Dataset Information

Drug-drug interactions between psychiatric medications and MDMA or psilocybin: a systematic review.

ABSTRACT:

Rationale & objectives

± 3,4-Methylenedioxymethamphetamine (MDMA) and psilocybin are currently moving through the US Food and Drug Administration's phased drug development process for psychiatric treatment indications: posttraumatic stress disorder and depression, respectively. The current standard of care for these disorders involves treatment with psychiatric medications (e.g., selective serotonin reuptake inhibitors), so it will be important to understand drug-drug interactions between MDMA or psilocybin and psychiatric medications.

Methods

In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we queried the MEDLINE database via PubMed for publications of human studies in English spanning between the first synthesis of psilocybin (1958) and December 2020. We used 163 search terms containing 22 psychiatric medication classes, 135 specific psychiatric medications, and 6 terms describing MDMA or psilocybin.

Results

Forty publications were included in our systematic review: 26 reporting outcomes from randomized controlled studies with healthy adults, 3 epidemiologic studies, and 11 case reports. Publications of studies describe interactions between MDMA (N = 24) or psilocybin (N = 5) and medications from several psychiatric drug classes: adrenergic agents, antipsychotics, anxiolytics, mood stabilizers, NMDA antagonists, psychostimulants, and several classes of antidepressants. We focus our results on pharmacodynamic, physiological, and subjective outcomes of drug-drug interactions.

Conclusions

As MDMA and psilocybin continue to move through the FDA drug development process, this systematic review offers a compilation of existing research on psychiatric drug-drug interactions with MDMA or psilocybin.

SUBMITTER: Sarparast A

PROVIDER: S-EPMC9177763 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Drug-drug interactions between psychiatric medications and MDMA or psilocybin: a systematic review.

Sarparast Aryan A Thomas Kelan K Malcolm Benjamin B Stauffer Christopher S CS

Psychopharmacology 20220307 6

<h4>Rationale & objectives</h4> ± 3,4-Methylenedioxymethamphetamine (MDMA) and psilocybin are currently moving through the US Food and Drug Administration's phased drug development process for psychiatric treatment indications: posttraumatic stress disorder and depression, respectively. The current standard of care for these disorders involves treatment with psychiatric medications (e.g., selective serotonin reuptake inhibitors), so it will be important to understand drug-drug interactions betwe ...[more]

PMID: 35253070

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Project description:BackgroundGlucagon-like peptide 1 receptor agonists (GLP1RAs) are used in the treatment of diabetes and obesity. Their slowing effect of gastric emptying might change oral drug absorption, potentially affecting pharmacokinetics, particularly in the case of medications with a narrow therapeutic index.PurposeThe purpose of this systematic review is to summarize data on drug-drug interactions between GLP1RAs and oral drugs.Data sourcesThe PubMed and EMBASE databases were searched up to November, 1st 2023.Study selectionWe selected pharmacokinetic studies of any injectable GLP1RA given with an oral medication, and product prescribing sheets reporting data without access to the original study.Data extractionTwo authors independently extracted the data.Data synthesisTwenty-two reports and six prescribing sheets were included. Treatment with GLP1RAs resulted in unaffected or reduced Cmax and delayed tmax of drugs with high solubility and permeability (warfarin, contraceptive pills, acetaminophen), drugs with high solubility and low permeability (angiotensin converting enzyme inhibitors), drugs with low solubility and high permeability (statins) and drugs with low solubility and permeability (digoxin). However, the use of GLP1RAs did not exert clinically significant changes in the AUC or differences in clinically relevant endpoints.LimitationsThe major limitations of the studies that are included in this systematic review are the enrollment of healthy subjects and insufficient data in conditions that might affect pharmacokinetics (e.g., kidney dysfunction).ConclusionsTo conclude, reduced Cmax and delayed tmax of drugs co-administered with GLP1RAs are consistent with the known delayed gastric output by the latter. Nevertheless, the overall drug exposure was not considered clinically significant. Dose adjustments are probably not required for simultaneous use of GLP1RAs with oral medications. Still, results should be carefully generalized to cases of background kidney dysfunction or when using drugs with narrow therapeutic index. The study is registered in PROSPERO: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022332339 .

Project description:Background and objectiveSeveral review articles have been published discussing gastric acid-related drug-drug interactions (DDIs) mediated by coadministration of antacids, histamine H2 receptor antagonists, or proton pump inhibitors, but are not sufficiently comprehensive in capturing all documented DDIs with acid-reducing agents (ARAs) and tend to focus on gastric pH-dependent DDIs and/or basic drugs. Subsequently, several new drugs have been approved, and new information is available in the literature. The objective of this systematic review is to comprehensively identify oral medications that have clinically meaningful DDIs, including loss of efficacy or adverse effects, with gastric ARAs, and categorize these medications according to mechanism of interaction.MethodsAn indepth search of clinical data in the PDR3D: Reed Tech Navigator™ for Drug Labels, University of Washington Drug-Drug Interaction Database, DailyMed, Drugs@FDA.gov, and UpToDate®/Lexicomp® Drug and Drug Interaction screening tool was conducted from 1 June to 1 August 2018. The PDR3D, University of Washington Drug-Drug Interaction Database, and DailyMed were searched with terms associated with gastric acid and ARAs. Conflicting findings were further investigated using the UpToDate®/Lexicomp® screening tool. Clinical relevance was assessed on whether an intervention was needed, and prescribing information and/or literature supporting the DDI.ResultsThrough the search strategy, 121 medications were found to clinically meaningfully interact with ARAs. For 38 medications the mechanism of interaction with ARAs was identified as gastric pH dependent, and for 83 medications the interaction was found to be not gastric pH mediated, with mechanisms involving metabolic enzymes, transporters, chelation, and urine alkalization. Additionally, 109 medications were studied and did not have a clinically meaningful interaction with ARAs.ConclusionThis review may provide a resource to healthcare professionals in aiding the care of patients by increasing awareness of interactions with ARAs and may also identify and potentially aid in avoiding clinically relevant DDIs and preventing risk of treatment failure and/or adverse effects. Advances in non-clinical predictions of gastric pH-mediated DDIs may guide the need for a future clinical evaluation.

Dataset Information

Drug-drug interactions between psychiatric medications and MDMA or psilocybin: a systematic review.

Rationale & objectives

Methods

Results

Conclusions

Publications

Drug-drug interactions between psychiatric medications and MDMA or psilocybin: a systematic review.

Similar Datasets

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