Background: Drug poisoning is considered as one of the main principal reasons for acute care hospitals admissions, and it places a significant burden on emergency medical services resources. The aim of this study is to examine the trend of hospital admission due to poisoning by psychotropic drugs and prescrip-tions of psychotropic medications in England and Wales in the past 21 years.Method: Hospital admission data from the Hospital Episode Statistics database in England and the Patient Episode Database in Wales were used in this ecological study. For the period from April 1999 to March 2020, hospital admissions data relating to poisoning by, classified by adverse effects of, and underdosing of psychiatric medications were extracted. Data on CNS drug prescriptions was collected for the time per-iod 2004-2020.Results: During the study period, hospital admission rate increased by19.9% [from 39.94 (95% CI 39.40- 40.48) in 1999 to 47.90 (95% CI 47.34-48.45) in 2020 per 100,000 persons, trend test, p < 0.05]. The most common reason of poisoning by psychotropic drugs that lead to hospital admissions was unspecified poi-soning by antidepressants (accidental (unintentional), intentional self-harm, assault, as adverse effect, and under-dosing), which accounted for 48.9% of the total number of admissions. CNS medications prescription rates increased by 56.4% [from 247629.78 (95% CI 247593.18-247666.39) in 2004 to 387372.48 (95% CI 387333.41-387411.55) in 2020 prescriptions per 100,000 persons, trend test, p < 0.001]. The most com-monly prescribed CNS medications prescriptions were analgesics, antidepressant, antiepileptic, and hyp-notics and anxiolytics, which accounted for: 35.0%, 28.7%, 10.0%, and 9.5%, respectively. During the study. period between 2004 and 2020, the overall medications prescribing rate showed to be very strongly and positively correlating the hospital admissions rate with the overall poisoning by psychotropic drugs (r = 0.799; p <= 0.001).Conclusion: Over the last two decades, there has been a parallel increase in the hospitalization rate for psy-chotropic drug poisoning and the prescription rate for CNS medications. Future research should focus on identifying high-risk populations who are more prone to psychotropic drug poisoning.(c) 2022 The Authors. Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).