Library Dissertation Showcase

The Concomitant Use of the Mood Stabilizers Lithium/Valproate Plus an Atypical Antipsychotic in the Treatment for Bipolar Disorder: A Systematic Review of the Efficacy and Occurrence of Adverse Drug Reactions

  • Year of Publication:
  • 2021

Background: Bipolar disorder (BD), sometimes referred to as manic depression, is a cyclical mood disorder characterised by a wide spectrum of signs and symptoms but typically manifests itself with periods of depression and periods of abnormally elevated moods, sometimes occurring interchangeably, that can last from just days to weeks at a time (Anderson et al, 2012). The complex variability of symptoms associated with BD often results in a combination of different treatments being the preferred approach to control and manage these symptoms. Despite the concomitant use of atypical antipsychotics (AAPs) and mood stabilizers frequently proving to be more efficacious in comparison to monotherapy, there is still concern over the apparent increased occurrence of ADRs associated with such combination.
Aim: With the support of educational research and evaluation this project will be assessing the relationship between polypharmacy, specifically the use of mood stabilizers in combination with AAPs. As well as considering the potential benefit that can be derived from a combination treatment, despite the apparent increased occurrence of adverse drug reactions, a systematic review of previous literature will be carried out with the aim of evaluating whether the increased efficacy outweighs the potential increased risk of ADRs in bipolar polypharmacy.
Results: Several different studies have been found to corroborate the efficacy of AAPs (with particular note to risperidone, olanzapine and quetiapine and aripiprazole) in the long-term treatment of BD when used in combination with mood stabilizers, mainly lithium and valproate. However, the use of a combination treatment does appear to have the potential to increase the risk of adverse drug reactions which may have serious implications on long-term compliance. Monitoring of drug plasma concentration and presented symptoms may be necessary to avoid the occurrence of more severe ADRs.
Method: The pharmacodynamic and pharmacokinetic activities of AAPs and mood stabilizers will be explored in order to determine any potential sites of drug-drug interactions (DDIs) between certain mood stabilized and AAPs, in order to predict whether one drug may upregulate or downregulate the activity of another. DDIs can alter the plasma concentration of a drug which may result in therapeutic failure (if the concentration is below the minimum effective dose) or toxicity and subsequently ADRs (if the concentration is above the maximum tolerated dose).
Discussion: The extent of the effect genetic polymorphs in key metabolizing enzymes and receptor sites on the potential occurrence of ADRs will be discussed. The benefits and barriers to pharmacogenomic testing will also be addressed in an attempt to determine whether a ‘one size fit all’ approach could ever be replaced with a more personalized treatment method and, if so, how might this impact the future of prescribing and drug design/development.
Conclusion: Even though there is evidence to show the concomitant use of mood stabilizers and AAPs is more efficacious compared to monotherapy and usually well tolerated, there does appear to be some populations of patients who could be negatively affected by their concomitant use. Implementing pharmacogenomic (PGx) testing and therapeutic drug monitoring (TDM) could potentially reduce the incidence and severity of ADRs in populations who are predisposed to AAP toxicity. Further research is needed into the use of psychoeducation (PE) in addition to pharmacological treatment to determine its impact on patient treatment outcomes.

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