Pharmacogenetic-Based Dosing of Sertraline, Aripiprazole, Risperidone, and Escitalopram in Mood, Anxiety, and Psychotic Disorders: A Comparative Study

The primary objective of this study is to compare **individualised medication dosing** based on pharmacogenetics in psychiatric patients with standard dosing practices. This is clinically relevant as it aims to optimize treatment efficacy and minimize adverse effects in patients with mood disorders, anxiety disorders, and psychotic disorders, including major depressive disorder, bipolar disorder, panic disorder, social phobia, specific phobia, agoraphobia, generalized anxiety disorder, schizophrenia, and schizoaffective disorder.

Secondary objectives include:

• Evaluation of the impact of pharmacogenetic testing on clinical response, side effects, general wellbeing, and psychosocial functioning.
• Deep phenotyping of patients during the clinical trial to identify other factors besides pharmacogenetics that may influence individual medication response, including passive monitoring of behavioral aspects via a mobile phone application.
• Investigation of other genetic factors related to medication response, including genetic variants associated with drug absorption, distribution, metabolism, and elimination.

The clinical trial involves a study population comprising both **male** and **female** participants aged between 18 and 64 years. The trial focuses on individuals diagnosed with **mood disorders** such as major depressive disorder and bipolar disorder (currently in a depressive episode), **anxiety disorders** including panic disorder, social phobia, specific phobia, agoraphobia, and generalized anxiety disorder, as well as **psychotic disorders** like schizophrenia and schizoaffective disorder. Participants are required to have experienced an inadequate response to at least one psychotropic treatment in their lifetime and are currently undergoing psychiatric treatment, either as inpatients or outpatients. The trial includes individuals who are switching to specific medications due to inadequate response or intolerance to previous treatments. Women of child-bearing potential must have a negative pregnancy test and agree to use highly effective contraceptive methods during the study. The sponsor has not provided information regarding the total number of participants in the trial.

The clinical trial is designed to evaluate the efficacy of individualized medication dosing based on pharmacogenetics in patients with psychiatric conditions, compared to standard dosing practices. The trial employs a **randomized**, **double-blind**, and **controlled** design to ensure the reliability and validity of the results. The study will span a total duration of 24 weeks, with participant involvement expected to last the same period, barring any conditions that necessitate early termination, such as adverse events or non-compliance with study protocols.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as a diagnosis of mood disorder, anxiety disorder, or psychotic disorder, as per DSM-5 criteria. This visit will also involve obtaining informed consent and conducting baseline assessments. Follow-up visits will occur at regular intervals to monitor treatment response, side effects, and overall well-being using standardized scales such as the Hamilton Depression Scale (SIGH-D), Hamilton Anxiety Scale (SIGH-A), and the Positive and Negative Symptom Scale (PANSS). The primary endpoint is patient recovery at 24 weeks, assessed using the Recovery Assessment Scale (RAS, RAS-DS).

Secondary endpoints include evaluations of well-being, quality of life, psychosocial functioning, clinical symptomatology, and side effects over the 24-week period. The end-of-study visit will involve a comprehensive assessment to determine the final outcomes of the trial. Participants may be withdrawn from the study if they experience significant adverse effects, fail to adhere to the study protocol, or choose to withdraw consent. The trial aims to provide evidence on the benefits of pharmacogenetic-guided dosing in improving treatment outcomes for psychiatric patients.

The clinical trial involves the administration of several **experimental medications** to evaluate the efficacy of individualized medication dosing based on pharmacogenetics in psychiatric patients. The first medication, **Sertraline**, is provided in the form of a film-coated tablet. The active substance, sertraline, is of chemical origin. The maximum daily dose is 150 mg, with a total maximum dose of 25.2 grams over the treatment period. The medication is administered orally, and the treatment period extends up to 24 weeks. Participant compliance is monitored through regular assessments to ensure adherence to the dosing schedule.

**Aripiprazole** is another medication used in the trial, available in tablet form. The active substance, aripiprazole, is also of chemical origin. The maximum daily dose is 30 mg, with a total maximum dose of 5.04 grams over the treatment period. This medication is administered orally, with a treatment duration of up to 24 weeks. Compliance monitoring is conducted to ensure participants adhere to the prescribed dosing regimen.

The trial also includes **Risperidone**, provided as a film-coated tablet. The active substance, risperidone, is chemically derived. The maximum daily dose is 6 mg, with a total maximum dose of 1 gram over the treatment period. Administration is oral, and the treatment period is up to 24 weeks. Participant adherence to the dosing schedule is monitored throughout the trial.

Lastly, **Escitalopram** is administered in the form of a film-coated tablet. The active substance, escitalopram, is of chemical origin. The maximum daily dose is 20 mg, with a total maximum dose of 3.36 grams over the treatment period. The medication is taken orally, with a treatment duration of up to 24 weeks. Compliance is monitored to ensure participants follow the dosing schedule accurately.

In addition to the experimental medications, standard-of-care therapy may be provided as necessary, and participant compliance with all treatments is closely monitored to ensure the integrity of the trial data.

Efficacy in this clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint is patient recovery at 24 weeks, evaluated through the patient recovery assessment scale (RAS, RAS-DS). Secondary endpoints include assessments of well-being and quality of life using the EuroQol 5 Dimensions-5 levels questionnaire (EQ-5D-5L), psychosocial functioning via the Functioning Assessment Short Test (FAST), and clinical symptomatology measured by the Structured Interview Guide for the Hamilton Depression Scale (SIGH-D) for mood disorders, the Structured Interview Guide for the Hamilton Anxiety Scale (SIGH-A) for anxiety disorders, and the Positive and Negative Symptom Scale (PANSS) for psychotic disorders. Additionally, side effects will be monitored using the Frequency, Intensity and Burden of Side Effects Ratings (FIBSER) and the Udvalg for Kliniske Undersogelse – Side Effects Rating Scale (UKU-SERS).

The efficacy parameters will be collected over a 24-week period. The assessments will be conducted at specified intervals to ensure comprehensive data collection and analysis. The tools and instruments used for these assessments are validated scales that are widely recognized in clinical research. The trial aims to compare individualized medication dosing based on pharmacogenetics with standard dosing practices in psychiatric patients, focusing on those with **major depressive disorder**, bipolar disorder, anxiety disorders, and psychotic disorders. The trial is designed to be low-intervention, with the investigational medicinal products being authorized and their use supported by scientific evidence, ensuring minimal additional risk to participants.