Rationale Management of anxiety, delirium, and agitation cannot be neglected in coronavirus disease . Antipsychotics are usually used for the pharmacological management of delirium, and confusion and behavioral disturbances. The concurrent use of treatments for COVID-19 and antipsychotics should consider eventual drug-drug interactions Objective To systematically review evidence-based available on drug-drug interactions between COVID-19 treatments and antipsychotics. Evidence review Three databases were consulted: Lexicomp® Drug Interactions, Micromedex® Solutions Drugs Interactions, and Liverpool© Drug Interaction Group for COVID-19 therapies. To acquire more information on QT prolongation and Torsade de Pointes (TdP), the CredibleMeds® QTDrugs List was searched. The authors made a recommendation agreed to by consensus. Additionally, a systematic review of drug-drug interactions between antipsychotics and COVID-19 treatment was conducted. Results The main interactions between COVID-19 drugs and antipsychotics are the risk of QT-prolongation and TdP, and cytochromes P450 interactions. Remdesivir, baricinitib, and anakinra can be used concomitantly with antipsychotics without risk of drug-drug interaction (except for hematological risk with clozapine and baricinitib). Favipiravir only needs caution with chlorpromazine and quetiapine. Tocilizumab is rather safe to use in combination with antipsychotics. The most demanding COVID-19 treatments for coadministration with antipsychotics are chloroquine, hydroxychloroquine, azithromycin, and lopinavir/ritonavir because of the risk of QT prolongation and TdP and cytochromes interactions. The systematic review provides highly probable drug interaction between lopinavir/ ritonavir plus quetiapine and ritonavir/indinavir plus risperidone. Conclusions Clinicians prescribing antipsychotics should be aware of the likely risk of drug-drug interaction with COVID-19 medication and may benefit from taking into account present recommendations of use to preserve patient safety K e y w o r d s C O V I D -1 9 . D r u g -d r u g i n t e r a c t i o n . Psychopharmacotherapy . Side effects * Benedicto Crespo-Facorro

Introduction The SARS-CoV-2 pandemic with psychiatric comorbidities leads to a scenario in which the use of psychotropic drugs may be required. This requires the support of evidence-based medicine to take into account possible interactions between antidepressants, mood stabilizers, benzodiazepines, and coronavirus infection treatments. Methods Three databases were consulted: (a) Lexicomp Drug Interactions, (b) Micromedex Solutions Drugs Interactions, (c)Liverpool Drug Interaction Group for COVID-19 therapies. The CredibleMeds QTDrugs List was also queried. Hydroxychloroquine, chloroquine, azithromycin, lopinavir-ritonavir, remdesivir, favipiravir, tocilizumab, baricitinib, anakinra, and dexamethasone – drugs used for SARS-CoV-2 – were analyzed, and consensus recommendations are made. Results The potential interactions of agomelatine, desvenlafaxine, duloxetine, milnacipran, and vortioxetine with COVID-19 treatments shall be considered less risky. Antidepressant interactions with hydroxychloroquine, chloroquine, and azithromycin enhance the risk of QT prolongation, and ECG monitoring is advised for most antidepressants. Antidepressants with lopinavir/ritonavir involve multiple CYP enzyme interactions (except with milnacipran). Gabapentin, oxcarbazepine, pregabalin, topiramate, and zonisamide are safe treatment options that have no significant interactions with COVID-19 treatments. Lithium is contraindicated with hydroxychloroquine, chloroquine, and azithromycin. Precaution should be taken in using valproic acid with lopinavir-ritonavir. The use of benzodiazepines does not present a risk of drug interaction with COVID-19 treatments, except lopinavir/ritonavir. Conclusions Clinicians prescribing antidepressants, mood stabilizers/anticonvulsants, and benzodiazepines, should be aware of the probable risk of drug-drug interaction with COVID-19 medications and may benefit from heeding these recommendations for use to ensure patient safety.