Drug Interactions of Psychiatric and COVID-19 Medications

Abstract

Coronavirus disease 2019 (COVID-19) has become a pandemic with 1771514 cases identified in the world and 70029 cases in Iran until April 12, 2020. The co-prescription of psychotropics with COVID-19 medication is not uncommon. Healthcare providers should be familiar with many Potential Drug-Drug Interactions (DDIs) between COVID-19 therapeutic agents and psychotropic drugs based on cytochrome P450 metabolism. This review comprehensively summarizes the current literature on DDIs between antiretroviral drugs and chloroquine/hydroxychloroquine, and psychotropics, including antidepressants, antipsychotics, mood stabilizers, and anxiolytics. Methods: Medical databases, including Google Scholar, PubMed, Web of Science, and Scopus were searched to identify studies in English with keywords related to psychiatric disorders, medications used in the treatment of psychiatric disorders and COVID-19 medications. Results: There is a great potential for DDIs between psychiatric and COVID-19 medications ranging from interactions that are not clinically apparent (minor) to those that produce lifethreatening adverse drug reactions, or loss of treatment efficacy. The majority of interactions are pharmacokinetic interactions via the cytochrome P450 enzyme system. Conclusion: DDIs are a major concern in the comorbidity of psychiatric disorders and COVID-19 infection resulting in the alteration of expected therapeutic outcomes. The risk of toxicity or lack of efficacy may occur due to a higher or lower plasma concentration of medications. However, psychiatric medication can be safely used in combination with COVID-19 pharmacotherapy with either a wise selection of medication with the least possibility of interaction or careful patient monitoring and management.

Depressive Disorders and Incidence of COVID-19: Is There a Correlation and Management Interference?

“…Clinically significant interactions between mirtazapine and ritonavir boosted lopinavir have not been reported. No interaction has been found between mirtazapine and Hydroxychloroquine, chloroquine, ribavirin and interferons [32].…”

“…In a clinical trial phase 1 performed on 12 subjects administration of ritonavir and lopinavir (400 mg/100 mg two times daily) resulted in 57% reduction in bupropion AUC. In another study, the results showed that high dose (600 mg two times daily) and low dose (100 mg twice daily) of ritonavir resulted in 67% and 22% lowering in bupropion serum concentrations, respectively [32].…”

“…Fluoxetine and Nor-fluoxetine (its active metabolite) inhibit CYP2D6 (strong), CYP2C9 (moderate), CYP2C19 (weak to moderate), CYP3A4 (weak to moderate), and CYP1A2 (weak). Thus, Fluoxetine and its metabolites increase the area under the curve (AUC) of ritonavir by up to 19% through inhibiting CYP2D6 and CYP3A4 (especially CYP2D6) without significant change in other kinetic parameters of ritonavir [32]. Fluoxetine as a CYP2D6 inhibitor (strong) may decrease the metabolism of CYP2D6 substrates like chloroquine and Hydroxychloroquine [32].…”

“…Its protein binding is 95% and can inhibit the CYP2D6 enzyme. Manon et al, reported that co-administration of paroxetine (20 mg/d) with fosamprenavir and ritonavir (700 mg/100 mg twice per day) for 10 days causes a decrease of paroxetine levels by 55% compared to its administration alone because of protein binding displacement [32].…”

“…Medications like Citalopram / Escitalopram and Chloroquine / Hydroxychloroquine are known for causing cardiac complications (such as QTc prolongation),where the possibility of this complication seemed additive and can be aggravated by old age, cardiac disease, electrolyte disturbances (hypokalemia, hypomagnesemia), and bradycardia [32]. Sertraline may enhance the risk of hypoglycemia when co-administered with agents that have blood glucose effects like chloroquine/Hydroxychloroquine [32].…”