Tricyclic antidepressants inhibit Candida albicans growth and biofilm formation
Abstract
Candida albicans is a commensal yeast of the human body, able to form biofilms on solid surfaces such as implanted medical devices, and contributes to nosocomial infections. Biofilms have the capacity to resist higher levels of antifungals compared with planktonic cells, and can develop tolerance to commonly used treatments. The necessity to overcome acquired drug resistance and identify new active molecules with low toxicity is a significant problem. It has been reported that some antidepressants have antibacterial properties, but little is known regarding the effect of these drugs on fungi. This study demonstrated the capacity of three tricyclic antidepressants (doxepin, imipramine and nortriptyline) to inhibit the growth and biofilm formation of Candida spp. The antimicrobial potential of the drugs was assessed by studying gene expression, hyphae formation, biofilm growth and maturation. Their negative impact on the growth of C. albicans and other Candida spp. is shown in vitro and with the hepatic S9 system, which is preliminary to any in-vivo test. This study found that the antidepressants considered can inhibit not only hyphae and biofilm formation, but also kill cells in a mature biofilm. Moreover, cell lysis by nortriptyline was observed, along with its synergistic activity with amphotericin B. These findings suggest that tricyclic antidepressants, particularly nortriptyline, should be studied further in drug repositioning programmes to assess their antimycotic capacity in full.
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Biofilms act as protective barriers, significantly enhancing fungal resistance by shielding Candida species from conventional antifungal agents.
“Biofilms act as protective barriers, significantly enhancing fungal resistance by shielding Candida species from conventional antifungal agents [44, 45].”
From Statins as Antifungal Agents: A Review on Drug Repurposing and Nanotechnology-Driven Delivery Strategies (2025) · cites this paper as [44]
The antipsychotic phenothiazine and the antidepressant nortriptyline have been reported to disrupt cell membranes.
“The antipsychotic phenothiazine and the antidepressant nortriptyline have also been reported to disrupt cell membranes [72,104,105].”
From Antimicrobial Properties of Antidepressants and Antipsychotics—Possibilities and Implications (2021) · cites this paper as [72]
TCAs are active against Candida spp., where they inhibit hyphal formation, lyse cells, and kill them even in a mature biofilm.
“Works based on TCAs showed that this class of molecules was active against Candida spp., where they inhibited hyphal formation, lysed the cells, and killed them even in a mature biofilm [72,73].”
From Antimicrobial Properties of Antidepressants and Antipsychotics—Possibilities and Implications (2021) · cites this paper as [72]
The cell lysis induced by nortriptyline, local anesthetics, and antipsychotic phenothiazine is related to their amphiphilic structures and surfactant activity, which disturb cell membrane functionality.
“This phenomenon is related to their amphiphilic structures and their surfactant activity, which are able to disturb cell membrane functionality [11,13].”
From Known Antimicrobials Versus Nortriptyline in Candida albicans: Repositioning an Old Drug for New Targets (2020) · cites this paper as [11]
NOR has antimicrobial activity against Candida albicans.
“Another antidepressant with antimicrobial properties that was shown to be active against Candida albicans is NOR [11]”
From Known Antimicrobials Versus Nortriptyline in Candida albicans: Repositioning an Old Drug for New Targets (2020) · cites this paper as [11]
Nortriptyline inhibits biofilm and hyphae formation and efficiently kills cells in a mature C. albicans biofilm.
“Nortriptyline, a tricyclic antidepressant, was shown to have the capacity to inhibit biofilm and hyphae formation, along with the ability to efficiently kill cells in a mature biofilm.”
From Known Antimicrobials Versus Nortriptyline in Candida albicans: Repositioning an Old Drug for New Targets (2020) · cites this paper as [11]
Nortriptyline induces lysis of C. albicans cells.
“NOR induces lysis of cells [11]”
From Known Antimicrobials Versus Nortriptyline in Candida albicans: Repositioning an Old Drug for New Targets (2020) · cites this paper as [11]
The antimicrobial activity of NOR is synergic with other commercial drugs.
“the antimicrobial activity of NOR is synergic with other commercial drugs [11]”
From Known Antimicrobials Versus Nortriptyline in Candida albicans: Repositioning an Old Drug for New Targets (2020) · cites this paper as [11]
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References 20 · Cited by 31
- Authors
- Caldara, M., & Marmiroli, N.
- Affiliations
- University of Parma (IT)
- Corresponding author
- Caldara, Marina
- Venue
- International Journal of Antimicrobial Agents
- Publisher
- Elsevier BV
- Published
- 2018-10
- Volume
- 52
- Issue
- 4
- Pages
- 500-505
- ISSN
- 0924-8579 (ISSN-L)
- OpenAlex
- W2817933915
- Cited by
- 31
- References
- 20
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 5 · 2022: 6 · 2021: 3 · 2020: 4 · 2019: 4
- FWCI
- 2.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Antimicrobial Agents (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- tricyclic antidepressants, Candida albicans, biofilm formation, nortriptyline, doxepin, imipramine, antifungal activity, drug repurposing, amphotericin B synergy, nosocomial fungal infections, Candida
- MeSH terms
- Amphotericin B, Antidepressive Agents, Tricyclic, Antifungal Agents, Candida, Candida albicans, Doxepin, Drug Synergism, Fungal Proteins, Humans, Imipramine, Inactivation, Metabolic, Microsomes, Liver, Nortriptyline, Plankton, Gene Expression Regulation, Fungal, Biofilms, Hyphae, Candida glabrata, Drug Repositioning
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