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Cited by 95Pharmacogenetics and Drug MetabolismSchizophrenia research and treatmentPharmaceutical Practices and Patient Outcomes

Clinically Significant Drug Interactions with Atypical Antipsychotics

Kennedy, William Klugh, Jann, Michael W., Kutscher, Eric C.·2013·CNS Drugs
DOI 10.1007/s40263-013-0114-6
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Abstract

Atypical antipsychotics [also known as second-generation antipsychotics (SGAs)] have become a mainstay therapeutic treatment intervention for patients with schizophrenia, bipolar disorders and other psychotic conditions. These agents are commonly used with other medications--most notably, antidepressants and antiepileptic drugs. Drug interactions can take place by various pharmacokinetic, pharmacodynamic and pharmaceutical mechanisms. The pharmacokinetic profile of each SGA, especially with phase I and phase II metabolism, can allow for potentially significant drug interactions. Pharmacodynamic interactions arise when agents have comparable receptor site activity, which can lead to additive or competitive effects without alterations in measured plasma drug concentrations. Additionally, the role of drug transporters in drug interactions continues to evolve and may effect both pharmacokinetic and pharmacodynamic interactions. Pharmaceutical interactions occur when physical incompatibilities take place between agents prior to drug absorption. Approximate therapeutic plasma concentration ranges have been suggested for a number of SGAs. Drug interactions that markedly increase or decrease the concentrations of these agents beyond their ranges can lead to adverse events or diminished clinical efficacy. Most clinically significant drug interactions with SGAs occur via the cytochrome P450 (CYP) system. Many but not all drug interactions with SGAs are identified during drug discovery and pre-clinical development by employing a series of standardized in vitro and in vivo studies with known CYP inducers and inhibitors. Later therapeutic drug monitoring programmes, clinical studies and case reports offer methods to identify additional clinically significant drug interactions. Some commonly co-administered drugs with a significant potential for drug-drug interactions with selected SGAs include some SSRIs. Antiepileptic mood stabilizers such as carbamazepine and valproate, as well as other antiepileptic drugs such as phenobarbital and phenytoin, may decrease plasma SGA concentrations. Some anti-infective agents such as protease inhibitors and fluoroquinolones are of concern as well. Two additional important factors that influence drug interactions with SGAs are dose and time dependence. Smoking is very common among psychiatric patients and can induce CYP1A2 enzymes, thereby lowering expected plasma levels of certain SGAs. It is recommended that ziprasidone and lurasidone are taken with food to promote drug absorption, otherwise their bioavailability can be reduced. Clinicians must be aware of the variety of factors that can increase the likelihood of clinically significant drug interactions with SGAs, and must carefully monitor patients to maximize treatment efficacy while minimizing adverse events.

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  • Several factors can influence the rate and extent of absorption of oral antipsychotics, including drug dissolution, drug solubility, susceptibility to enzymatic reactions, gastric pH, drug-drug interactions, and food-drug interactions.

    “Several factors can influence the rate and extent of absorption of oral antipsychotics, including drug dissolution, drug solubility, susceptibility to enzymatic reactions, gastric pH, drug–drug interactions, and food–drug interactions [22–24].”

    From Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview (2021) · cites this paper as [23]

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Authors
Kennedy, W. K., Jann, M. W., & Kutscher, E. C.
Affiliations
  • Mercer University (US)
  • University of North Texas System (US)
  • South Dakota State University (US)
Corresponding author
Jann, Michael W.
ORCID
Venue
CNS Drugs
Publisher
Springer Science and Business Media LLC
Published
2013-10-30
Volume
27
Issue
12
Pages
1021-1048
ISSN
  • 1172-7047 (ISSN-L)
  • 1179-1934
DOI
10.1007/s40263-013-0114-6
OpenAlex
W2086036313
Cited by
95
References
155
Citations by year
2026: 3 · 2025: 4 · 2024: 5 · 2023: 7 · 2022: 4 · 2021: 12 · 2020: 9 · 2019: 8 · 2018: 11 · 2017: 8 · 2016: 11 · 2015: 5 · 2014: 8
FWCI
1.31
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • CNS Drugs (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
Keywords
atypical antipsychotics, drug-drug interactions, cytochrome P450, pharmacokinetic interactions, pharmacodynamic interactions, drug transporters, antidepressants, antiepileptic drugs, selective serotonin reuptake inhibitors, carbamazepine, valproic acid, protease inhibitors, fluoroquinolones, therapeutic drug monitoring, ziprasidone, lurasidone, schizophrenia, bipolar disorder
MeSH terms
Animals, Anticonvulsants, Antidepressive Agents, Clinical Trials as Topic, Drug Interactions, Humans, Protein Binding, Psychotic Disorders, Antipsychotic Agents, Drug Monitoring, Selective Serotonin Reuptake Inhibitors

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