Background Patients with mental illnesses are at increased risk of cardiovascular disease-related mortality. Antihypertensive drugs are used particularly for the prophylaxis and treatment of cardiovascular diseases. In combination with psychiatric medication there is a potential for interaction, which can impair the achievement of therapeutic goals. Objective The prescription behavior for antihypertensive drugs in psychiatric clinics and practices in German-speaking countries as well as the interaction potential with psychotropic drugs were investigated. Methods The AGATE "index day" database, which anonymously stores patient data on age, sex, psychiatric main diagnosis as well as the prescribed commercial preparations collected in AGATE institutions (hospitals and community practitioners), was analyzed. The possible interactions were analyzed with PSIAC. Results Between 1 January 2012 and 31 December 2016, 27% of all 21,980 patients recorded had a prescription for at least 1 antihypertensive drug, rising to 72% among patients over 80 years old. Of the patients treated with antihypertensive drugs, 48% received antihypertensive monotherapy. The importance of antihypertensive drug combination treatment increased with age. A median of 7 active substances were prescribed to the patients which mathematically results in 21 interactions. The simultaneous administration of psychotropic and antihypertensive drugs can result in an increased risk of hypotension, insufficient blood pressure reduction or QTc prolongation. Conclusion Antihypertensive drugs are important in the treatment of psychiatric patients. An interaction test should be performed if pharmacotherapy is to be supplemented or changed. Where appropriate, measures to improve drug treatment safety should be considered.