Pharmacist Guided Pre-emptive Pharmacogenetic Testing in Antidepressant Therapy

Study Overview
=================
Brief Summary
-----------------
In this study at the Solothurn Psychiatric Clinic, the investigators compare the effectiveness and tolerability of antidepressant pharmacotherapy in three groups. In the intervention group, the physician selects and doses the medication for depression based on a pharmacogenetic examination conducted by a clinical pharmacist. In the standard group, the treating physician selects and doses the antidepressant drug without the support of genetic testing, in accordance with current standard practice. If after the first week of hopsitalization no adjustment to a new antidepressant is necessary, the investigators will monitor the progress of these patients until they leave the clinic in an observational arm. The drugs used are all approved in Switzerland for the treatment of depression. Classification into the intervention or standard group is made randomly after the first week of hospitalisation, if the treating physician deems it necessary to change or readjust the antidepressant pharmacotherapy. The probability of allocation to one of the two study groups is 50%. All study participants will be hospitalized for at least five weeks and monitored until they leave the clinic. In total, it is planned to include and examine 95 patients each into the intervention and standard group.

Official Title
-----------------
Pharmacist Guided Pre-emptive Pharmacogenetic Testing in Antidepressant Therapy

Conditions
-----------------
Depression

Intervention / Treatment
-----------------
* Procedure: Pharmacist-guided pharmacogenetic (PGx) testing for antidepressant selection and dosing
* Procedure: Standard care antidepressant selection and dosing


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: ≥ 18 years old Diagnosis unipolar moderate or severe depressive episode or recurrent depressive disorder (ICD10: F32.1/32.2/33.1/33.2) HAM-D17 ≥ 17 Exclusion Criteria: Acute suicide risk Psychotic symptomatology Other acute serious psychiatric disorder other than depression Excessive consumption of alcohol and/or drugs Severe acute - or severe chronic somatic diseases Pregnant / lactating women Under current treatment with fluoxetine

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br> | Procedure: Pharmacist-guided pharmacogenetic (PGx) testing for antidepressant selection and dosing<br>* The study intervention is the service of pharmacist guided pre-emptive PGx testing to support clinical decision making for antidepressant selection and dosing. This service involves genotyping and thereof evidence-based genotype interpretation commercially offered as Stratipharm® (humatrix AG, Pfungstadt Germany, https://www.stratipharm.de). Furthermore, clinical pharmacists will process and evaluate the results from PGx testing (Stratipharm®) in context of the individual patient medication history as well as current co-medication and forward an individualized recommendation for antidepressant selection and dosing to the treating psychiatrist.<br>|
| Active Comparator: Standard Care<br> | Procedure: Standard care antidepressant selection and dosing<br>* Selection and dosing of the new antidepressant pharmacotherapy will be determined by the treating investigator alone, according to current standard of care considering clinical factors only.<br>|
| No Intervention: Observational<br> | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rate of response to the antidepressant therapy at the end of week 4 | response is determined as a reduction in the Hamilton Depression (HAM-D17) Scale score of at least 50 % of the baseline value | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to response | time span from start of antidepressant pharmacotherapy until first assessed response (= HAM-D17 reduction of at least 50 % compared to baseline | 28 days | 
| Remission rate | 17 item Hamilton rating scale for Depression (HAM-D17) score ≤ 8 | 28 days | 
| Overall change in 17 item Hamilton rating scale for Depression (HAM-D17) from baseline to week 4 | minimum value: 0, maximum value: 52 ; higher scores mean worse outcome | 28 days | 
| Time till discharge | time span from admission (randomization) to discharge from inpatient treatment | assessed up to 3 month | 
| Patient depression self-rating | two weekly assessment with Beck's Depression Inventory questionnaire (BDI-II) | 28 days | 
| Side effect measure (self-rated frequency, intensity and burden of side effects, FIBSER score) | weekly assessment, minimum value: 0, maximum value: 18 ; higher scores mean worse outcome | 28 days | 
| Number of adverse events related to antidepressant pharmacotherapy | severity grading ≥ 2 (using CTCAE version 5.0) and causality to antidepressant pharmacotherapy assessed as possible, probable or definite | 28 days |