Table 4.
Overview of recommendations by various agencies and expert groups for actionable gene-antipsychotic pairs
| Drug labels with PGx information [148, 149] | PGx drug dosing guidelines (related biomarker) [152] | CPIC level [150] | PharmGKB level of evidence [149] | ||||
|---|---|---|---|---|---|---|---|
| FDA | EMA | HCSC | PMDA | ||||
| Aripiprazole | Actionable PGx | Actionable PGx | Actionable PGx | N/A | DPWG (CYP2D6) | B | CYP2D6 3 |
| Aripiprazole lauroxil | Actionable PGx | N/A | N/A | N/A | N/A | N/A | N/A |
| Brexpiprazole | Actionable PGx | N/A | N/A | N/A | N/A | B | CYP2D6 N/A |
| Clozapine | Actionable PGx | N/A | N/A | N/A | DPWG (CYP2D6) | C D |
CYP2D6 No literature support found for PGx HTR2C 2B |
| Haloperidol | N/A | N/A | N/A | N/A | DPWG (CYP2D6) |
C | CYP2D6 3 |
| Iloperidone | Actionable PGx | N/A | N/A | N/A | N/A | B/C | CYP2D6 3 |
| Olanzapine | N/A | Informative PGx | N/A | N/A | DPWG (CYP2D6) |
C D |
CYP2D6 3 HTR2C 2B |
| Perphenazine | Actionable PGx | N/A | N/A | Actionable PGx |
N/A | B/C | CYP2D6 N/A |
| Pimozide | Testing required | N/A | N/A | N/A | N/A | B | CYP2D6 4 |
| Risperidone | Informative PGx | N/A | Informative PGx | N/A | DPWG (CYP2D6) |
B C D |
CYP2D6 2A DRD2 2A HTR2C 2B |
| Thioridazine | Actionable PGx | N/A | N/A | N/A | N/A | C | CYP2D6 3 |
| Zuclopenthixol | N/A | N/A | N/A | N/A | DPWG (CYP2D6) |
C | CYP2D6 3 |
The definition of PGx level is outlined below: “testing required” = stating or implying that some sort of genetic testing should be conducted before using this drug; “actionable PGx” = not discussing genetic testing for gene variants, but containing information regarding changes in efficacy, dosage, or toxicity due to such variants; “informative PGx” = mentioning a gene involvement in the metabolism or pharmacodynamics of the drug, but there is no information to suggest that variation in these genes leads to a different response. The definition of CPIC level is outlined as below: A = genetic information should be used to change prescription of the affected drug; B = genetic information could be used to change prescription of the affected drug; C = no actions for prescription are recommended, because the alternatives are unclear or evidence is weak; D = there are few data. PharmGKB level of evidence: “level 1A” and “level 1B” refer to high evidence, “level 2A” and “level 2B” refer to moderate evidence, and “level 3” refers to low evidence regarding an association of a variant-drug combination. CPIC, Clinical Pharmacogenetics Implementation Consortium; DPWG, Royal Dutch Association for the Advancement of Pharmacy − Pharmacogenetics Working Group; EMA, European Medicines Agency; FDA, Food and Drug Administration; HCSC, Health Canada (Santé Canada); N/A, not applicable; PGx, pharmacogenetics/pharmacogenomics; PharmGKB, Pharmacogenomics Knowledgebase; PMDA, Pharmaceuticals and Medical Devices Agency, Japan.