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Abstract Background The prescription of psychotropic medication is rising in Europe along the last decade. Exploring consumption patterns in pre-pandemic times in Portugal, as well as relevant socio-demographic determinants, can help establish comparisons with worldwide patterns and support public health policies for mental health. Methods Descriptive, non-comparative cohort study, comprising full nationwide drug prescription records in Portugal along antidepressant, antipsychotic, and anxiolytic classes. Statistical analysis of prescription and consumption patterns according to reference dosages and guided by several criteria, including active substance, demographics, geography, associated medical specialty, and incurred costs. Results An increase of 29.6% and 34.7% in the consumption of antipsychotics and antidepressants between 2016 and 2019 is highlighted, reasonably accompanied by an increase of 37M Eur in total expenditure (>20M Eur in public copay) for these classes of drugs. Disparities in sociodemographic and geographical incidence are identified. Amongst other pivotal results, we further observed that 64% of psychotropic drug prescriptions are undertaken by general practitioners, while only 21% undertaken by neurological and psychiatric specialties. Conclusion Nationwide patterns of psychotropic drug prescription in Portugal reveal notable trends and determinants, establishing a reference point for cross-regional studies and being currently assessed at a national level to establish psychosocial initiatives and guidelines for the clinical practice and medical training. Novelty To our knowledge, first Portuguese psychopharmacoepidemiological study assessing: 1) economic correlates; 2) prescription patterns by medical specialty; 3) adherence rates and geographical determinants; 4) consumption patterns by active substance; and 5) systematic trends for the pre-pandemic period.