Drug-Drug interactions between COVID-19 treatments and antipsychotics drugs: integrated evidence from 4 databases and a systematic review

Plasencia-Garcia, B. O.; Rodriguez-Menendez, G.; Rico-Rangel, M. I.; Rubio-Garcia, A.; Torello-Iserte, J.; Crespo-Facorro, B.

Relevance: Management of symptoms like anxiety, delirium and agitation cannot be neglected in COVID-19 patients. Antipsychotics are usually used for the pharmacological management of delirium, and confusion and behavioral disturbances. The selection of concomitant COVID-19 medications and antipsychotics should be evidence-based and closely monitored Objective: To systematically review evidence-based available on drug-drug interactions between COVID-19 treatments and antipsychotics. Evidence Review: Three databases were consulted: (a) Lexicomp Drug Interactions, (b) Micromedex Solutions Drugs Interactions, (c) Liverpool Drug Interaction Group for COVID-19 therapies. To acquire more information on QT prolongation and TdP, the CredibleMeds QTDrugs List was searched. Based on the information collected, the authors made a recommendation agreed to by consensus. In addition, a systematic review was conducted to find the clinical outcomes of drug-drug interactions between COVID-19 treatments and antipsychotics Results: The main interaction between COVID-19 drugs and antipsychotics are the risk of QT prolongation and TdP, and CYP interactions. Remdesivir, favipiravir, baricinitib, and anakinra can be used concomitantly with antipsychotics with no risk of drug-drug interaction (except for hematological risk with clozapine and baricinitib). Tocilizumab is rather safe to use in combination with antipsychotics, although it can restore the activity of CYP3A4 and therefore its substrate metabolism may increase. The most demanding COVID-19 treatments for co-administration with antipsychotics are chloroquine, hydroxychloroquine, azithromycin (all prolong QT interval) and lopinavir / ritonavir (CYP interaction and risk of QT prolongation). Conclusions: We urge to development of evidence-based guidelines that can help clinicians decide the safest treatment combination and monitoring necessary for each particular patient. The selection of concomitant COVID-19 medications and antipsychotics should be evidence-based and closely monitored.