Effects of Intravenous (IV) Citalopram Hydrochloride During Transcranial Magnetic Stimulation in Major Depressive Disorder (MDD)

NCT04846829 | Active Not Recruiting Early Phase 1 FDA Drug FDA Device

• 1 other identifier: 16-002086
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study will recruit 30 subjects diagnosed with Major Depressive Disorder (MDD). Subjects will be recieve one infusion treatment of citalopram or placebo and 10 treatments of a form of transcranial magnetic stimulation, theta burst stimulation (TBS). Subjects will also undergo brain scans, quantitative electroencephalography (qEEG) brain activity recordings, and mood surveys. Study activities will be performed over the course of 4 weeks.

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• Percent change in Hamilton Depression Scale

  A 17-item, clinician-administered depression assessment scale pertaining to symptoms of depression experienced over the past week. Each item is scored between 0-4 points. Scoring is based on the 17-item scale and scores of 0-7 are considered as being normal, 8-16 suggest mild depression, 17-23 moderate depression and scores over 24 are indicative of severe depression; the maximum score being 52 on the 17-point scale.

  through study completion, an average of 10 days

Secondary Outcomes (1)

• Percent. change in The Inventory of Depressive Symptomatology-Self Report

  through study completion, an average of 10 days

Study Arms (4)

Placebo infusion

PLACEBO COMPARATOR

Placebo comparator to active study drug

Drug: Placebo

intravenous citalopram hydrochloride (CIT)

ACTIVE COMPARATOR

A single 40 mg dose of CIT diluted in 60 cc normal saline will be delivered intravenously under double-blind conditions via pump over a 40-minute period.

Drug: intravenous citalopram hydrochloride (CIT)

intermittent Theta Burst Stimulation

EXPERIMENTAL

* 10 sessions of treatment with cTBS to right DLPFC * TBS consists of three TMS pulses given at 50 Hz, with this triplet repeated at a frequency of 5 Hz (every 200 ms). * iTBS paradigm of a 2 s train repeated every 10 seconds

Device: intermittent theta burst stimulation

continuous Theta Burst Stimulation

EXPERIMENTAL

* 10 sessions of treatment with iTBS to left or cTBS to right DLPFC * TBS consists of three TMS pulses given at 50 Hz, with this triplet repeated at a frequency of 5 Hz (every 200 ms). * 1800 pulses of cTBS will be delivered

Device: continuous theta burst stimulation

Interventions

Placebo DRUG

saline PBO will be administered intravenously using established clinical procedures. A single dose if saline PBO will be delivered intravenously under double-blind conditions via pump over a 40-minute period.

Placebo infusion

intermittent theta burst stimulation DEVICE

10 sessions of treatment with cTBS to right DLPFC TBS consists of three TMS pulses given at 50 Hz, with this triplet repeated at a frequency of 5 Hz (every 200 ms). iTBS paradigm of a 2 s train repeated every 10 seconds

intermittent Theta Burst Stimulation

intravenous citalopram hydrochloride (CIT) DRUG

CIT will be administered intravenously using established clinical procedures. A single 40 mg dose of CIT diluted in 60 cc normal saline will be delivered intravenously under double-blind conditions via pump over a 40-minute period.

intravenous citalopram hydrochloride (CIT)

continuous theta burst stimulation DEVICE

10 sessions of treatment with iTBS to left or cTBS to right DLPFC TBS consists of three TMS pulses given at 50 Hz, with this triplet repeated at a frequency of 5 Hz (every 200 ms). 1800 pulses of cTBS will be delivered

continuous Theta Burst Stimulation

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• years of age. MDD currently depressed subjects will meet DSM-V criteria for MDD based on the Mini-International Neuropsychiatric Interview (MINI) (http://www.medicaloutcomes.com/index/mini7fororganizations) with a 17-item Hamilton Depression Rating Scale (HamD17) (Hamilton, 1960) score \> 17.
• Subjects must have failed to enter remission with at least two prior antidepressant medications in the current episode (Vasavada et al., 2016)
• Must have been free of any medications known to significantly affect brain function for at least ten days prior to enrollment (except fluoxetine, which will require a five-week washout).

You may not qualify if:

• No unstable medical illness that would prevent completion of participation in the trial (determined as needed from physical examination, ECG, laboratory safety tests, as well as a review of systems).
• Clinically significant physical abnormalities as indicated by physical examination, hematological laboratory assay, or urinalysis, defined as:
• hematology and chemistry laboratory tests that are within normal (+/- 10%) limits with the following exceptions: a) liver function tests (total bilirubin, ALT, AST, and alkaline phosphatase) \< 3 x the upper limit of normal, and b) kidney function tests (creatinine and BUN) \< 2 x the upper limit of normal;
• A screening ECG that demonstrates anything other than normal sinus rhythm, normal conduction, and no clinically significant arrhythmias
• History of epilepsy, seizures, or severe head trauma;
• Resting vital signs on any study visit outside of acceptable parameters (i.e., pulse of 60-100 bpm, blood pressures of 90-150 mm Hg systolic, 50- 90 mm Hg diastolic);
• Any indication of suicidal ideation (e.g. as assessed by the suicidality question on the HamD17or the Columbia Suicide Severity Rating Scale.
• Baseline QT prolongation (QTc\> 450 ms): Given that citalopram has been found to be associated with a dose-dependent risk of ECG QT interval prolongation, in order to avoid the potential risk of causing ventricular arrhythmias including Torsades de Pointes, we will exclude participants from the study who exhibit baseline QTc prolongation.
• For women of childbearing age, a positive urine pregnancy test, as well as women who are currently breastfeeding or not using a medically acceptable method of birth control
• Presence of any implanted medical device or metal in the body that would render it unsafe to perform TMS or an MRI.
• Axis I: the presence of any other primary mood, anxiety, or psychotic disorder, depression secondary to a general medical condition, or substance- induced illness. Subjects also will be excluded if they have current suicidal intent or plan, a history of substance abuse or dependence within the past six months (except nicotine and caffeine), Bipolar Disorder or psychotic disorder (lifetime), eating disorder (current or within the past year), Obsessive Compulsive Disorder (lifetime), Post-Traumatic Stress Disorder (PTSD, current or within the past year);
• Axis III: active medical illness known to significantly affect brain function or that could be etiologically related to the ongoing depression (e.g., untreated hypothyroidism);
• Current treatment with a medication known to affect brain function. This would include both psychiatric and centrally-acting neurological agents.
• The investigators have chosen to exclude these subjects because current medication could affect measures of brain function as well as introduce an uncontrolled treatment effect into the study. Prospective subjects who are currently taking psychiatric medications will also be excluded as the risk of antidepressant discontinuation outweighs the potential benefit of study participation. A history of prior treatment with IV CIT. We have chosen to exclude subjects who have received this treatment because they may have a degree of treatment resistance that would make it less likely for them to respond to treatment in the current protocol. Additionally, if they previously have received CIT the PBO treatment blind in the current protocol may not be effective;
• Current treatment with a medication known to affect brain function. We have chosen to exclude these subjects because current medication could affect measures of brain function as well as introduce an uncontrolled treatment effect into the study. These medications include: antidepressants, barbiturates, anticonvulsants/mood stabilizers, benzodiazepines, anticholinergics, herbal preparations, antipsychotics, muscle relaxants, antimigraine, psychostimulants, anti-Parkinsonian medications, sedating antihistamines, corticosteroids (oral; topical preparations OK), Zyban (bupropion for use in smoking cessation);

Sponsors & Collaborators

• University of California, Los Angeles: lead

Study Sites (1)

UCLA Depression Research and Clinic Program

Los Angeles, California, 90024, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 12, 2021
• First Posted: April 15, 2021
• Study Start: April 24, 2017
• Primary Completion (Estimated): April 24, 2028
• Study Completion (Estimated): April 24, 2028
• Last Updated: September 22, 2025

Record last verified: 2025-09

Locations

US (1)