Pharmacogenetics for Severe Mood Disorders: A Randomised Controlled Trial

INTERVENTION: Amplis – EVO™ Mental Health genetic test (Amplis) 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 ‐ Amplis‐guided prescribing In addition to standard care, participants assigned to this arm will have their pharmacotherapy guided by the Amplis 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 CONDITION: Mental Health ‐ Depression Public Health ‐ Health service research Severe Mood Disorders;Major Depressive Disorder;Bipolar Disorder; ; Severe Mood Disorders ; Major Depressive Disorder ; Bipolar Disorder PRIMARY OUTCOME: A 10% difference in remission rate for patients with Bipolar Disorder (BD) indicated by a Young Mania Rating Scale (YMRS) score of less than or equal to 12.[This outcome will be measured at enrolment (week 0), and weeks 4, 8, 12 and 24 (primary timepoint) post‐enrolment.] A 10% difference in remission rate for patients with Major Depressive Disorder (MDD) indicated by a Montgomery‐Asberg Depression Rating Scale (MADRS) score of less than 10.[This outcome will be measured at enrolment (week 0), and weeks 4, 8, 12 and 24 (primary timepoint) post‐enrolment. ] INCLUSION CRITERIA: 1. Have a primary diagnosis of MDD or BD. 2. Are currently experiencing a manic, mixed or depressive episode (for those with BD diagnosis) 3. Are admitted or referred to the participating site 4. Have been prescribed or willing to be prescribed an antidepressant and/or mood stabiliser 5. Are aged 18 years or older 6. Sufficiently proficient in English to enable completion of the self‐reported study assessment tools. SECONDARY OUTCOME: A change in the response rate defined as a greater than 50% change on the MADRS in the Amplis group compared with the unguided group.[This outcome will be measured at enrolment (week 0), and weeks 4, 8, 12 and 24 post‐enrolment.] A change in the treatment dropout rate as all‐cause discontinuation during the treatment period in the Amplis group compared with the unguided group.[This outcome will be assessed at weeks 4, 6, 8, 12 and 24 post enrolment by a combination of an audit of patients' medical files and telephone follow‐up calls.] Adverse event monitoring will be performed as part of the medication safety parameters. This will be done through a combination of patient interview at study visits and audit of patient files.[This will be assessed at enrolment (week 0), and weeks 4, 8, 12, and 24 post‐enrolment.] Change in treatment outcomes, specifically change in depression severity during the study period. This will be assessed by completion of the nine item Patient Health Questionnaire (PHQ‐9).[This outcome will be measured at enrolment (week 0) and weeks 4, 6, 8, 12 and 24 post‐enrolment.] Medication review will be undertaken during the study period to determine if there have been any changes to medication and dosages. This will be done through a combination of patient interview during the study visits and audit of patient files.[This will be conducted at enrolment (week 0) and weeks 4, 8, 12, and 24 postt‐enrolment.] The effects of participants' genetic profile on their reaction to medication will be assessed by having a buccal swab.[This test will only be done at enrolment (week 0).] The rate of medication side effects will be monitored by completion of the Frequency, Intensity, Burden of Side Effects Rating (FIBSER) scale. [This outcome will be assessed at weeks 4, 8, 12, and 24.] Vital signs will be assessed for the study period as part of safety parameter monitoring of medication. This will include: blood pressure and heart rate (using a blood pressure machine), oxygen saturation (using a pulse oximeter), temperature (using tympanic thermometer), respiratory rate (manual count of breaths/min) and body/mass index calculated from weight (using a calibrated digital scale) and height (using a stadiometer).[These outcomes will be measured at enrolment (week 0) and weeks 4, 8, 12, and 24 post‐enrolment.]