Testing a Pharmacogenetic-Guided Treatment Selection Strategy with Antidepressant Drug Combination for Patients with Depressive Disorder

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What is this study about?

This study involves people with depressive disorder who are starting a new treatment after their previous medication did not work well enough. The study will test several different antidepressant medications taken by mouth, including vortioxetine, escitalopram, sertraline, quetiapine, bupropion, clomipramine, venlafaxine, imipramine, fluoxetine, mianserin, duloxetine, agomelatine, amitriptyline, nortriptyline, fluvoxamine, mirtazapine, paroxetine, citalopram, trimipramine, and desvenlafaxine. These medications are all types of antidepressants, which are drugs used to treat depression by affecting chemicals in the brain that influence mood.

The purpose of this study is to find out whether using genetic testing before choosing an antidepressant medication leads to better results compared to the usual way doctors select these medications. The genetic testing looks at specific genes that can affect how a person’s body processes antidepressant medications and how well they might respond to treatment. The study will compare two groups of patients: one group will have their treatment chosen based on genetic test results along with other medical information, while the other group will receive treatment selected in the standard way without genetic testing. The study aims to see which approach helps patients feel better faster and with fewer side effects.

Participants will be followed for 16 weeks after starting their new antidepressant medication. During this time, they will have regular visits with their doctor to check how well the treatment is working and whether they are experiencing any side effects. The study will measure improvement in depression symptoms using questionnaires that ask about mood, energy, sleep, and other aspects of daily life. Doctors will also track how many times the medication needs to be changed or adjusted, how many doctor visits are needed, and whether any unwanted effects occur. The study will also look at the costs of both treatment approaches to see if genetic testing provides good value.

1 Initial assessment and baseline evaluation

At the beginning of the trial, your depression symptoms will be evaluated using two questionnaires. The first is called PHQ-9 (Patient Health Questionnaire-9), which measures depression severity. The second is MADRS (Montgomery-Asberg Depression Rating Scale), another tool to assess depression symptoms. Both assessments will be completed within two weeks before your entry into the study.

Your medical history will be reviewed to confirm that you are currently experiencing your first depressive episode and that you are receiving medication for depression. The review will also verify that you have tried no more than one previous antidepressant treatment.

A blood sample will be collected from you for pharmacogenetic testing. This test analyzes specific genes (CYP3A4, SLC6A4, HTR2A, CYP2D6, CYP2B6, and CYP2C19) that can affect how your body processes antidepressant medications. This genetic information has not been tested for you before.

2 Treatment assignment and medication initiation

Based on the study design, you will be assigned to one of two groups. One group will have antidepressant selection guided by the genetic test results along with your demographic, clinical, and other medication information. The other group will receive standard clinical care without genetic testing guidance.

Your treating physician will initiate a new antidepressant treatment following the failure of your previous therapy. The medication selected may be one of the following, taken by mouth: vortioxetine, escitalopram, sertraline, quetiapine, bupropion, clomipramine, venlafaxine, imipramine, fluoxetine, mianserin, duloxetine, agomelatine, amitriptyline, nortriptyline, fluvoxamine, mirtazapine, paroxetine, citalopram, trimipramine, or desvenlafaxine.

The specific medication, dosage, and frequency will be determined by your physician based on your individual clinical situation and, if applicable, your genetic test results. The medication will be provided in various forms such as tablets or capsules, depending on which antidepressant is selected.

3 Follow-up period and monitoring

You will be monitored for 16 weeks after starting the new antidepressant treatment. During this period, your depression symptoms will be regularly assessed using the PHQ-9 and MADRS questionnaires to evaluate whether your symptoms are improving or if remission has been achieved.

Throughout the 16-week period, any changes to your treatment will be recorded. These changes may include switching to a different antidepressant medication or adjusting the dose of your current medication (either increasing or decreasing it, beyond the usual starting adjustments).

All scheduled clinical visits will take place as planned. Any additional, unscheduled visits to your healthcare provider or psychiatric consultations will also be documented.

If you receive any psychological therapy sessions, such as cognitive behavioral therapy (a type of talk therapy that helps change negative thought patterns) or interpersonal therapy (a therapy focused on improving relationships and communication), these will be recorded.

Any side effects or adverse reactions you experience during the treatment will be monitored and documented. This includes common side effects as well as serious adverse events. Special attention will be given to specific concerns such as suicidal thoughts, suicide attempts, serotonin syndrome (a potentially serious condition caused by too much serotonin in the body), and neuroleptic malignant syndrome (a rare but serious reaction to certain medications).

If you require hospitalization for any reason during the study period, this will be recorded.

If you are a woman of childbearing potential, you will need to continue using highly effective contraception or practice sexual abstinence throughout the study to avoid pregnancy.

4 End of follow-up assessment

At the end of the 16-week follow-up period, a final assessment will be conducted to determine whether your depression symptoms have achieved remission. This will be measured using the same PHQ-9 and MADRS questionnaires used at the beginning of the study.

All information collected during the study, including the number of treatment adjustments, clinical visits, therapy sessions, hospitalizations, and any adverse events, will be compiled for analysis.

Who Can Join the Study?

You must be able to understand the purpose of the study and its risks, give your permission to participate, and allow your health information to be used according to privacy laws.
You must voluntarily sign a consent form, which is a document showing you agree to take part in the study.
You must be 18 years of age or older when you sign the consent form.
You must be willing and able to participate in the study and attend most of the required visits.
You must be experiencing your first episode of depression, which means this is the first time you have been diagnosed with depressive disorder, a condition that causes persistent feelings of sadness and loss of interest. This diagnosis must be confirmed by your doctor and recorded in your medical file.
You must currently be taking medication to treat your depression at the time you join the study, and you must have tried no more than one antidepressant treatment before, which is a type of medication used to treat depression.
Your depression symptoms must reach certain levels on two questionnaires: a score of 10 or higher on the PHQ-9, which is a questionnaire that measures depression symptoms, and a score of 18 or higher on the MADRS, which is another scale that assesses depression severity. Both must be measured within two weeks before joining the study.
You must not have had genetic testing before for specific genes called CYP3A4, SLC6A4, HTR2A, CYP2D6, CYP2B6, or CYP2C19, which are genes that can affect how your body processes certain medications.
If you are a woman who can become pregnant, you must agree to use very effective birth control methods or not have sexual intercourse during the study, and you must commit to not becoming pregnant during this time.

Who Cannot Join the Study?

The study does not list specific reasons why patients cannot participate
General exclusion criteria will be determined by the study doctors during screening
Your doctor will review your medical history and current health condition to decide if this study is right for you

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country	Status
Hospital Dr. R Lafora	Madrid	Spain
Centro de Salud Mental Fuencarral	Madrid	Spain

Other Sites

Site Name	City	Country
Hospital Universitario Puerta De Hierro De Majadahonda	Majadahonda	Spain
Fgtrkyqwa Pdcf Ls Iassxgxlntzhy Bxfififbp Dti Hltbvkaf Unwlgmpcwrbwf Lq Pbf	Madrid	Spain
Cejaum dm Smcyb Mrsfup Tdiypz	Madrid	Spain

Trial status

Country	Status	Recruitment Start
Spain	Not yet recruiting	19.01.2026

Trial locations

Investigated drugs:

Antidepressants are medications used to treat depression and other mood disorders. They work by affecting certain chemicals in the brain that influence mood and emotions. In this trial, doctors will select which antidepressant to prescribe based on either genetic testing results or standard medical practice. The goal is to find out if using genetic information helps doctors choose the most effective antidepressant for each patient, leading to better treatment outcomes.

Depressive Disorder – Depressive disorder is a mental health condition characterized by persistent feelings of sadness, emptiness, or loss of interest in activities that were once enjoyable. People with this condition often experience changes in sleep patterns, appetite, and energy levels. The disorder affects how a person thinks, feels, and handles daily activities. Symptoms must be present for at least two weeks and represent a change from previous functioning. The condition can vary in severity and may occur as single episodes or recur multiple times throughout a person’s life. Without appropriate intervention, symptoms can persist for months or even years, significantly impacting personal relationships, work performance, and overall quality of life.

Trial ID:

2025-522967-13-00

Protocol code:

PREDICT

Trial Phase:

Therapeutic confirmatory (Phase III)

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Testing a Pharmacogenetic-Guided Treatment Selection Strategy with Antidepressant Drug Combination for Patients with Depressive Disorder

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