Proportion of Antipsychotics with CYP2D6 Pharmacogenetic (PGx) Associations Prescribed in an Early Intervention in Psychosis (EIP) Cohort: A Cross-Sectional Study

Abstract

Background: Prescribing drugs for psychosis (antipsychotics) is challenging due to high rates of poor treatment outcomes, which are in part explained by an individual's genetics. Pharmacogenomic (PGx) testing can help clinicians tailor the choice or dose of psychosis drugs to an individual's genetics, particularly psychosis drugs with known variable response due to CYP2D6 gene variants ('CYP2D6-PGx antipsychotics').

Aims: This study aims to investigate differences between demographic groups prescribed 'CYP2D6-PGx antipsychotics' and estimate the proportion of patients eligible for PGx testing based on current pharmacogenomics guidance.

Methods: A cross-sectional study took place extracting data from 243 patients' medical records to explore psychosis drug prescribing, including drug transitions. Demographic data such as age, sex, ethnicity, and clinical sub-team were collected and summarised. Descriptive statistics explored the proportion of 'CYP2D6-PGx antipsychotic' prescribing and the nature of transitions. We used logistic regression analysis to investigate associations between demographic variables and prescription of 'CYP2D6-PGx antipsychotic' versus 'non-CYP2D6-PGx antipsychotic'.

Results: Two-thirds (164) of patients had been prescribed a 'CYP2D6-PGx antipsychotic' (aripiprazole, risperidone, haloperidol or zuclopenthixol). Over a fifth (23%) of patients would have met the suggested criteria for PGx testing, following two psychosis drug trials. There were no statistically significant differences between age, sex, or ethnicity in the likelihood of being prescribed a 'CYP2D6-PGx antipsychotic'.

Conclusions: This study demonstrated high rates of prescribing 'CYP2D6-PGx-antipsychotics' in an EIP cohort, providing a rationale for further exploration of how PGx testing can be implemented in EIP services to personalise the prescribing of drugs for psychosis.

Keywords: Antipsychotics; Personalised Medicine; Pharmacogenetics; Pharmacogenomics; Psychosis; Receptor Antagonist (D2); Receptor Antagonist (D2, 5-HT2); Receptor Antagonist (D2, 5-HT2, NE, alpha-2); Receptor Partial Agonist (D2, 5-HT1A); Schizophrenia.

Figure 1.

Study inclusion and exclusion flowchart. Flowchart showing patients assessed for eligibility.

Figure 2.

Psychosis drugs classification process. To be classified as a ‘CYP2D6-PGx antipsychotic’ for the study, a psychosis drug required a CYP2D6 PGx association that has a supporting level of evidence (LoE) of the highest possible assigned level 1A (as graded by PharmGKB).

Figure 3.

Currently prescribed drugs for psychosis: (a) ‘CYP2D6-PGx antipsychotics’ and (b) ‘non-CYP2D6-PGx antipsychotics’. Currently prescribed psychosis drugs based on PGx grouping. (a) ARI: Aripiprazole; RIS: Risperidone; HAL: Haloperidol; ZUC: Zuclopenthixol. (b) OLA: Olanzapine; QUE: Quetiapine; PAL: Paliperidone; AMI: Amisulpride; FLU: Flupentixol; CLO: Clozapine.

Figure 4.

Proportion of retrospective psychosis drug transitions grouped by type of transition. Displayed is the proportion of ‘antipsychotic-to-antipsychotic’ transitions, grouped by the different types of psychosis drug transition. Transition types: ‘2D6 to 2D6’ = ‘CYP2D6-PGx antipsychotic’ to another ‘CYP2D6-PGx antipsychotic’; ‘2D6 to non-2D6’ = ‘CYP2D6-PGx antipsychotic’ to a ‘non-CYP2D6-PGx antipsychotic’; ‘non-2D6 to 2D6’ = ‘non-CYP2D6-PGx antipsychotic’ to a ‘CYP2D6-PGx antipsychotic’; ‘non-2D6 to non-2D6’ = ‘non-CYP2D6-PGx antipsychotic’ to ‘non-CYP2D6-PGx antipsychotic’.

Figure 5.

Eligibility for PGx testing. Flow diagram showing the likelihood of included patients being prescribed a ‘CYP2D6-PGx antipsychotic’ at any time (either currently or previously prescribed) and of the proportion that experienced two or more psychosis drug transitions. More specifically, the flow diagram shows that of those who experienced two or more transitions, 49 (20%) patients were prescribed two or more ‘CYP2D6-PGx antipsychotics’ and 56 (23%) patients met the suggested eligibility for having a PGx test, based on current guidelines (Van Westrhenen et al., 2021b).

Figure 6.

Common psychosis drug transitions. Mapped are the 10 most prevalent psychosis drug transitions that occurred for included patients. Highlighted in light blue are ‘CYP2D6-PGx antipsychotics’. Only one transition (olanzapine to quetiapine) did not involve a ‘CYP2D6-PGx antipsychotic’. The number assigned to each arrow is the total count for that specific transition (out of a total of 246 transitions).

Figure 7.

Documented reason(s) for psychosis drug transitions. ADRs/Tolerability was the most common reason, followed by a lack of therapeutic response (lack of TR), and then patient refusal to take and mixed/more than one documented reason. Other reasons included a prolonged period in symptom remission, a switch to an intramuscular depot formulation and when the reason was not stated.

Figure 8.

Common psychosis drug transitions stratified by documented reason (s) for the transition. Displayed are the documented reasons for ‘antipsychotic-to-antipsychotic’ transitions for each of the top ten most common individual-specific transition types. ADRs/Tolerability issues were the most common reasons for these transitions, followed by a Lack of Therapeutic Response (Lack of TR) and then ‘Other’ reasons. Although the proportion of reasons varied by the specific antipsychotic-to-antipsychotic transition. For the ‘Risperidone to Paliperidone’ switch, all the ‘Other’ reasons were due to a switch from oral Risperidone to a Paliperidone intramuscular depot injection. Less common reasons included Patient Refusal to Take and ‘Mixed’ reasons. ARI: aripiprazole; RIS: risperidone; HAL: haloperidol; ZUC: zuclopenthixol; OLA: olanzapine; QUE: quetiapine; PAL: paliperidone.