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Clinically Significant Drug Interactions with Newer Antidepressants

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Abstract

After the introduction of selective serotonin reuptake inhibitors (SSRIs), other newer antidepressants with different mechanisms of action have been introduced in clinical practice. Because antidepressants are commonly prescribed in combination with other medications used to treat co-morbid psychiatric or somatic disorders, they are likely to be involved in clinically significant drug interactions. This review examines the drug interaction profiles of the following newer antidepressants: escitalopram, venlafaxine, desvenlafaxine, duloxetine, milnacipran, mirtazapine, reboxetine, bupropion, agomelatine and vilazodone.

In general, by virtue of a more selective mechanism of action and receptor profile, newer antidepressants carry a relatively low risk for pharmacodynamic drug interactions, at least as compared with first-generation antidepressants, i.e. monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs). On the other hand, they are susceptible to pharmacokinetic drug interactions. All new antidepressants are extensively metabolized in the liver by cytochrome P450 (CYP) isoenzymes, and therefore may be the target of metabolically based drug interactions. Concomitant administration of inhibitors or inducers of the CYP isoenzymes involved in the biotransformation of specific antidepressants may cause changes in their plasma concentrations. However, due to their relatively wide margin of safety, the consequences of such kinetic modifications are usually not clinically relevant. Conversely, some newer antidepressants may cause pharmacokinetic interactions through their ability to inhibit specific CYPs. With regard to this, duloxetine and bupropion are moderate inhibitors of CYP2D6. Therefore, potentially harmful drug interactions may occur when they are coadministered with substrates of these isoforms, especially compounds with a narrow therapeutic index. The other new antidepressants are only weak inhibitors or are not inhibitors of CYP isoforms at usual therapeutic concentrations and are not expected to affect the disposition of concomitantly administered medications.

Although drug interactions with newer antidepressants are potentially, but rarely, clinically significant, the use of antidepressants with a more favourable drug interaction profile is advisable. Knowledge of the interaction potential of individual antidepressants is essential for safe prescribing and may help clinicians to predict and eventually avoid certain drug combinations.

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Acknowledgements

The preparation of this review was not supported by any external funding. Prof. Spina has previously received honoraria for speaking and consultation from AstraZeneca, Boehringer-Ingelheim, Eli Lilly, Janssen, Lundbeck and Pfizer. The other authors have no conflicts of interest to declare.

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Authors and Affiliations

  1. Section of Pharmacology, Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Policlinico Universitario, Via Consolare Valeria, 98125, Messina, Italy

    Edoardo Spina & Gianluca Trifirò

  2. IRCCS Centro Neurolesi “Bonino-Pulejo”, Messina, Italy

    Edoardo Spina & Gianluca Trifirò

  3. Department of Formative Processes, University of Catania, Catania, Italy

    Filippo Caraci

  4. Department of Clinical and Molecular Biomedicine, Section of Pharmacology and Biochemistry, University of Catania, Catania, Italy

    Filippo Caraci

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  1. Edoardo Spina
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  2. Gianluca Trifirò
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Correspondence to Edoardo Spina.

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Spina, E., Trifirò, G. & Caraci, F. Clinically Significant Drug Interactions with Newer Antidepressants. CNS Drugs 26, 39–67 (2012). https://doi.org/10.2165/11594710-000000000-00000

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