IV Citalopram + TMS for Depression

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of California, Los Angeles

Must not be taking: Antidepressants, Antipsychotics, Anticonvulsants, others

Disqualifiers: Epilepsy, Suicidal ideation, Bipolar, others

Compensation: Varies

Number of Visits: 10

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for Major Depressive Disorder (MDD) by combining a single infusion of citalopram with a series of transcranial magnetic stimulation (TMS) sessions. TMS, a non-invasive procedure, uses magnetic fields to stimulate brain nerve cells, potentially improving depression symptoms. Participants will receive either citalopram or a placebo and undergo 10 TMS sessions over four weeks. The trial seeks individuals diagnosed with depression who have not found relief with at least two other antidepressant medications during their current depressive episode. As an Early Phase 1 trial, this research aims to understand how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any medications that significantly affect brain function at least ten days before joining the trial, except for fluoxetine, which requires a five-week break. This includes antidepressants, anticonvulsants, and other similar medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that citalopram, a medication for depression, is generally well-tolerated. The FDA has approved it for treating depression in adults. When administered through an infusion, citalopram is tolerated as well as when taken orally, suggesting the infusion method is likely safe.

For intermittent theta burst stimulation (iTBS), studies indicate it is safe and effective. The FDA has approved iTBS for treating major depression. Research suggests that the safety and effectiveness of iTBS are comparable to other brain stimulation treatments for depression.

Overall, both treatments have a good safety record. However, since this is an early-phase trial, the researchers are focusing on the safety and tolerability of these treatments when used together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for depression because they combine advanced techniques to potentially enhance therapeutic effects. Unlike typical oral antidepressants like SSRIs, which can take weeks to show effects, intravenous citalopram may offer faster results by directly entering the bloodstream. Additionally, combining this with intermittent Theta Burst Stimulation (iTBS), a form of transcranial magnetic stimulation, targets specific brain regions with precision, potentially offering a quicker and more effective response. This novel approach could provide significant benefits for those who haven't responded well to traditional therapies.

What evidence suggests that this trial's treatments could be effective for depression?

Research has shown that administering citalopram through an IV can help treat severe depression. In this trial, some participants will receive intravenous citalopram, which studies have found to be more effective than a placebo, with many experiencing significant improvement. Other participants will receive intermittent theta burst stimulation (iTBS). Research suggests iTBS can quickly and effectively reduce depression symptoms, potentially offering greater efficiency and effectiveness than traditional treatments. Both treatments have shown promise in improving mood for people with major depressive disorder. ^{2 3 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults aged 21-55 with Major Depressive Disorder who haven't responded to at least two antidepressants and have a HamD17 score > 17. Participants must not have taken certain brain-affecting medications recently, except fluoxetine which requires a longer washout period. Those with unstable medical conditions, abnormal ECGs, or metal implants unsafe for MRI/TMS are excluded.

Inclusion Criteria

I haven't taken any brain-affecting meds for 10 days, except fluoxetine which I stopped 5 weeks ago.

I am between 21 and 55 years old.

I have been diagnosed with major depression and scored over 17 on a depression scale.

Exclusion Criteria

I haven't taken antidepressants, anticonvulsants, or similar medications in the last 30 days.

I have had ECT in the last 6 months or TMS did not help my depression.

I am not taking any medications from a specific list, except for topical corticosteroids.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single infusion of citalopram or placebo and 10 sessions of theta burst stimulation over two weeks

2 weeks

10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Citalopram Hydrochloride
• Intermittent Theta Burst Stimulation
• Placebo

Trial Overview The study tests the effects of IV citalopram hydrochloride versus placebo when combined with theta burst stimulation (TBS), a type of transcranial magnetic stimulation (TMS), on individuals with MDD. Over four weeks, participants will receive one infusion treatment and ten TBS treatments alongside mood surveys and brain activity assessments.

How Is the Trial Designed?

Group I: intermittent Theta Burst Stimulation Experimental Treatment 1 Intervention

* 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

Group II: continuous Theta Burst Stimulation Experimental Treatment 1 Intervention

* 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

Group III: intravenous citalopram hydrochloride (CIT) Active Control 1 Intervention

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.

Group IV: Placebo infusion Placebo Group 1 Intervention

Placebo comparator to active study drug

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

Published Research Related to This Trial

Intermittent theta burst stimulation (iTBS) is as effective as standard high-frequency (10 Hz) rTMS for treating treatment-resistant depression, showing non-inferiority in improving depression scores over 4-6 weeks in a study with 414 participants.

Both iTBS and 10 Hz rTMS had similar safety profiles and dropout rates, with headaches being the most common side effect, indicating that iTBS can be a viable alternative that allows for more patients to be treated in a shorter time without losing effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. Blumberger, DM., Vila-Rodriguez, F., Thorpe, KE., et al.[2022]

Intermittent theta burst stimulation (iTBS) and high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) are equally effective and safe for treating patients with treatment-resistant major depressive disorder, based on a comprehensive meta-analysis.

iTBS may be a more practical option in clinical settings because it requires less stimulation intensity and shorter treatment times compared to HF-rTMS, making it potentially more accessible for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent theta burst stimulation vs. high-frequency repetitive transcranial magnetic stimulation for major depressive disorder: A systematic review and meta-analysis. Kishi, T., Sakuma, K., Matsuda, Y., et al.[2023]

In a study of 27 participants, a prolonged intermittent theta burst stimulation (piTBS) protocol using 1,800 pulses showed limited effectiveness for major depressive disorder, with only 18.2% of participants achieving a response and 9.1% reaching remission.

Safety and tolerability were concerns, as 18.5% of participants experienced issues, suggesting that while piTBS is a promising approach, further research is needed to optimize its parameters and improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged intermittent theta burst stimulation in the treatment of major depressive disorder: a case series. Richard, M., Noiseux, C., Desbeaumes Jodoin, V., et al.[2022]

In a study of 26 patients with bipolar depression, active intermittent theta burst stimulation (iTBS) showed a high response rate of 72% and a remission rate of 42%, indicating its potential efficacy in treating this condition.

No adverse events were reported, demonstrating that iTBS is safe and well-tolerated, but further research with larger sample sizes is needed to confirm its superiority over sham treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Twice-daily neuronavigated intermittent theta burst stimulation for bipolar depression: A Randomized Sham-Controlled Pilot Study. Bulteau, S., Beynel, L., Marendaz, C., et al.[2020]

A clinical trial involving 96 outpatients with moderate depression will investigate the effectiveness of intermittent theta burst stimulation (iTBS) on reducing depressive symptoms, comparing it to a sham treatment over ten sessions.

The study will also explore various factors, including genetic and neuropsychological measures, that may influence the response to iTBS, ensuring a thorough safety screening and adherence to ethical guidelines throughout the trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The antidepressant effect of intermittent theta burst stimulation (iTBS): study protocol for a randomized double-blind sham-controlled trial. Ørbo, MC., Grønli, OK., Larsen, C., et al.[2023]

Intermittent theta-burst stimulation (iTBS) and high-frequency rTMS (HF-rTMS) show similar efficacy in treating treatment-resistant depression (TRD), with response rates of 48.0% for iTBS and 45.5% for HF-rTMS based on two high-quality randomized controlled trials involving 474 participants.

Both iTBS and HF-rTMS have comparable safety profiles, with similar rates of discontinuation and adverse events, such as headaches, indicating that iTBS is a safe alternative to HF-rTMS for patients with TRD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of intermittent theta burst stimulation versus high-frequency repetitive transcranial magnetic stimulation for patients with treatment-resistant depression: a systematic review. Lan, XJ., Yang, XH., Qin, ZJ., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39761754/

Efficacy study of intermittent theta burst stimulation(iTBS) in ... The current study suggests that two days of active iTBS to the DLPFC region can rapidly, safely, and effectively improve depressive symptoms in adolescents ...

2. nature.com nature.com/articles/s41380-024-02630-5

Theta burst stimulation for depression: a systematic review ... Theta burst stimulation (TBS) presents as a more efficient and potentially more effective therapeutic modality than conventional repetitive transcranial ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12243985/

Depression and anxiety outcomes of adults undergoing ... Depression and anxiety outcomes of adults undergoing intermittent theta burst stimulation (iTBS) treatment for major depressive disorder: A naturalistic study.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006322325013563

Efficacy and Safety of Accelerated Intermittent Theta-burst ... However, existing randomized controlled trials assessing the efficacy of rTMS in adolescents have yielded inconsistent results, with the largest ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT07033780

NCT07033780 | Theta-Burst Stimulation to Treat Depression This trial will compare the effects of the compressed iTBS (iTBS-c) protocol, which is commonly used to treat depression, and the spaced iTBS ( ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10423820/

Efficacy and safety of intermittent theta burst stimulation ... The antidepressant effects and safety of iTBS and HF-rTMS appeared to be similar for patients with TRD, although additional RCTs with rigorous ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8617062/

A Systematic Review of the Safety and Tolerability of Theta ... In 2018 the FDA cleared intermittent theta burst stimulation (iTBS) delivered to the left dorsolateral prefrontal cortex for the treatment of major ...