Abstract
Background: Tardive dyskinesia (TD) is an iatrogenic involuntary movement disorder occurring after extended antipsychotic use with unclear pathogenesis. CYP2D6 is a liver enzyme involved in antipsychotic metabolism and a well-studied gene candidate for TD. Materials methods: We tested predicted CYP2D6 metabolizer phenotype with TD occurrence and severity in our two samples of European chronic schizophrenia patients (total n = 198, of which 82 had TD). Results: TD occurrence were associated with extreme metabolizer phenotype, controlling for age and sex (p = 0.012). In other words, individuals with either increased and no CYP2D6 activity were at higher risk of having TD. Conclusion: Unlike most previous findings, TD occurrence may be associated with both extremes of CYP2D6 metabolic activity rather than solely for poor metabolizers.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1065-1072 |
| Number of pages | 8 |
| Journal | Pharmacogenomics |
| Volume | 21 |
| Issue number | 15 |
| DOIs | |
| State | Published - Oct 2020 |
Funding
The authors thank the Ministry of Research and Innovation of Ontario, for funding the IMPACT project. CC Zai, AK Tiwari, DJ DJ M\u00FCller and JL Kennedy have been supported by the Genome Canada Genomic Applications Partnership Program (GAPP) and the CAMH Foundation. DJ M\u00FCller was supported by the Canadian Institutes of Health Research (CIHR operating grant MOP 142192), the National Institutes of Health (R01MH085801), the CAMH Foundation (J Murphy Professorship) and received a Brain & Behaviour Research (NARSAD) Independent Investigator Award, the M Smith New Investigator Salary Prize for Research in Schizophrenia (CIHR) and an Early Researcher Award by the Ministry of Research and Innovation of Ontario. G Remington was supported by the Canadian Institutes of Health Research (CIHR), as well as the Research Hospital Fund \u2013 Canadian Foundation for Innovation (RHF-CFI). CC Zai, AK Tiwari, DJ M\u00FCller and JL Kennedy are investigators in two pharmacogenetic studies where genetic test kits were provided as in-kind contribution by Assurex Health (Myriad Neuroscience) to evaluate the feasibility of pharmacogenetic testing in clinical practice and potential benefits of pharmacogenetic testing compared with treatment as usual. They have not received any payments or received any equity, stocks or options from this company or any other pharmacogenetic companies. CC Zai, AK Tiwari, DJ M\u00FCller and JL Kennedy are authors in two filed genetic patents assessing risk for antipsychotic-induced weight gain. JL Kennedy has received honoraria from Novartis, Roche and Eli Lilly corporations, and is an unpaid member of the scientific advisory board of AssureRx Corp. HY Meltzer has received grants or is or was a consultant to: Abbott Labs, ACADIA, Alkemes, Bristol Myers Squibb, DaiNippon Sumitomo, Eli Lilly, EnVivo, Janssen, Otsuka, Pfizer, Roche, Sunovion and BiolineRx. HY Meltzer is a shareholder of ACADIA and Glaxo Smith Kline. In the past three years JA Lieberman reports having received research funding or is a member of the advisory board of Allon, Alkermes, Bioline, GlaxoSmithKline Intracellular Therapies, Lilly, Merck, Novartis, Pfizer, Pierre Fabre, Psychogenics, F Hoffmann-La Roche LTD, Sepracor (Sunovion) and Targacept. JA Lieberman receives no direct financial compensation or salary support for participation in these research, consulting or advisory board activities. SG Potkin: consultancy/board of advisors/honoraria: American Psychiatric Association, Astra Zeneca, Bristol-Myers Squibb, Cortex, Dainippon-Sumitomo, Janssen Pharmaceutica, Novartis, Otsuka, Pfizer, Roche, Schering Plough, Vanda; research grants: Amgen, Bristol-Myers Squibb, Dainippon Sumitomo, Elan, En Vivo, Forest Laboratories, Janssen Pharmaceutica, Merck, Novartis, Otsuka, Pfizer, Solvay Pharmaceuticals, Roche, Sunovion, NIH, Harvard Massachusetts General Hospital, Brigham and Women\u2019s Hospital, Vanda, speakers\u2019 bureau: Lundbeck, Otsuka, ISCTM, Novartis, Pfizer, Sunovion. In the past 3 years, G Remington has received consultant fees from HLS Therapeutics and Mitsubishi Tanabe Pharma Corporation, as well as research support from HLS Therapeutics. He holds no commercial investments in any pharmaceutical company. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.
Keywords
- CYP2D6
- metabolizer phenotype
- pharmacogenetics
- schizophrenia
- tardive dyskinesia
ASJC Scopus subject areas
- Molecular Medicine
- Genetics
- Pharmacology