Effects of Intravenous (IV) Citalopram on Emotional Brain Activity in Healthy Young and Elderly Adults

Pharmacodynamics of Intravenous Citalopram in the Elderly: a Functional Magnetic Resonance Imaging Analysis

Antidepressant medications known as selective serotonin reuptake inhibitors (SSRIs) are most commonly prescribed to treat depression and anxiety. How antidepressants work on the brain to alter mood and behaviour is not well understood. This study will use a brain scanning technique (functional magnetic resonance imaging) to examine how aging impacts brain activation during emotional tasks after the administration of intravenous (IV) citalopram (this is the only SSRI available in this form, and is well tolerated and safe in young and old adults). The investigators will further determine what role genetic differences play in this relationship. The investigators expect to see an increase in brain signal as the concentration of IV citalopram increases. However, the investigators propose that the brain signal in older adults will not be as strong as in younger adults. Furthermore, the investigators expect that participants genetically predisposed to have fewer serotonin transporters (the site of action of SSRIs) will show greater decreases in brain activation with citalopram.

Study Overview

• Status: Terminated
• Conditions: Healthy Young and Elderly Volunteers
• Intervention / Treatment: Drug: Intravenous Citalopram; Drug: Normal Saline

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M6A2E1
      • Rotman Research Institute at Baycrest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male aged 60 or older (elderly group)
• Male aged 20-40 (younger adult group)
• English speaking
• Right-handed
• Non-smoker
• Score of 27 or greater on the Mini Mental State Exam

Exclusion Criteria:

• Unstable medical, cardiac, or neurological illness (including stroke, brain tumour, epilepsy, significant head injury, Alzheimer's, Parkinson's or Huntington's disease)
• Laboratory results indicating unanticipated illness or intolerability of blood drawing procedures or of study drug
• Current or lifetime Axis-I psychiatric diagnosis on the DSM-IV/SCID (i.e., Module A: Mood, Module F: Anxiety, Module B & C: Psychosis)
• History of drug or alcohol abuse within one year, or lifetime history of alcohol or drug dependence (i.e., SCID Module E: Substance Abuse, or clinically significant urine toxicology screen)
• History of non-tolerance to SSRI therapy; including history of SSRI-related syndrome of inappropriate antidiuretic hormone secretion (SIADH) or sinus bradycardia on ECG (less than 50 beats per minute)
• Contraindication to MRI (as per MRI Contraindication Screening Form)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intravenous Citalopram	Drug: Intravenous Citalopram; Single dose of 20mg parenteral citalopram diluted in 250mL of 0.9% sodium chloride solution, infused over 30 minutes
Placebo Comparator: Normal Saline; 250mL of 0.9% Sodium Chloride Solution	Drug: Normal Saline; Single dose of 250mL of 0.9% sodium chloride solution, infused over 30 minutes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BOLD fMRI Response	Changes in affect-related neuronal activation as measured by blood oxygenation level-dependent (BOLD) fMRI response to IV citalopram are the primary outcome measures. Imaging data will be compared between IV citalopram and placebo administration and young and old adults.	Visit 1, Visit 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genetics and Cognitive/Emotional Change	Secondary measures include analysis of the relationship between 5HTT polymorphism and neuronal activation, and changes in cognitive and emotional assessments between IV citalopram and placebo.	Visit 1, Visit 2

Collaborators and Investigators

• Sponsor: Rotman Research Institute at Baycrest
• Collaborators: Centre for Addiction and Mental Health; University of Toronto
• Investigators: Principal Investigator: Bruce G Pollock, MD PhD FRCPC, Centre for Addiction and Mental Health

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: October 6, 2010
• First Submitted That Met QC Criteria: October 6, 2010
• First Posted (Estimate): October 7, 2010

Study Record Updates

• Last Update Posted (Actual): March 11, 2020
• Last Update Submitted That Met QC Criteria: March 9, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Elderly; Pharmacokinetics; Functional Magnetic Resonance Imaging; fMRI; Pharmacodynamics; Amygdala; Citalopram
• Additional Relevant MeSH Terms: 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: 08-39