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

Abstract

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.

Competing Interest Statement

Potential conflicts of Interest: Plasencia-Garcia B.O., has received honoraria for consulting/advisory boards from Otsuka Pharmaceuticals, Lundbeck and Janssen Johnson & Johnson and lecture honoraria from Otsuka Pharmaceuticals, Lundbeck, Janssen Johnson & Johnson, Angelini and Pfizer. Crespo-Facorro B., has received honoraria for consulting/advisory boards from Otsuka Pharmaceuticals, Takeda, Angellini and lecture honoraria from Janssen Johnson & Johnson, Lundbeck, Roche and Otsuka Pharmaceutical. The other authors declare that they have no known conflicts of interest. No pharmaceutical industry or institutional sponsors participated in the study design, data collection, analysis, and interpretation of the results

Clinical Trial

CRD42020183202 (PROSPERO)

Funding Statement

No external funding was received

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

No apply to the study

All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.

Yes

Data Availability

Data is available in the article and supplementary material

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