title: Pharmacogenetics for off-patent antipsychotics: reframing the risk for tardive dyskinesia and access to essential medicines.
abstract: First-generation antipsychotics (FGAs) induce tardive dyskinesia, a debilitating involuntary hyperkinetic movement disorder, in 20-50% of individuals with a psychotic illness during chronic treatment. There is presently no curative treatment or definitive predictive test for tardive dyskinesia. The authors note that the three antipsychotic drugs enlisted in the most recent (14th) World Health Organization Model List of Essential Medicines--chlorpromazine, fluphenazine and haloperidol--belong to the FGA therapeutic class. In this regard, the need to choose between the competing objectives of ensuring global access to affordable and efficacious medicines, such as FGAs, and the formidable long-term risk for tardive dyskinesia, may create an ethical conundrum. Pharmacogenetics has thus far been conceptually framed as a tool to individualize therapy with new drugs under patent protection. However, the authors suggest that pharmacogenetics may also improve access to pharmacotherapy through the reintroduction of affordable second-line generic drugs or FGAs with suboptimal safety, as first-line therapy, in targeted subpopulations in whom they present a lower risk for tardive dyskinesia. To impact positively on global public health and distributive justice, a directory complementary to the essential medicines library--one that enlists the 'essential biomarkers' required for optimal pharmacotherapy--may benefit patients who do not have adequate access to new antipsychotic medications. This review discusses pharmacogenetic associations of tardive dyskinesia that are in part supported by meta-analyses and the oxidative stress-neuronal degeneration hypothesis.
authors.affiliation: VA Long Beach Healthcare System, Southern California Institute for Research and Education, Department of Psychiatry and Human Behavior, College of Medicine, University of California, Irvine, Long Beach, CA 90822, USA. pgxethics@hotmail.com
authors.forename: Vural
authors.initials: V
authors.lastname: Ozdemir
authors.forename: Eleni
authors.initials: E
authors.lastname: Aklillu
authors.forename: Steven
authors.initials: S
authors.lastname: Mee
authors.forename: Leif
authors.initials: L
authors.lastname: Bertilsson
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Albers
authors.forename: Janice E
authors.initials: JE
authors.lastname: Graham
authors.forename: Michael
authors.initials: M
authors.lastname: Caligiuri
authors.forename: James B
authors.initials: JB
authors.lastname: Lohr
authors.forename: Christopher
authors.initials: C
authors.lastname: Reist
mesh_terms: D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000145:classification; D004409:Dyskinesia, Drug-Induced / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D010330:Patents as Topic; D010597:Pharmacogenetics / Q000379:methods*; D012307:Risk Factors; D012559:Schizophrenia / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics
chemical_list: D014150:Antipsychotic Agents