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Drug Interactions and Polypharmacy

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Polypharmacy in Psychiatry Practice, Volume I

Abstract

Over the past 20 years the number of psychotropic medications has increased dramatically. As a result, the use of psychotropic polypharmacy has rapidly expanded. One outcome of psychotropic polypharmacy has been an increase in the number of drug interactions that occur in routine clinical practice. Although drug interactions resulting in death are rare, the effects of drug interactions are often misinterpreted as drug inefficacy or toxicity. Therefore an understanding of pharmacodynamic and pharmacokinetic drug interactions is essential when using polypharmacy. This chapter reviews the mechanisms of drug interactions, describes the most commonly seen drug interactions and offers suggestions for addressing drug interactions in clinical practice. Given polypharmacy is common in psychiatry; clinicians must routinely assess which medication combinations are safe to prescribe, require dose adjustments and are best avoided. Future research should focus on the role of genetics and interventions to decrease adverse drug reactions related to drug interactions.

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Abbreviations

CNS:

Central nervous system

CYP450:

Cytochrome P450

EPS:

Extrapyramidal side effects

GABA:

Gamma-amino butyric acid

INR:

International normalized ratio

MAOI:

Monoamine oxidase inhibitor

NSAID:

Non-steroidal anti-inflammatory drug

PD:

Pharmacodynamic

P-gp:

P-glycoprotein

PI:

Prescribing information

PK:

Pharmacokinetic

PPI:

Proton pump inhibitor

QTc:

Corrected QT interval

SNRI:

Serotonin, norepinephrine reuptake inhibitor

SSRI:

Selective serotonin reuptake inhibitor

TCA:

Tricyclic antidepressant

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Author information

Authors and Affiliations

  1. Department of Pharmacy Practice, University of Rhode Island, Kingston, RI, USA

    Jessica L. Gören PharmD, BCPP & Ashley Tewksbury PharmD

  2. Department of Psychiatry, Harvard Medical School, Boston, MA, USA

    Jessica L. Gören PharmD, BCPP

  3. Community Health Network, Indianapolis, IN, USA

    Ashley Tewksbury PharmD

Authors
  1. Jessica L. Gören PharmD, BCPP
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  2. Ashley Tewksbury PharmD
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Corresponding author

Correspondence to Jessica L. Gören PharmD, BCPP .

Editor information

Editors and Affiliations

  1. Sha'ar Menashe Mental Health Center, Hadera, 38814, Israel

    Michael S. Ritsner

Appendix. Commonly Encountered PsychotropicInteractions [9, 47, 59, 74]

Appendix. Commonly Encountered PsychotropicInteractions [9, 47, 59, 74]

Drug

Comment

Second generation antipsychotics

Aripiprazole

Adjust dose with 2D6/3A4 inducers and inhibitors

Long half life, maximum effects not seen for 3 weeks

Asenapine

Additive QTc prolongation potential

Adjust dose with 1A2 inducers and inhibitors

Clozapine

Decreased levels in cigarette smokers

Adjust dose with 1A2 inducers and inhibitors

Iloperidone

Adjust dose with 2D6 inducers and inhibitors

Lurasidone

Adjust dose with 3A4 inducers and inhibitors

Olanzapine

Decreased levels in cigarette smokers

Adjust dose with 1A2 inducers and inhibitors

Additive cardiopulmonary depression (IM highest risk)

Paliperidone

Adjust dose in renal impairment

Risperidone

Adjust dose in renal impairment

Additive QTc prolongation potential

Adjust dose with 2D6 inducers and inhibitors

Quetiapine

Adjust dose with 3A4 inducers and inhibitors

Additive QTc prolongation potential

Ziprasidone

Must be taken with food for absorption

Additive QTc prolongation potential

Increased risk of QTc prolongation with inhibitors

First generation antipsychotics

Chlorpromazine

Adjust dose with 2D6 inducers and inhibitors

Fluphenazine

Adjust dose with 2D6 inducers and inhibitors

Haloperidol

Adjust dose with 2D6 and 3A4 inducers and inhibitors

Additive QTc prolongation potential (IV highest risk)

Perphenazine

Adjust dose with 2D6 inducers and inhibitors

Thioridazine

Additive QTc prolongation potential

 

Increases levels of 2D6 substrates

Trifluoperazine

Adjust dose with 1A2 inducers and inhibitors

Anticonvulsants

Carbamazepine

Decreases levels of 1A2, 2B6, 2C19, 2C9, 2D6, 3A4 substrates

 

Decreased oral birth control efficacy

 

Lamotrigine

 

Levels significantly increased with valproate

Oxcarbazepine

Decreases levels of 3A4 substrates

Valproate

Significantly increases lamotrigine levels

Increases TCA levels

Antidepressants

Bupropion

Inhibits metabolism of 2D6 substrates

Citalopram

Adjust dose with 2C19 and 3A4 inhibitors

Additive QTc prolongation potential

Duloxetine

Adjust dose with 2D6 inducers and inhibitors

Mirtazapine

Adjust dose with 1A2, 2D6, 3A4 inducers and inhibitors

May decrease alpha antagonist effect

Nefazodone

Adjust dose with 3A4 and 2D6 inducers and inhibitors

Increases concentration of 3A4 substrate

MAOIs

Hypertensive crisis

Serotonin syndrome

SSRIs/SNRIs

Substrates, inducers and inhibitors of CYP450 enzymes (see Table 3.6)

Increased bleeding with anticoagulants and NSAIDs

TCAs

Substrates, inducers and inhibitors of CYP450 enzymes (see Table 3.6)

Benzodiazepines

Alprazolam

Adjust dose with 3A4 inducers and inhibitors

Chlordiazepoxide

Adjust dose with 3A4 inducers and inhibitors

Clonazepam

Adjust dose with 3A4 inducers and inhibitors

Diazepam

Adjust dose with 2C19, 3A4 inducers and inhibitors

Traizolam

Adjust dose with 3A4 inducers and inhibitors

Opiates

Buprenorphine

Adjust dose with 3A4 inducers and inhibitors

Methadone

Significant QTc prolongation

 

Adjust dose with 2B6 and 3A4 inducers/inhibitors

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Gören, J.L., Tewksbury, A. (2013). Drug Interactions and Polypharmacy. In: Ritsner, M. (eds) Polypharmacy in Psychiatry Practice, Volume I. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5805-6_3

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