Drug–drug interactions and clinical considerations with co-administration of antiretrovirals and psychotropic drugs

Abstract

Psychotropic medications are frequently co-prescribed with antiretroviral therapy (ART), owing to a high prevalence of psychiatric illness within the population living with HIV, as well as a 7-fold increased risk of HIV infection among patients with psychiatric illness. While ART has been notoriously associated with a multitude of pharmacokinetic drug interactions involving the cytochrome P450 enzyme system, the magnitude and clinical impact of these interactions with psychotropics may range from negligible effects on plasma concentrations to life-threatening torsades de pointes or respiratory depression. This comprehensive review summarizes the currently available information regarding drug–drug interactions between antiretrovirals and pharmacologic agents utilized in the treatment of psychiatric disorders—antidepressants, stimulants, antipsychotics, anxiolytics, mood stabilizers, and treatments for opioid use disorder and alcohol use disorder—and provides recommendations for their management. Additionally, overlapping toxicities between antiretrovirals and the psychotropic classes are highlighted. Knowledge of the interaction and adverse effect potential of specific antiretrovirals and psychotropics will allow clinicians to make informed prescribing decisions to better promote the health and wellness of this high-risk population.

Psychopharmacology of COVID-19

“…Protease inhibitors are extensively metabolized by the cytochrome P450 system and have been shown to interact with many drugs, including psychotropics. 53 The use of ritonavir may lead to increased concentrations of coadministered drugs that are CYP3A4 or CYP2D6 substrates or decreased concentrations of CYP1A2 or CYP2B6 substrates, many of which are psychotropics.…”

“…Owing to CYP450 enzyme or glucuronidation-inducing effects, ritonavir-boosted protease inhibitors also have been shown to lower concentrations of some psychotropics (e.g., bupropion, methadone, lamotrigine, and olanzapine), thus leading to increased dose requirements for these medications. 53 As most psychotropics are substrates for CYP isoenzymes, there are many additional theoretical interactions, but the clinical significance varies by agent. Clinicians should assess each potential interaction individually by reviewing available literature and manufacturer's prescribing information.…”

Anti-HIV and Anti-Hepatitis C Virus Drugs Inhibit P-Glycoprotein Efflux Activity in Caco-2 Cells and Precision-Cut Rat and Human Intestinal Slices

“…Up to 10% of HIV-infected patients refuse to continue antiretroviral therapy because of its side effects (8,(10)(11)(12). Intolerability is frequently due to drug-drug interactions (DDIs), which increase the plasma concentrations of antivirals or coadministered medications (8,9,(13)(14)(15)(16)(17)(18)(19)(20). The molecular mechanisms responsible for this increased bioavailability are often unclear.…”

Drug Interactions of Psychiatric and COVID-19 Medications

“…Clinically significant interactions between mirtazapine and ritonavir-boosted lopinavir have not been reported. However, it is suggested that the lowest efficient dose of mirtazapine be used when it is co-administered with CYP3A4 inhibitors ( Goodlet, Zmarlicka, & Peckham, 2019 ). No interaction has been found between mirtazapine and hydroxychloroquine, chloroquine, ribavirin, and interferons.…”