the International League Against Epilepsy guidelines on the design of trials, particularly with regard to length of follow-up;
• trials specifically to recruit patients with either partial or generalised seizures;
• more good-quality trials to investigate effectiveness and cost-effectiveness in patients with generalised onset seizures;
• more good-quality trials to investigate effectiveness in specific populations of epilepsy patients;
• studies evaluating cognitive outcomes to use more stringent testing protocols and to adopt a more consistent approach in assessing outcomes;
• further research to assess quality of life within trials of epilepsy therapy, adopting any measure shown to have validity in the assessment of epilepsy patients, but also using preference-based measures of outcomes that generate appropriate utilities for cost-effectiveness analysis; future RCTs to be adequately reported according to CONSORT guidelines; and
• observational data to provide information on the use of AEDs in actual practice, including details of treatment sequences and doses.

Publication

• Wilby J, Kainth A, Hawkins N, Epstein D, McIntosh H, McDaid C, et al. Clinical effectiveness, tolerability and cost-effectiveness of newer drugs for epilepsy in adults: a systematic review and economic evaluation. Health Technol Assess 2005;9(15). [PubMed: 15842952]

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