Pharmacogenetics for Severe Mood Disorders: A Randomised Controlled Trial

CNSDose (formerly known as Amplis – EVO™ Mental Health genetic test) is pharmacogenetic-based clinical decision support tool. Pharmacogenetic-based decision support tools provide information that are relevant for selecting drugs and/or dosage and can also provide information on drug-drug interactions (based on the patient’s current medication regime) in addition to reporting on genotype profile and predicted phenotype. The test includes assays for 16 genes (CYP2D6, CYP2C9, CYP2C19, CYP1A2, CYP3A4, CYP3A5, CYP2B6, UGT1A1, ABCB1, ABCC1, ABCG2, CES1, COMT, OPRM1, SLCO1B1 & VKORC1) involved in the metabolism and transport of antidepressant medication. Genetic material is provided from a buccal (cheek) cell sample which involves a simple swab of the inside of the cheeks with a sterile cotton swab. Treating clinicians will receive a report based on analysis of the genetic sample. The report will contain an antidepressant guidance section and a current regimen risk chart which includes genetic and non-genetic risk components. This tool can assist clinicians prescribing decisions in the treatment of severe mood disorders by reducing the risks of adverse medical reactions, support the selection of optimal first-time treatment and avoid polypharmacy issues in elderly patients. Once eligibility for the study is confirmed and informed consent obtained, participants will be randomised into one of two groups: Group 1 - CNSDose-guided prescribing In addition to standard care, participants assigned to this arm will have their pharmacotherapy guided by the CNSDose report based on their genetic test. The genetic test involves a simple buccal swab which takes about 5 minutes and will be sent to the lab on the same day for processing. The lab processing will take about 3 days. The results of the CNSDose test (contained in a report) will be sent to the treating clinicians within a week of the swab to enable tailoring of pharmacotherapy. However use of the CNSDose report is not mandatory for clinicians. At the end of the study (or early withdrawal of a participant), the patients' files will be audited to check if the CNSDose report was used to guide pharmacotherapy and if so, any effects it might have had. Participant adherence to medication will be monitored using the Morisky Medication Adherence Scale which will be administered at each of the 4 follow-up study visits after the baseline visit. Group 2 - Standard prescribing (unguided) Following randomisation, participants will provide a Buccal Swab for genetic testing and completed a health questionnaire, depression rating scale, mania rating scale (only for participants with a diagnosis of Bipolar Disorder) and have their vital signs recorded. These assessments will be repeated at 4 weekly intervals until week 12, then again at week 24 as well as complete a medication-taking adherence scale and a side effects rating scale. All assessments will be conducted by an experienced Trial Coordinator and Study Investigator. Participant visits will be aligned with their regular outpatient visits where possible. If this is not possible then the participant follow-up visits can be conducted remotely i.e. over the phone or via web-based platform if the participant can not make it to the site.