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Background Agitation is a common challenging behaviour in dementia with a negative influence on patient's quality of life and a high caregiver burden. Treatment is often difficult. Current guidelines recommend restrictive use of psychotropic drug treatment, but guideline recommendations do not always suffice. Objective To explore how physicians decide on psychotropic drug treatment for agitated behaviour in dementia when the guideline prescribing recommendations are not sufficient. Methods We conducted five online focus groups with a total of 22 elderly care physicians, five geriatricians and four old-age psychiatrists, in The Netherlands. The focus groups were thematically analysed. Results We identified five main themes. Transcending these themes, in each of the focus groups physicians stated that there is 'not one size that fits all'. The five themes reflect physicians' considerations when deciding on psychotropic drug treatment outside the guideline prescribing recommendations for agitated behaviour in dementia: (1) 'reanalysis of problem and cause', (2) 'hypothesis of underlying cause and treatment goal', (3) 'considerations regarding drug choice', (4) 'trial and error' and (5) 'last resort: sedation'. Conclusion When guideline prescribing recommendations do not suffice, physicians start with reanalysing potential underlying causes. They try to substantiate and justify medication choices as best as they can with a hypothesis of underlying causes or treatment goal, using other guidelines, and applying personalised psychotropic drug treatment. [ABSTRACT FROM AUTHOR]