Citalopram and Stress Reactivity

The Effect of Acute Citalopram on Response to Acute Stress Induction

This study is investigating whether acute administration of citalopram is associated with a decrease in stress reactivity in healthy volunteers, compared to placebo administration. Using a parallel-group double-blind design, participants will be randomised to receive either an acute dose of citalopram or placebo. All participants will have come in for a screening visit. On the day of the research visit (following drug administration) participants will have completed a number of widely used computer-based cognitive tasks measuring emotional processing biases. They will then complete the Oxford Cognition Stress Task, a web-based acute stress induction paradigm, which is designed to induce mild transient increases in stress and arousal. Identifying early changes in stress reactivity following antidepressant treatment will increase the investigator's knowledge of how antidepressants operate, and provide putative targets to identify early response to antidepressants.

Study Overview

• Status: Unknown
• Conditions: Depressive Disorder; Depression; Stress; Mental Disorder; Cognition; Antidepressive Agents
• Intervention / Treatment: Drug: Citalopram; Other: Placebo

Detailed Description

In the Oxford Cognition Stress Task (OCST), participants are presented with a series of mental arithmetic, verbal (anagrams) and visuospatial (visual search) challenges on a computer screen. There is a time limit for completing each challenge, which is displayed on the screen as a time bar. To induce a high failure rate, the timing and difficulty of the challenges is automatically varied to ensure participants are correctly complete only 20-40% of the challenges within the time, and some of the verbal challenges (anagrams) are impossible to solve. Participants are given feedback on their performance on the screen which indicates that they are performing badly. Heart rate will be measured continuously during the OCST, and during pre- and post- task periods. Baseline and post-OCST measures of blood pressure and samples of saliva (for cortisol analysis) will be taken. Participants will also complete Visual Analogue Scales pre- and post-OCST to give a subjective measure of stress and mood. Participants will not be told the extent to which becoming stressed (and finding the task difficult) is intended. At the end of the test session, participants will be fully debriefed as to the nature of the OCST.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lucy Wright, MSc; Phone Number: +44 01865 613111; Email: lucy.wright@psych.ox.ac.uk

Study Locations

• United Kingdom
  • Oxford, United Kingdom, OX3 7JX
    • Recruiting
    • University of Oxford
    • Contact: Susannah Murphy, DPhil

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• 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) or medication which may affect the stress response (e.g. corticosteroids, beta-blockers)
• Current or past history of drug or alcohol dependency
• History of current significant neurological condition (e.g. epilepsy) or heart disease/hypertension
• 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 Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart rate (beats per minute)	Difference in heart rate during the Oxford Cognition Stress Task relative to pre-task baseline period between citalopram and placebo groups	Day 1: 4.5-5.5 hours post drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart rate variability (Root Mean Square Of Successive Differences: RMSSD)	Difference in RMSSD during the Oxford Cognition Stress Task relative to pre-task baseline period between citalopram and placebo groups	Day 1: 4.5-5.5 hours post drug administration
Salivary cortisol	Difference in salivary cortisol following the Oxford Cognition Stress Task relative to pre-task baseline between citalopram and placebo groups; difference in area under the curve for all study timepoints between citalopram and placebo groups	Day 1: 4.5-5.5 hours post drug administration
Blood pressure	Difference in systolic and diastolic blood pressure following the Oxford Cognition Stress Task relative to pre-task baseline between citalopram and placebo groups	Day 1: 4.5-5.5 hours post drug administration
Subjective measures of stress and arousal	Difference in state anxiety, positive and negative affect, and Visual Analogue Scale (VAS) ratings of stress (from 0 to 100, where 0 indicates 'Not at all' and 100 indicates 'Extremely') following the Oxford Cognition Stress Task relative to pre-task baseline between citalopram and placebo groups	Day 1: 4.5-5.5 hours post drug administration

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: University of Bath
• Investigators: Principal Investigator: Susannah Murphy, DPhil, University of Oxford

Publications and helpful links

Helpful Links

• PERL Oxford webpage

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 8, 2019
• First Submitted That Met QC Criteria: November 12, 2019
• First Posted (Actual): November 13, 2019

Study Record Updates

• Last Update Posted (Actual): November 15, 2019
• Last Update Submitted That Met QC Criteria: November 13, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Healthy volunteers; Citalopram; Stress induction paradigm
• 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: OCST_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 repository (Open Science Framework https://osf/io/).
• IPD Sharing Time Frame: Following full anonymisation of study data and publication of findings. Data will be stored indefinitely.
• IPD Sharing Supporting Information Type: Study Protocol; Informed Consent Form (ICF)

Drug and device information, study documents

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