Citalopram and Self Emotional Processing

The Effect of Acute Citalopram on Self-referential Emotional Processing and Social Cognition in Healthy Volunteers

This study is investigating the effect of an acute dose of citalopram on emotional processing about the self. Using a parallel-group double-blind design, participants will be randomised to receive either an acute dose of citalopram or placebo. Participants will then complete a number of widely used computer-based cognitive tasks measuring emotional processing biases towards the self.

This study has also been registered on OSF: https://osf.io/nhjvs/?view_only=b39c49bddfd543b99b627dc992e49b45

Study Overview

• Status: Unknown
• Conditions: Depressive Disorder; Depression; Molecular Mechanisms of Pharmacological Action; Mental Disorder; Cognition; Antidepressive Agents
• Intervention / Treatment: Drug: Citalopram; Drug: Placebo oral tablet

Detailed Description

Antidepressants are thought to operate by changing the way patients process emotional information. After a single dose of citalopram or fluoxetine healthy volunteers have been found to display an increased recognition of happy facial expressions and a reduced recognition of sad faces, in the absence of changes in mood. Studies using depressed participants have produced similar results. However, there has been comparatively little research on changes in emotional processing biases about the self following antidepressant administration. Sense of self has been proposed as fundamental for mental health, with self-schemas acting as a focus through which valence and reward influenced perception, memory and decision-making. Antidepressants may increase learning of positive information about the self, potentially remediating negative self-schema and subsequently reducing depression symptoms.

In this study, the investigators aim to examine whether acute administration of citalopram is associated with an increase in positive emotional learning biases about the self. Using a parallel-group double-blind design, participants will be randomised to receive either an acute dose of citalopram or placebo. Participants will then complete a number of widely used computer-based cognitive tasks measuring emotional processing biases. Identifying early changes in cognition and behaviour following antidepressant treatment will increase our knowledge of how antidepressants operate, and provide putative targets to identify early response to antidepressants.

This study has also been registered on OSF: https://osf.io/nhjvs/?view_only=b39c49bddfd543b99b627dc992e49b45

Starting from the 8th November 2019 an additional task (the Oxford Cognition Stress Task (OCST)) was included in the test battery. This task has been developed by the Psychopharmacology and Emotion Research Laboratory (PERL), Department of Psychiatry, University of Oxford. This is an acute psychosocial stress induction paradigm, comprised of computerised cognitive tasks with an induced failure component. An algorithm varies task timing/difficulty to be just beyond participants' ability, accompanied by aversive feedback. The OCST induces mild, transient increases in stress and arousal, as indexed by heart rate, skin conductance, salivary cortisol and self-reported subjective state measures. Data for this task will be collected, analysed and published by PERL and will not be included in any publications relating to the previous registration for this study. The OCST task has been included at the end of the test battery and is therefore not expected to influence data relating to any self-report measures or tasks outlined in the previous registration

This section of the study has been registered separately on ClinicalTrials.gov (titled 'Citalopram and Stress Reactivity') to reflect the separate research questions and study team involvement.

• Study Type: Interventional
• Enrollment (Anticipated): 44
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Catherine Hobbs, MSc; Phone Number: +44 01865618335; Email: c.hobbs@bath.ac.uk

Study Locations

• United Kingdom
  • Oxford, United Kingdom, OX3 7JX
    • Recruiting
    • University of Oxford

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or Female
• Aged 18 -45 years
• Fluent in written and spoken English at a sufficient level to understand and complete the tasks
• Body Mass Index (BMI) 18-30
• Participant is willing and able to give informed consent for participation in the study
• Not currently taking any regular medications (expect the contraceptive pill)

Exclusion Criteria:

• Any past or current Axis 1 DSM-V psychiatric disorder
• Current use of psychoactive medication (except the contraceptive pill, the Depo-Provera injection or the progesterone implant)
• Current or past history of drug or alcohol dependency
• History of current significant neurological condition (e.g. epilepsy)
• Known hypersensitivity to the study drug
• Currently pregnant or breast feeding
• Previous participation in a study that uses the same or similar computer tasks as those used in the present study
• Previous participation in a study that involves the use of a medication within the last three months
• Significant medical condition
• Smokers consuming > 5 cigarettes per day
• Individuals consuming > 6 caffeinated drinks per day
• Lactose Intolerance (due to the study involving administration of a lactose placebo tablet)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Citalopram; Single acute oral dose 20 mg Citalopram (tablet encapsulated in opaque capsule)	Drug: Citalopram; Single dose administration of citalopram (20mg)
PLACEBO_COMPARATOR: Placebo; Single acute oral dose Lactose Placebo (tablet encapsulated in opaque capsule)	Drug: Placebo oral tablet; Single dose administration lactose placebo tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Social Evaluation Learning Task: Bias Scores	An overall index of positive or negative bias will be calculated for each referential condition (self, friend, stranger) using errors to criterion (the number of errors made before 8 rule-congruent responses). Bias is calculated by subtracting errors to criterion made when learning the dislike rule from errors to criterion made when learning the like rule. A positive value indicates a negative bias, as fewer errors are made learning the dislike rule compared to the like rule. Conversely, a negative value indicates a positive bias, as fewer errors are made learning the like rule compared to the dislike rule. The minimum possible value is - 24 (complete bias towards being liked), and the maximum value is + 24 (complete bias towards being disliked).	Day 1: 3-5.5 hours post drug administration
Associative Learning Task: Reaction Times (ms)	Mean reaction times will be calculated for each referential condition (self, friend, stranger), reward condition (high, medium, low) and valence condition (positive, neutral, negative) for each respective task.	Day 1: 3-5.5 hours post drug administration
Associative Learning Task: Accuracy (% correct)	Mean accuracy will be calculated for each referential condition (self, friend, stranger), reward condition (high, medium, low) and valence condition (positive, neutral, negative) for each respective task.	Day 1: 3-5.5 hours post drug administration
Self-Esteem Go/No-Go Association Task: d'	Discriminative accuracy (d') will be calculated through applying Z-score transformations, and subtracting hit z-scores from false alarm z-scores. Z-scores are adjusted by adding or subtracting .005 if hit or false-alarm rates are 0 or 1. d' -values can then be compared for each possible categorical combination to examine implicit self-biases.	Day 1: 3-5.5 hours post drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prisoner's Dilemma: Cooperative Behaviours (%)	The main outcome for this task is the proportion of rounds on which participants choose to cooperate. The conditional probability of cooperating will be calculated according to the proportion of rounds on which participants cooperated following each of the four possible outcomes.	Day 1: 3-5.5 hours post drug administration
Prisoner's Dilemma: Reaction Times (ms)	Reaction times for cooperation versus non-cooperation choices will be calculated.	Day 1: 3-5.5 hours post drug administration
Emotional Categorisation and Recall: Number of words categorised	The mean number of positive and negative words categorised as describing or not describing the participant/the other will be recorded.	Day 1: 3-5.5 hours post drug administration
Emotional Categorisation and Recall: Hits	Mean hits will be collected for each referential condition and valence.	Day 1: 3-5.5 hours post drug administration
Emotional Categorisation and Recall: False Alarms	Mean alse intrusions will be collected for each referential condition and valence.	Day 1: 3-5.5 hours post drug administration

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: University of Bath
• Investigators: Principal Investigator: Katherine S Button, PhD, University of Bath

Publications and helpful links

Helpful Links

• PERL Oxford

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 11, 2019
• Primary Completion (ANTICIPATED): September 1, 2020
• Study Completion (ANTICIPATED): September 1, 2020

Study Registration Dates

• First Submitted: November 12, 2019
• First Submitted That Met QC Criteria: November 18, 2019
• First Posted (ACTUAL): November 19, 2019

Study Record Updates

• Last Update Posted (ACTUAL): November 19, 2019
• Last Update Submitted That Met QC Criteria: November 18, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Healthy Volunteers; Emotional Processing; Citalopram; Antidepressants; Self Processing
• Additional Relevant MeSH Terms: Pathologic Processes; Mood Disorders; Depressive Disorder; Disease; Mental Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Antidepressive Agents, Second-Generation; Citalopram
• Other Study ID Numbers: Acute_Citalopram

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: An anonymised dataset will be published as open access data on a secure online repository, such as Open Science Framework (https://osf.io/). Participant IDs will be randomly reassigned in this dataset to ensure complete removal of any linkage between anonymised and personal data. Self-report questionnaire data and task outcomes will be included.
• IPD Sharing Time Frame: An anonymised dataset will be shared after full anonymisation of study data and publication of findings. Data will be available indefinitely.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No