Dimensional Approach to Evaluate Reward Processing in Major Depressive Disorder Pre- and Post-Desvenlafaxine Treatment

A Dimensional Approach to Evaluate Reward Processing in Major Depressive Disorder Before and After Treatment With Desvenlafaxine

Anhedonia (the lack of pleasure in normally pleasurable things) is a common symptom of major depressive disorder (MDD), and it may impact how patients with depression experience reward. Understanding how anhedonia is related to the experience of reward may help improve how depression is treated. Computer tasks can be used to measure how reward is experienced, and these measures might be able to predict things like who is likely to become depressed, or who will respond to antidepressant medication. Studying the relationship between anhedonia and reward in patients with depression might also tell us something about how to improve diagnosis and treatment of other psychiatric disorders.This is an open label controlled treatment study lasting 8 weeks. The brain scans will be used to find changes in brain areas that may be related to how people perform on the tasks. The investigators goal is to use this information to help us find a reliable predictor that can be used to guide MDD treatment.

Study Overview

• Status: Completed
• Conditions: Depression; Anhedonia
• Intervention / Treatment: Drug: Desvenlafaxine

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5B 1M8
      • St. Michael's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion/exclusion criteria for MDD patients (n=40) are as follows:

Inclusion Criteria

1. DSM-5 criteria for Major Depressive Episode (MDE) within a MDD, confirmed through MINI diagnosis
2. Age between 18 and 60 years
3. Hamilton Depression Rating Scale - 17 item (HRSD-17)58 > 17 (moderate to severe symptoms)
4. Free of psychotropic medications for at least 5 half-lives before baseline visit
5. Ability to undergo MRI scanning (absence of metal, pacemakers, etc.)

Exclusion Criteria

1. Pregnancy/lactation
2. Medical condition requiring immediate investigation or treatment
3. Recent (< 6 months)/current history of drug abuse/dependence (other than caffeine, or nicotine)
4. Lifetime history of psychosis, other Axis I comorbidities are allowable
5. Significant Axis II diagnosis
6. Previous intolerance or failure to respond to an adequate trial of desvenlafaxine
7. Failure of > 2 antidepressant treatments of adequate dose and duration for current MDE

Inclusion/exclusion criteria for Healthy Controls (n=20) are as follows:

Inclusion Criteria

1. Age between 18 and 60 years
2. Ability to undergo MRI scanning (absence of metal, pacemakers, etc.)

Exclusion Criteria

1. Pregnancy/lactation
2. Medical condition requiring immediate investigation or treatment
3. Lifetime history of any psychiatric disorder
4. Lifetime history of receiving an antidepressant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treatment; Patients in this arm will receive treatment with desvenlafaxine for 8 weeks.	Drug: Desvenlafaxine; Patients will be provided 50mg dose of desvenlafaxine for 1 week titrated up to 100mg dose of desvenlafaxine for 7 weeks.; Other Names: Pristiq
No Intervention: Healthy Control; Patients in this arm are healthy controls and will not receive any medication.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measuring Reward association and valuation using the Reward Association Task	Based on signal detection theory, it evaluates response bias as a function of prior reward and permits an objective assessment of disorder-related sensitivity to reward. To evaluate the how the 6 facets of reward are related to each other in unmedicated MDD patients in order to develop a clearer understanding of reward pathways	Change from Baseline at 8 Weeks
Measuring Expectation using a prediction error task, to measure learning and choosing, during functional Magnetic Resonance Imaging (fMRI)	This distinction was included in the design in order to dissociate potentially different neural circuits subserving learning reward associations and using them to guide behavior. To evaluate the how the 6 facets of reward are related to each other in unmedicated MDD patients in order to develop a clearer understanding of reward pathways	Change from Baseline at 8 Weeks
Anticipation of reward using the monetary incentive delay during fMRI	This task was designed to disentangle anticipatory vs. consummatory phases of reward processing. To evaluate the how the 6 facets of reward are related to each other in unmedicated MDD patients in order to develop a clearer understanding of reward pathways	Change from Baseline at 8 Weeks
Motivation/effort using the Cued-Reinforcement Reaction Time Task and the EEfRT task.	The Cued-Reinforcement Reaction Time Task (CRRT) provides an evaluation of reward-based reaction time speed as an index of incentive motivation.The EEfRT task allows analysis of the predictive value of reward probability and magnitude on effort-based decision making. To evaluate the how the 6 facets of reward are related to each other in unmedicated MDD patients in order to develop a clearer understanding of reward pathways	Change from Baseline at 8 Weeks
Pleasure/Liking using the monetary incentive delay task in an fMRI	This task was designed to disentangle anticipatory vs. consummatory phases of reward processing. To evaluate the how the 6 facets of reward are related to each other in unmedicated MDD patients in order to develop a clearer understanding of reward pathways. To evaluate the how the 6 facets of reward are related to each other in unmedicated MDD patients in order to develop a clearer understanding of reward pathways	Change from Baseline at 8 Weeks
Feedback integration using the Probabilistic Reversal Learning task during fMRI	participants are presented with a choice of two stimuli. Based on their first choice, the selected stimulus will be rewarded with a high probability, while the other will be rewarded with a low probability.To evaluate the how the 6 facets of reward are related to each other in unmedicated MDD patients in order to develop a clearer understanding of reward pathways	Change from Baseline at 8 Weeks

Collaborators and Investigators

• Sponsor: Unity Health Toronto
• Investigators: Principal Investigator: Sakina Rizvi, PhD, Unity Health Toronto

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2017
• Primary Completion (Actual): November 4, 2019
• Study Completion (Actual): November 4, 2019

Study Registration Dates

• First Submitted: July 15, 2016
• First Submitted That Met QC Criteria: August 3, 2016
• First Posted (Estimate): August 8, 2016

Study Record Updates

• Last Update Posted (Actual): November 2, 2020
• Last Update Submitted That Met QC Criteria: October 28, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Mood Disorders; Neurologic Manifestations; Neurobehavioral Manifestations; Depressive Disorder; Anhedonia; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Serotonin and Noradrenaline Reuptake Inhibitors; Desvenlafaxine Succinate
• Other Study ID Numbers: DVS-01

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No