Lithium pharmacogenetics: Low levels of evidence

24 Aug Lithium pharmacogenetics: Low levels of evidence

Genetic differences can cause a medication to work effectively in one person while failing to help, or even causing harm in another person. Pharmacogenetic testing detects these differences and can prevent adverse drug reactions (ADRs) and ineffective treatments. Pharmacogenomics is an evolving field of research and informs prescription decisions for a growing number of medications. However, pharmacogenetic testing is not available for all medications. Currently, there is no clear evidence for the clinical use of pharmacogenetics with lithium and the levels of evidence in PharmGKB are 3 and 4. PharmGKB is a NIH-funded database that curates knowledge about the impact of genetic variation on drug response and is an important resource for finding dosing guidelines and studies on how certain medications are affected by a person’s genetic information.

Lithium is primarily used as a psychiatric medication and is an important part of bipolar disorder treatment. There is evidence that lithium reduces the risk of all-cause and suicide mortality in patients with bipolar who have attempted suicide in the past. Considering the inter-individual variability when prescribing, may result in safer and more effective opioid formulations.

There is one study referenced by PharmGKB that indicated a potential link between a variant in a gene called ABCB1 and risk of suicidal ideation while taking lithium ¹. Patients in this study were on various combinations of six different medications, and although patients with the ABCB1 gene variant had an increased risk of suicidal ideation, this was not associated with any particular medication. Most importantly, adding lithium to their other medications did not increase the risk of suicidal ideation at all, regardless of genetics.

Therefore, reporting that a patient with the ABCB1 variant is at increased risk of suicidal ideation when using lithium would be inaccurate based on current evidence. It may be dangerous if a patient decides not to use lithium based on this information, since untreated bipolar can have many potential consequences on physical and mental health.

1. Perroud N, Bondolfi G, Uher R, Gex-Fabry M, Aubry JM, Bertschy G, Malafosse A, Kosel M. (2011) Clinical and genetic correlates of suicidal ideation during antidepressant treatment in a depressed outpatient sample.Pharmacogenomics

TreatGxplus is an evidence-based pharmacogenetic service that provides safe, effective, and personalized prescribing options. Lithium is included in TreatGxplus as a treatment option for biopolar I disorder and is dose-adjusted based on bipolar stage and renal function. Since there is no clinical evidence showing a clear association of genetic variants with an increased risk of side effects or altered efficacy, TreatGxplus does not include a pharmacogenetic test for lithium.