Regulatory mechanisms for controlling the prices of medicines are used in most Member States of the European Union. They are one of elements government strategies to limit public expenditure on health care. The system of regulating the prices of medicines in the Republic of Croatia includes prescription medicines. HALMED sets the maximum permitted wholesale price of a medicine and exceptionally higher than the maximum permitted wholesale price of the medicine. The purpose of the study was to analyze the characteristics of the maximum permitted wholesale price of a medicine for medicines that act on the nervous system. The first aim is to test the hypothesis which assumes that the determination of the maximum permitted wholesale price of a medicine achieves a reduction of the price for some of the medicines covered by the procedure in 2020. The second aim is to test the hypothesis which assumes that the price reduction on the HZZO list of medicines is a consequence of the reduction of the maximum permitted wholesale price of the medicine from the annual price calculation in 2020. The research methods are based on statistical analysis of data on the mentioned group of medicines in the Microsoft Excel program, version 2016. As a source of numerical data, calculations of the maximum permitted wholesale prices of medicines according to the unified ordinance for 2019 and 2020, provided by HALMED and HZZO, were used. Literature data include scientific articles, books and websites on the topic of external reference pricing system in the Republic of Croatia and in the world, general system for regulation of drug prices in the health system, ATK classification of drugs, drugs acting on the nervous system, etc. The research results indicate significant impact of the maximum permitted wholesale price of a medicine on the reduction of the prices of drugs with an effect on the nervous system which are on and aren't on the HZZO list. In conclusion, an external reference pricing system may not lead to a satisfactory result in lowering drug prices or expanding drug affordability to end-users in the long run if regulatory frameworks are not designed to increase public expenditures and access to effective therapies for all patients without adversely affecting the health system.