Feng, Xiaodong_ Xie, Hong-Guang - Applying pharmacogenomics in therapeutics-CRC Press (2016)

Pharmacogenomics of CNS Disorder Treatments
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necessary to overcome the statistical penalty acquired by the genotyping of hundreds
of thousands of single nucleotide polymorphisms (SNPs). 8 To date, GWASs
have not yet been useful in predicting genome-wide significant or clinically useful
predictors of antidepressant response, lithium treatment response, or antipsychotic
drug response. 9–16 Other limitations to the use of GWASs include the use of chronic
patients, lack of medication adherence monitoring, and ambiguity of phenotype
definition. 2
Key Points: The translation of pharmacogenomic testing into clinical practice
has several limitations in CNS disorders as below:
1. Lack of clear relationships between the serum concentrations of many
neuropsychiatric drugs and response to treatment
2. Wide therapeutic ranges for many neuropsychiatric drugs
3. Lack of clinical guidelines and limited number of well-designed trials
investigating the use of genomic testing in methods that could be translated
into clinical practice
4. Use of multiple drugs to treat neuropsychiatric illnesses, which complicates
the understanding of how and when to utilize available testing
options
5. Diverse ethnicities of the patients with CNS disorders
The Clinical Pharmacogenomics Implementation Consortium established in
2009, was formed to establish evidence-based pharmacogenetic guidelines and
disseminate them to clinicians in the field. The guidelines created are designed
to assist and guide drug therapy in situations when genetic information is available,
but the guidelines do not specifically state if or for whom pharmacogenetic
testing should be obtained (www.pharmgkb.org). 17 Currently, the group has
established or is in the process of establishing guidelines for the use of tricyclic
antidepressants, selective serotonin reuptake inhibitors (SSRIs), carbamazepine,
phenytoin, and valproic acid. The website offers a convenient interface to enter
the patient’s genotype for specific dosing recommendations given to the drugs
they are prescribed.
Patient Case
RJ, a 55-year-old female widowed school teacher, has been admitted to the inpatient
psychiatric unit after a suicide attempt. RJ has a history of mild cognitive impairment
and has been experiencing symptoms of depression after the passing of her husband
six months ago. RJ describes her days as being spent sleeping and not eating.
She is unable to concentrate on things, rereading the same newspaper article several
times. She feels guilty about her husband’s passing, stating how she should have died
first. At admission, RJ is receiving donepezil 10 mg daily, lisinopril 10 mg daily,
metformin 500 mg twice daily, omeprazole 20 mg daily, and a multivitamin daily.