Challenges and prospects in bridging precision medicine and artificial intelligence in genomic psychiatric treatment

Table 1 Evidence based pharmacogenetic associations for psychiatric medications

Drug category	Drug name	Gene	Genotype group	Pharmgkb top FDA label testing level	Available clinical guidelines	Major clinically relevant drug-gene interactions
Anti-dementia drugs	Donepezil	CYP2D6	UM or PM	Actionable PGx	No data	May result in altered systemic concentrations
Anti-dementia drugs	Galantamine	CYP2D6	PM	Informative PGx	No data	Results in higher drug exposure compared to NMs
Antidepressants	Amitriptyline	CYP2C19	UM, IM or PM	No data	CPIC, DPWG	May result in altered conversion of tertiary amines to secondary amines
Antidepressants	Amitriptyline	CYP2D6	UM, IM or PM	Actionable PGx	CPIC, DPWG	May result in altered systemic concentrations
Antidepressants	Bupropion	CYP2D6		Testing required		Potential drug-drug interaction
Antidepressants	Citalopram	CYP2C19	PM	Actionable PGx	CPIC, DPWG	Results in higher drug exposure and higher risk of adverse reaction (QT prolongation) compared to NMs
Antidepressants	Clomipramine	CYP2C19	UM	Actionable PGx	CPIC, DPWG	Results in decreased drug exposure and increased risk of ineffectiveness compared to NMs
Antidepressants	Clomipramine	CYP2D6	PM	Actionable PGx	CPIC, DPWG	May result in altered systemic concentrations
Antidepressants	Desvenlafaxine	CYP2D6	PM	Informative PGx	CPIC	No difference in plasma concentration from NMs
Antidepressants	Doxepin	CYP2C19	IM or PM	Actionable PGx	CPIC, DPWG	Results in higher drug exposure compared to NMs
Antidepressants	Doxepin	CYP2D6	UM, IM or PM	Actionable PGx	CPIC, DPWG	May result in altered systemic concentrations
Antidepressants	Duloxetine	CYP2D6	PM	Actionable PGx	CPIC, DPWG	Potential drug-drug Interaction. May result in higher drug exposure
Antidepressants	Escitalopram	CYP2C19	UM, IM or PM	Actionable PGx	CPIC, DPWG	May result in altered systemic concentrations
Antidepressants	Fluvoxamine	CYP2D6	PM	Actionable PGx	CPIC, DPWG	Results in higher drug exposure compared to NMs
Antidepressants	Imipramine	CYP2C19	PM	No data	DPWG	Results in higher drug exposure and higher risk of adverse reaction compared to NMs. Avoid use in PMs
Antidepressants	Imipramine	CYP2D6	UM, IM or PM	Actionable PGx	CPIC, DPWG	May result in altered systemic concentrations
Antidepressants	Nortriptyline	CYP2D6	UM, IM or PM	Actionable PGx	CPIC, DPWG	May result in altered systemic concentrations
Antidepressants	Paroxetine	CYP2D6	UM, IM or PM	Criteria Not Met	CPIC, DPWG	May result in altered systemic concentrations
Antidepressants	Sertraline	CYP2C19	PM	No data	CPIC, DPWG	Results in higher drug exposure and higher risk of adverse reaction compared to NMs
Antidepressants	Venlafaxine	CYP2D6	PM	Actionable PGx	CPIC, DPWG	Results in altered parent drug and metabolite concentrations
Antidepressants	Vortioxetine	CYP2D6	PM	Actionable PGx	CPIC	Results in higher drug exposure compared to NMs
Antidepressants	Amoxapine	CYP2D6	UM, IM or PM	Actionable PGx	No data	May result in altered systemic concentrations
Antidepressants	Desipramine	CYP2D6	UM, IM or PM	Actionable PGx	CPIC	May result in altered systemic concentrations
Antidepressants	Trimipramine	CYP2D6	UM, IM or PM	Actionable PGx	CPIC	May result in altered systemic concentrations
Antiepileptics	Carbamazepine	HLA-A	*31: 01 positive	Actionable PGx	CPIC, DPWG, CPNDS	Results in higher risk of adverse reaction risk (severe skin reactions) compared to NMs
Antiepileptics	Carbamazepine	HLA-B	*15: 02 positive	Testing required	CPIC, DPWG, CPNDS	Results in higher risk of adverse reaction risk (severe skin reactions) compared to NMs. Consider alternative therapies, or use only if potential benefits outweigh risks
Antiepileptics	Lamotrigine	HLA-B	*15: 02 positive	No data	DPWG	Results in higher risk of adverse reaction risk (lamotrigine-induced SJS/TEN). Avoid use in patients with *15: 02 positive allele
Antiepileptics	Oxcarbazepine	HLA-B	*15: 02 positive	Testing required	CPIC, DPWG	Results in increased risk of adverse reaction (severe skin reactions)
Antiepileptics	Phenytoin	CYP2C9	IM or PM	Testing recommended	CPIC, DPWG	May result in higher drug exposure and higher risk of adverse reaction (CNS toxicity) compared to NMs
Antiepileptics	Phenytoin	HLA-B	*15: 02 positive	Testing recommended	CPIC, DPWG	May result in higher risk of adverse reaction (SJS/TEN) compared to NMs
Antiepileptics	Valproic acid	POLG	A467T and W748S mutations	Testing required	No data	Results in increased risk of adverse reaction (acute liver failure and resultant deaths). The use is contraindicated in patients with POLG mutations
Antimigraine preparations	Clonidine	CYP2D6	UM, IM or PM	No data	DPWG	No significant effect (No recommendation). Possible alternative for atomoxetine in variant CYP2D6 metabolisers
Antipsychotics	Aripiprazole	CYP2D6	PM	Actionable PGx	DPWG	Results in higher drug exposure compared to NMs and higher risk of adverse reaction
Antipsychotics	Clozapine	CYP2D6	PM	Actionable PGx	DPWG	Results in higher drug exposure compared to NMs
Antipsychotics	Haloperidol	CYP2D6	UM or PM	Actionable PGx	DPWG	Results in increased risk of adverse reaction In PMs and higher risk of reduced effectiveness In UMs
Antipsychotics	Olanzapine	CYP2D6	PM	Informative PGx	DPWG	No significant effect (No recommendation)
Antipsychotics	Paliperidone	CYP2D6	PM	Informative PGx	No data	No significant difference in exposure or clearance compared to NMs
Antipsychotics	Perphenazine	CYP2D6	PM	Actionable PGx	No data	Results in higher drug exposure and higher risk of adverse reaction compared to NMs
Antipsychotics	Pimozide	CYP2D6	PM	Testing required	DPWG	Results in higher drug exposure compared to NMs
Antipsychotics	Quetiapine	CYP3A4	PM	No data	DPWG	Results in decreased conversion of systemic parent drug (quetiapine) to the active metabolite. Use alternative therapy
Antipsychotics	Risperidone	CYP2D6	UM, IM or PM	Informative PGx	DPWG	Results in altered parent drug and metabolite concentrations
Anxiolytics	Clobazam	CYP2C19	IM or PM	Actionable PGx	No data	Results in increased active metabolite concentrations and increased risk of adverse reaction as compared to NMs
Anxiolytics	Diazepam	CYP2C19	PM	Actionable PGx	No data	May result in altered systemic concentrations
Psycholeptics and psychoanaleptics in combination	Fluoxetine	CYP2D6	PM	Actionable PGx	CPIC, DPWG	Results in higher drug exposure compared to NMs
Psycholeptics and psychoanaleptics in combination	Fluoxetine	FKBP5	PM	Actionable PGx	CPIC, DPWG	Results in higher drug exposure compared to NMs
Psychostimulants, agents used for adhd and nootropics	Atomoxetine	CYP2D6	PM	Actionable PGx	CPIC, DPWG	Results in higher drug exposure and higher risk of adverse reaction compared to NMs
Psychostimulants, agents used for adhd and nootropics	Modafinil	CYP2D6	PM	Actionable PGx	No data	May require dose modification when administered with medication metabolized by CYP2C19

NM: Normal metabolizer; UM: Ultra-rapid metabolizer; IM: Intermediate metabolizer; PM: Poor metabolizer; CPIC: Clinical pharmacogenetics implementation consortium; DPWG: Dutch pharmacogenetics working group; CPNDS: Canadian pharmacogenomics network for drug safety; SJS/TEN: Stevens-Johnson syndrome; TEN: Toxic epidermal necrolysis; PGx: Pharmacogenomic.