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Clinically Significant Interactions with Mood Stabilisers

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Applied Clinical Pharmacokinetics and Pharmacodynamics of Psychopharmacological Agents

Abstract

Mood stabilisers are associated with a wide range of clinically significant drug-drug interactions. The glucuronidation of lamotrigine is inhibited by valproate and induced by oral contraceptives, carbamazepine and phenytoin. Lamotrigine induces the glucuronidation of quetiapine. Valproate is an inhibitor of CYP2C9 and glucuronosyltransferase enzymes and increases plasma levels of some benzodiazepines, tricyclic antidepressants and lamotrigine. Valproate’s metabolism is inhibited by aspirin and erythromycin and induced by carbapenem antibiotics. Carbamazepine is involved in innumerable interactions largely because of its potent ability to induce the activity of CYP3A4 and, to a lesser degree, CYP1A2 enzymes. Carbamazepine thus lowers plasma levels of many drugs including many analgesics, antipsychotics, benzodiazepines, antidepressants and antimicrobial agents. The metabolism of carbamazepine is inhibited by diltiazem, verapamil, danazol, isoniazid and ticlodipine. Lithium is largely renally excreted, a process that is inhibited by NSAIDs, thiazide and loop diuretics, ACE inhibitors and some calcium channel blockers. Lithium may give rise to neurotoxicity when combined with antipsychotics or antidepressants.

Search Details

We searched PubMed and Embase in January 2015 using the search terms “metabolism”, “pharmacokinetic” and “interaction” with the following drug names: “valproate”, “valproic”, “divalproex”, “lamotrigine”, “carbamazepine” and “lithium”. We also referred official European Medicines Association Summaries of Product Characteristics for all drugs listed (accessed online January 30, 2015). Reference sections for all retrieved papers were scrutinised for further relevant papers.

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Authors and Affiliations

  1. Pharmacy Department, Maudsley Hospital, Denmark Hill, London, UK

    David Taylor PhD, FFRPS, FRPharmS

  2. Pharmacy Department, South London and Maudsley NHS Foundation Trust, Maudsley Hospital, Denmark Hill, London, UK

    Kalliopi Vallianatou MPharm, MRPharmS

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  1. David Taylor PhD, FFRPS, FRPharmS
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  2. Kalliopi Vallianatou MPharm, MRPharmS
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Correspondence to David Taylor PhD, FFRPS, FRPharmS .

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  1. Univ. North Texas Sys, Col Pharmacy, Department of Pharmacotherapy, FORT WORTH, Texas, USA

    Michael W. Jann

  2. Department of Pharmacotherapy, Univ. North Texas Sys, Col Pharm, FORT WORTH, Texas, USA

    Scott R. Penzak

  3. Department of Pharmacotherapy, Univ. North Texas Sys, Col Pharm., FORT WORTH, Texas, USA

    Lawrence J. Cohen

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Taylor, D., Vallianatou, K. (2016). Clinically Significant Interactions with Mood Stabilisers. In: Jann, M., Penzak, S., Cohen, L. (eds) Applied Clinical Pharmacokinetics and Pharmacodynamics of Psychopharmacological Agents. Adis, Cham. https://doi.org/10.1007/978-3-319-27883-4_17

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