Investigation of Genetic Predictors of the Response to Selective Serotonin Re-uptake Inhibitors (SSRI) Treatment

Investigation of Genetic Predictors of the Response to SSRI Treatment

The antidepressant medications are among the most commonly prescribed pharmacological agents in patients with mood and anxiety disorder. Despite recent advances in antidepressant pharmacotherapy, there is a pressing need for substantial optimization and improvment of outcome of pharmacotherapy of psychiatric disorders by providing individualized and science-based treatment guidelines. Besides it is rather difficult in clinical practice to predict, which patient will response to a certain pharmacological treatment well and which one less so. Putative predictors of response to antidepressant include demographic and clinical characteristics, personality traits, biological markers and psychophysiological features. Recently the research studies shown that divergences in antidepressant efficacy may be related to genetic variations of patients. The pharmacogenetic studies have multiplied in recent decade due to the impact that such studies may have in everyday clinical practice once reliable predictors could be identified. The pharmacogenetic research using new DNA microarray-based technology can reasonably be expected to contribute to the prediction of likelihood of treatment response and risk of development of adverse side effects in individual patients in case of antidepressant treatment. By reducing costly treatment failures and the likelihood of serious adverse events, pharmacogenetic testing may help to improve the treatment possibilities for chronic diseases, reduce the burden prescription drug costs, and lower the costs of drug development. The further detailed investigation of peripheral gene expression profiles may help to identify responsible genes that underlie the process of development of affective disorders and open novel horizons for understanding molecular mechanisms of psychopharmacological treatment.

Study Overview

• Status: Completed
• Conditions: Major Depression
• Intervention / Treatment: Drug: escitalopram; Drug: bupropion

Detailed Description

To participate in the study the subjects must be at least 18 years old and give a written informed consent after an oral and written explanation of the study aims and methods. The study sample will include the female and male patients with panic disorder or major depression diagnosis according to DSM-IV criteria. Patients will be recruited from the out- and inpatients services of the Psychiatric Clinic of the Tartu University Hospital. For the detailed assessment of clinical severity of specific disorder and treatment effects the disorder-specific rating scales: Montgomery-Asberg's Depression Rating Scale (MADRS), Clinical Global Impression scale (CGI) will be used. The adverse effects will be evaluated by letting the patients to fill the checklist of side-symptoms. In both patient groups (with panic disorder and major depression) an SSRI escitalopram (Cipralex) will be administrated for 12 weeks in flexible dose ranging between 10 - 20 mg/per day. At the end of week 12 the patients will defined as responders if the decrease in MADRS scores is at least 50% and score on the CGI improvement scale is 2 or less. The remitters will defined if the scores are less than 12 on the MADRS. Patients who do not meet these criteria will defined as non-responders and non-remitters respectively. Depressive patients, showing non-response to escitalopram monotherapy will given the combination of 20 mg of escitalopram and 150-300 mg of bupropion (Wellbutrin SR) for 6 weeks.

• Study Type: Interventional
• Enrollment (Actual): 135
• Phase: Phase 4

Contacts and Locations

Study Locations

• Estonia
  • Tartu, Estonia, 50417
    • Department of Psychiatry, University of Tartu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Both genders
• Diagnosis according to DSM-IV criteria
• At severity of depression of at least moderate as indicated by a Montgomery-Asberg's Depression Rating Scale (MADRS) total score of 22 or higher
• Only secondary current comorbid anxiety disorder

Exclusion Criteria:

• Bipolar disorder
• Psychotic disorder or features
• Current eating disorders
• Mental retardation
• Any pervasive developmental disorder or cognitive disorder
• Alcohol or drug abuse-related disorders within 12 months prior to baseline
• Acute infections, neurological or any other unstable general disorders, serious suicide risk, formal behaviour therapy, or systematic psychotherapy, pregnancy or breastfeeding
• A history of hypersensitivity or non-response to escitalopram or bupropion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Escitalopram bupropion open-label; No comparator	Drug: escitalopram; escitalopram 10-20mg per day 12 weeks; Other Names: Cipralex; Drug: bupropion; bupropion 150-300mg per day 6 weeks; Other Names: Wellbutrin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montgomery-Asberg's Depression Rating Scale	Ten-item diagnostic questionnaire to measure the severity of depressive symptoms. The lowest possible score on the scale is 0 and the highest possible score is 60. The lowest possible score on the scale represents "the lack of any depressive symptoms" and the highest score represents the "severe depressive symptoms".	the results are for a single time point (12 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hamilton Rating Scale for Depression	17-item diagnostic questionnaire to measure the severity of depressive symptoms. The lowest possible score on the scale is 0 and the highest possible score is 52. The lowest possible score on the scale represents "the lack of any depressive symptoms" and the highest score represents the "severe depressive symptoms".	The outcome was measured at the week 12

Collaborators and Investigators

• Sponsor: University of Tartu
• Investigators: Principal Investigator: Eduard Maron, MD, PhD, Department of Psychiatry, University of Tartu

Publications and helpful links

Helpful Links

• State Agency of Medicines
• Department of Psychiatry
• University of Tartu

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): January 1, 2008
• Study Completion (Actual): January 1, 2008

Study Registration Dates

• First Submitted: February 2, 2009
• First Submitted That Met QC Criteria: April 24, 2019
• First Posted (Actual): April 25, 2019

Study Record Updates

• Last Update Posted (Actual): April 25, 2019
• Last Update Submitted That Met QC Criteria: April 24, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Safety; Treatment efficacy
• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Dopamine Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Dopamine Uptake Inhibitors; Citalopram; Bupropion
• Other Study ID Numbers: 2007-002649-19; 7043 (CTEP); SF0180125s08 (Other Grant/Funding Number: Ministry of Education, Estonia)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No