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Objectives Laxatives are among the most prescribed medications to nursing home (NH) patients, and we evaluated the hypothesis that laxative agents could be prescribed as a result of a prescribing cascade. The aims of the study are (1) to investigate the use of laxative drugs in a large sample of Italian NHs and (2) to assess the relationship between medications that can induce constipation and laxative use. Design Retrospective cross-sectional multicenter study. Setting and Participants Individuals living in long-term care NHs. Methods Study conducted in a sample of Italian long-term care NHs distributed throughout the country. Information on drug prescriptions, diseases and sociodemographic characteristics collected 4 times during 2018 and 2019. Results Among the 2602 patients recruited from 27 NHs (mean age ± standard deviation: 88.4 ± 8.5; women: 1994, 76.6%), 1248 were receiving laxatives (48%). Parkinson disease, cerebrovascular disease, and hemiplegia were associated with laxative prescription, and diabetes was associated with a decrease. Benzodiazepines, anti-Parkinson dopaminergic agents, and antidepressants (tricyclic antidepressants and mirtazapine) were associated with laxative treatment in univariate and adjusted models. Tricyclic antidepressants users were 3 times more likely to be taking laxatives than nonusers (odds ratio 2.98, 95% confidence interval 1.31-6.77, P = .0093). A larger number of drugs that can induce constipation was associated with laxative use (P = .0003). In all, 2002 individuals had at least 2 different prescription times: from the first to the last visit laxative use rose from 46.1% to 49.9%. Time of stay was also associated with laxative use (P = .016). Conclusions and Implications Laxatives are among the most prescribed medications in Italian NHs. Medications that can induce constipation, such as antidepressants, anti-Parkinson dopaminergic agents, and benzodiazepines, are often used together with laxatives, and combinations of these drugs further increase the use of laxatives. Optimizing the prescription of psychotropic drugs could help reduce the “prescribing cascade” with laxatives. The length of stay in NHs is often proportional to laxative use and chronic treatment is very common.