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Objective: To assess the cost-effectiveness of sodium oxybate plus antidepressants and stimulants compared with the current standard treatment for narcolepsy with cataplexy in the UK. Methods: We developed a Markov model to assess the costs and benefits of sodium oxybate plus antidepressants and stimulants or current standard treatment based on their effects on the quality of life of patients. The main outcome was the incremental cost-effectiveness ratio (ICER) in terms of costs per additional qualityadjusted life year (QALY) gained over 5 years of treatment. One-way, multi-way and probabilistic sensitivity analyses were conducted to explore the impact of uncertainties on the findings. Results: The cost-effectiveness of sodium oxybate plus antidepressants and stimulants were very sensitive to the costs of sodium oxybate (price and dose) and differences in utilities between responders and non-responders. With current clinical evidence, it is recognised that measure of improvement in utilities used in the current model may be an underestimation of the reality. Conclusions: Our analysis suggests that, at the current UK list price, sodium oxybate would not represent good value for money for the NHS. This is unfortunate, since it appears that sodium oxybate is likely to benefit some patients in the management of these two conditions which affect about 0.03% of the UK population.