Skip to main content Accessibility help
×
Home

Contents:

Information:

  • Access

Actions:

      • Send article to Kindle

        To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

        Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

        Find out more about the Kindle Personal Document Service.

        Commentary on: drug–drug interactions and clinical considerations with co-administration of antiretrovirals and psychotropic drugs
        Available formats
        ×

        Send article to Dropbox

        To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

        Commentary on: drug–drug interactions and clinical considerations with co-administration of antiretrovirals and psychotropic drugs
        Available formats
        ×

        Send article to Google Drive

        To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

        Commentary on: drug–drug interactions and clinical considerations with co-administration of antiretrovirals and psychotropic drugs
        Available formats
        ×
Export citation

Drs. Goodlet, Zmarlicka, and Peckham provide a thorough review of the psychopharmacologic drugs commonly used by people living with HIV/AIDS (PLWHA). In their comprehensive review, the authors highlight the currently available information about drug–drug interactions (DDIs) between antiretroviral therapy (ART) and psychotropic drugs used in the treatment of psychiatric disorders, the possible overlapping toxicities of both treatments, and provide recommendations for their management.Reference Goodlet, Zmarlicka and Peckham1

Regarding antipsychotic drugs, in the article, it is emphasized that there is a paucity of available data for clinical information about DDIs between ART and antipsychotics. Generally, many of the antipsychotics are metabolized via the CYP P450 system, in particular CYP 3A4 and CYP 2D6, and the potential for DDIs exists with concomitant administration of medications affecting these enzymes. However, in this review, the drug paliperidone is not mentioned. This treatment is an antipsychotic that could have many advantages in PLWHA.

Paliperidone, or 9-hydroxy-risperidone, is the major active metabolite of risperidone. It is an atypical antipsychotic which has significantly evidenced to be effective in improving psychotic symptoms in both oral and depot long-acting intramuscular formulations.Reference Kane, Canas and Kramer2, Reference Gopal, Hough and Xu3 Although there are no studies about the use of paliperidone among PLWHA, it is remarkable that recent consensus document on psychiatric aspect in adults with HIV infection recommends, specifically, the use of paliperidone for psychosis. This document specifies that paliperidone is the antipsychotic of choice due to its lower risk of extrapyramidal symptoms, metabolic side effects, and, mostly, pharmacokinetic interactions than other typical and atypical antipsychotics.Reference Polo, Blanch, Locutura and Arazo4

The metabolism of paliperidone in the liver is very limited; approximately 60% of the molecule is eliminated, unaltered, in the urine. The rest is eliminated in the form of urinary metabolites through dealkylation (4.6%), hydroxylation (3.8%), dehydrogenation (2.7%), and breakdown of the benzisoxazole nucleus (4.1%), and a small amount in feces. Due to its negligible hepatic biotransformation, paliperidone is unlikely to be involved in clinically significant metabolic interactions. Even though in vitro studies have demonstrated that isoenzymes CYP2D6 and CYP3A4 can intervene in paliperidone metabolism, there are no in vivo data available to confirm whether or not said isoenzymes play a significant metabolic role. For example, in a study of five healthy volunteers, after a single 1-mg dose of immediate-release paliperidone was taken orally, no metabolite was detected in the plasma. There are additional properties in terms of its lower protein binding and decreased inhibition of P-glycoprotein that lead to a decreased potential for DDIs.Reference Mora, Molina, Zubillaga, López-Muñoz and Álamo5, Reference Vermeir, Naessens and Remmerie6

Based on this data, it seems that paliperidone treatment, both the oral formulation and the depot long-acting intramuscular formulation, could be an effective, tolerable, and safety treatment in PLWHA taking ART. However, as with the other antipsychotics, caution and close monitoring of side effects are recommended when prescribing paliperidone treatment to HIV-infected patients due to the paucity of studies. Randomized controlled trials are needed to establish both efficacy and safety of antipsychotic drugs in the HIV population in order to improve and optimize psychiatric care.

Disclosures

Dr. Hernandez-Huerta reports travel, accommodations, and meeting expenses from Jannsen Pharmaceutical, Otsuka Pharmaceutical, and Lundbeck Pharmaceutical, outside the submitted work.

References

1.Goodlet, KJ, Zmarlicka, MT, Peckham, AM. Drug-drug interactions and clinical considerations with co-administration of antiretrovirals and psychotropic drugs. CNS Spectr. October 2018; 126. doi: 10.1017/S109285291800113X.
2.Kane, J, Canas, F, Kramer, M, et al. Treatment of schizophrenia with paliperidone extended-release tablets: A 6-week placebo-controlled trial. Schizophr Res. 2007; 90(1–3): 147161. doi: 10.1016/j.schres.2006.09.012.
3.Gopal, S, Hough, DW, Xu, H, et al. Efficacy and safety of paliperidone palmitate in adult patients with acutely symptomatic schizophrenia: A randomized, double-blind, placebo-controlled, dose-response study. Int Clin Psychopharmacol. 2010; 25(5): 247256. doi: 10.1097/YIC.0b013e32833948fa.
4.Polo, R, Blanch, J, Locutura, J, Arazo, P. Consensus document on psychiatric and psychological aspect in adults and children with HIV infection. Enferm Infecc Microbiol Clin. 2016; 34(1):53.e153.e14. doi: 10.1016/j.eimc.2015.07.018.
5.Mora, F, Molina, JD, Zubillaga, E, López-Muñoz, F, Álamo, C. CYP450 and its implications in the clinical use of antipsychotic drugs. Clin Exp Pharmacol. 2015; 5(176). doi: 10.4172/2161-1459.1000176.
6.Vermeir, M, Naessens, I, Remmerie, B, et al. Absorption, metabolism, and excretion of paliperidone, a new monoaminergic antagonist, in humans. Drug Metab Dispos. 2008; 36(4): 769779. doi: 10.1124/dmd.107.018275.