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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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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