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

30 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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 IV Citalopram + TMS safe for humans?

The safety of intermittent theta burst stimulation (iTBS), a form of transcranial magnetic stimulation (TMS), has been evaluated in several studies for depression, showing it to be generally safe and well-tolerated in humans. No adverse events were observed in a study on bipolar depression, and it has a similar safety profile to other TMS methods for treatment-resistant depression. ^{1 2 3 4 5}

How is the treatment of IV Citalopram + TMS for depression different from other treatments?

This treatment combines IV Citalopram, a medication for depression, with Intermittent Theta Burst Stimulation (iTBS), a newer form of brain stimulation that is faster and requires less intensity than traditional methods. This combination may offer a unique approach by potentially enhancing the effects of both components for those with treatment-resistant depression. ^{1 2 4 6 7}

What data supports the effectiveness of the drug citalopram for depression?

Research shows that citalopram, when used as an additional treatment for patients who don't fully respond to other depression medications, can significantly improve symptoms compared to a placebo. A meta-analysis also found that citalopram is more effective than a placebo in reducing symptoms of major depressive disorder. ^{8 9 10 11 12}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

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2. United States pubmed.ncbi.nlm.nih.gov

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Citalopram for major depressive disorder in adults: a systematic review and meta-analysis of published placebo-controlled trials. [2021]

6. Ireland 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. [2023]

7. England 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. [2022]

8. France pubmed.ncbi.nlm.nih.gov

Twice-daily neuronavigated intermittent theta burst stimulation for bipolar depression: A Randomized Sham-Controlled Pilot Study. [2020]

9. Switzerland 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. [2023]

10. Ireland pubmed.ncbi.nlm.nih.gov

Prolonged intermittent theta burst stimulation in the treatment of major depressive disorder: a case series. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Impact of prior treatment on remission with intermittent theta burst versus high-frequency repetitive transcranial magnetic stimulation in treatment resistant depression. [2020]

12. England pubmed.ncbi.nlm.nih.gov

The antidepressant effect of intermittent theta burst stimulation (iTBS): study protocol for a randomized double-blind sham-controlled trial. [2023]