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Different types of rewards are applied in persuasive games to encourage play persistence of its users and facilitate the achievement of desired real-world goals, such as behavioral change. Persuasive games have successfully been applied in mental healthcare and may hold potential for different types of patients. However, we question to what extent game-based rewards are suitable in a persuasive game design for a substance dependence therapy context, as people with substance-related disorders show decreased sensitivity to natural rewards, which may result in different responses to commonly applied game rewards compared to people without substance use disorders. In a within-subject experiment with 20 substance dependent and 25 non-dependent participants, we examined whether play persistence and reward evaluation differed between the two groups. Results showed that in contrast to our expectations, substance dependent participants were more motivated by the types of rewards compared to non-substance dependent participants. Participants evaluated monetary rewards more positively than playing for virtual points or social rewards. We conclude this paper with design implications of game-based rewards in persuasive games for mental healthcare. [ABSTRACT FROM AUTHOR]