Ultrabrief Right Unilateral Electroconvulsive Therapy for Major Depression

(RAFT-ECT Trial)

Recruiting at 6 trial locations

Overseen By Mark George

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: The George Institute

Must not be taking: Benzodiazepines

Disqualifiers: Schizophrenia, Bipolar, Substance use, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 12

154 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two forms of electroconvulsive therapy (ECT) for treating severe depression, with a focus on reducing memory-related side effects. It tests Frontoparietal Ultrabrief Right Unilateral (UBRUL-FP) ECT, which may be more effective and cause fewer cognitive issues than the traditional Temporoparietal Ultrabrief Right Unilateral (UBRUL-TP) ECT. Participants will undergo ECT treatments and follow-ups to determine which method works better with fewer side effects. Ideal candidates are those diagnosed with a major depressive episode who require ECT and can manage medication adjustments as advised by their psychiatrist. As an unphased trial, this study offers patients the chance to contribute to innovative research that could enhance ECT treatments for severe depression.

Will I have to stop taking my current medications?

The trial requires participants to stop taking certain prohibited medications and restrict benzodiazepine dosage, as determined by their own treating psychiatrist. This is known as a washout period (time without taking certain medications).

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

Research has shown that ultrabrief right unilateral electroconvulsive therapy (ECT) could be a promising treatment for severe depression. Studies comparing electrode placement methods suggest that the Frontoparietal method might cause fewer memory problems than the traditional Temporoparietal method.

The Temporoparietal method, well-known and successful, can sometimes lead to memory issues. The newer Frontoparietal method aims to reduce these side effects while maintaining effectiveness.

In summary, both ECT methods are generally safe, but the Frontoparietal approach may better reduce memory problems. Prospective trial participants should consider these potential benefits and risks. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about ultrabrief right unilateral electroconvulsive therapy (UBRUL-ECT) for major depression because it aims to deliver effective results in a much shorter time frame compared to standard ECT, which often requires longer sessions. This treatment is unique due to its ultrabrief pulse width, which potentially reduces side effects like memory loss, a common concern with traditional ECT. Additionally, the study is exploring two different electrode placements—frontoparietal and temporoparietal—to determine which might optimize benefits and minimize side effects, making it a promising alternative to current treatments.

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

Research has shown that electroconvulsive therapy (ECT) is highly effective for treating severe depression. In this trial, participants will receive one of two methods of ultrabrief right unilateral ECT. The Frontoparietal ECT Group will have electrodes placed on the front and side of the head. Studies have found that this newer method can provide good results while causing fewer memory problems compared to the traditional method. The Temporoparietal ECT Group will have electrodes placed on the side and top of the head, which is also effective but tends to cause more memory-related side effects. Both methods aim to manage severe depression, but the newer approach may be gentler on memory. ^{1 4 5 6 7}

Who Is on the Research Team?

Colleen Loo

Principal Investigator

University of New South Wales

Anthony Rodgers

Principal Investigator

The George Institute

Are You a Good Fit for This Trial?

The RAFT ECT Study is for adults with severe depression who score at least 17 on the HRSD-17 scale, can speak English well enough for testing, and are able to follow study procedures. They must be considered suitable for ECT by their psychiatrist and have a cognitive assessment score of at least 23. Pregnant or breastfeeding women, recent ECT recipients, prisoners, those unable to make medical decisions, or individuals with certain mental health conditions or unstable medical issues cannot participate.

Inclusion Criteria

I can stop taking certain medications as advised by my psychiatrist.

Sufficient proficiency in spoken English to ensure validity of neuropsychological testing (e.g., worked or studied in an English-speaking context or equivalent)

HRSD-17 score ≥ 17 at Screening

Exclusion Criteria

Serious or unstable medical condition, as determined by study physician evaluation and medical history

I am not a prisoner and can make my own medical decisions.

I have a brain condition or injury that significantly affects my thinking, as confirmed by a doctor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Randomized Acute Treatment

Participants receive randomised acute ECT under blinded conditions, typically around 4 weeks

4 weeks

12 ECT sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Frontoparietal Ultrabrief Right Unilateral (UBRUL-FP) electroconvulsive therapy
• Temporoparietal Ultrabrief Right Unilateral (UBRUL-TP) electroconvulsive therapy

Trial Overview This trial compares two types of electroconvulsive therapy (ECT) for major depression: Temporoparietal Ultrabrief Right Unilateral (UBRUL-TP) and Frontoparietal UBRUL (UBRUL-FP). Participants will receive random treatments over about four weeks under blinded conditions followed by a six-month observation period. The goal is to see if Frontoparietal placement reduces memory side effects compared to the conventional Temporoparietal approach.

How Is the Trial Designed?

Group I: Frontoparietal ECT Group Experimental Treatment 1 Intervention

Participants will receive ultrabrief right unilateral ECT with a frontoparietal placement of ECT electrodes.

Group II: Temporoparietal ECT Group Active Control 1 Intervention

Participants will receive ultrabrief right unilateral ECT with the conventional temporoparietal placement of ECT electrodes.

Frontoparietal Ultrabrief Right Unilateral (UBRUL-FP) electroconvulsive therapy is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Electroconvulsive Therapy for:

• Severe depression
• Bipolar disorder
• Catatonia

Approved in European Union as Electroconvulsive Therapy for:

• Severe depression
• Bipolar disorder
• Catatonia
• Schizophrenia

Approved in Canada as Electroconvulsive Therapy for:

• Severe depression
• Bipolar disorder
• Catatonia

Who Is Running the Clinical Trial?

The George Institute

Lead Sponsor

Trials

84

Recruited

275,000+

Ramsay Clinic Lakeside, Australia

Collaborator

Trials

1

Recruited

150+

Ramsay Clinic Northside, Australia

Collaborator

Trials

1

Recruited

150+

Emory University

Collaborator

Trials

1,735

Recruited

2,605,000+

National Health and Medical Research Council, Australia

Collaborator

Trials

167

Recruited

473,000+

Ramsay Clinic Albert Road, Australia

Collaborator

Trials

1

Recruited

150+

The University of New South Wales

Collaborator

Trials

122

Recruited

229,000+

Gold Coast Hospital and Health Service

Collaborator

Trials

13

Recruited

10,600+

Augusta University

Collaborator

Trials

219

Recruited

85,900+

Medical University of South Carolina

Collaborator

Trials

994

Recruited

7,408,000+

Published Research Related to This Trial

In a case study of a patient with catatonic schizophrenia, switching from bilateral brief pulse (BL-BP) electroconvulsive therapy (ECT) to right unilateral ultrabrief pulse (RUL-UBP) ECT successfully induced therapeutic seizures when the former failed, leading to complete remission.

This suggests that RUL-UBP ECT may be a valuable alternative for patients who have a high seizure threshold and struggle to achieve adequate seizure induction with conventional ECT methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful switch from bilateral brief pulse to right unilateral ultrabrief pulse electroconvulsive therapy after failure to induce seizures. Kawashima, H., Kobayashi, Y., Suwa, T., et al.[2020]

In a study of 75 depressed patients receiving ultrabrief right unilateral ECT, 61% showed a positive response and 36% achieved remission, indicating its efficacy in treating depression.

Predictors of response included having a longer duration of the current depressive episode, fewer previous antidepressant treatments, and not being on concurrent antidepressants, while psychotic features and baseline severity were linked to remission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of response to ultrabrief right unilateral electroconvulsive therapy. Loo, CK., Mahon, M., Katalinic, N., et al.[2011]

In a single patient study comparing frontoparietal and temporoparietal electrode placements for right unilateral electroconvulsive therapy (ECT), the frontoparietal montage resulted in a significantly shorter time-to-reorientation (28.3 minutes) compared to the temporoparietal montage (50.0 minutes), indicating potentially less memory impairment.

Both montages produced similar seizure duration and expression, while computer modeling suggested that the frontoparietal montage stimulated less of the hippocampus and right inferior frontal cortex, which may contribute to its reduced memory side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Revisiting frontoparietal montage in electroconvulsive therapy: clinical observations and computer modeling: a future treatment option for unilateral electroconvulsive therapy. Loo, CK., Bai, S., Martin, D., et al.[2015]

In a study of 23 elderly patients receiving electroconvulsive therapy (ECT), Right Unilateral Ultrabrief (RUL(UB)) ECT was found to be effective in treating their conditions, similar to Bitemporal (BT) ECT.

Patients who underwent RUL(UB) ECT experienced significantly less post-treatment confusion compared to those who received BT ECT, suggesting a safety advantage for the RUL(UB) approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison between Right Unilateral Ultrabrief electroconvulsive therapy and bilateral electroconvulsive therapy in the elderly: a pilot naturalistic observational study. Narchal, S., Harris, AW., Allen, B.[2019]

In a study of 87 inpatients who received either right unilateral brief pulse (BP) or ultrabrief pulse (UBP) electroconvulsive therapy (ECT), both groups showed similar relapse rates after three and six months, indicating comparable long-term efficacy of both ECT methods.

Cognitive assessments revealed no significant advantages for UBP over BP ECT, except for a slight benefit in autobiographical memory for the BP group at three months, suggesting that UBP does not provide cognitive benefits over traditional BP ECT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relapse and long-term cognitive performance after brief pulse or ultrabrief pulse right unilateral electroconvulsive therapy: A multicenter naturalistic follow up. Verwijk, E., Spaans, HP., Comijs, HC., et al.[2018]

An 80-year-old male with AFP-producing lung cancer showed a favorable response to single oral administrations of UFT (Tegafur) after surgery for brain metastasis, with significant tumor shrinkage observed at 15 weeks.

UFT treatment resulted in no side effects, allowing for outpatient management and improving the patient's quality of life while effectively reducing tumor size and AFP levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effective treatment of AFP-producing lung cancer with UFT]. Hirota, F., Hosaka, K., Funahashi, K., et al.[2013]

In a study of 1383 patients receiving their first course of right unilateral brief pulse (RUL-BP) electroconvulsive therapy (ECT), over 60% continued with RUL-BP parameters throughout their treatment, indicating its effectiveness and acceptance as a primary approach.

Only 37.5% of patients transitioned to bilateral ECT, with younger patients and those with bipolar disorder being more likely to switch, suggesting that RUL-BP may be a preferred option for many patients due to its reduced cognitive side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duration of Treatment in Electroconvulsive Therapy Among Patients Beginning With Acute Course Right Unilateral Brief Pulse Stimuli. Luccarelli, J., McCoy, TH., Shannon, AP., et al.[2023]

In a study of 56 patients with depression, those receiving high-dose ultrabrief right unilateral (UB-RUL) electroconvulsive therapy (ECT) required significantly more treatments to achieve remission compared to those receiving bilateral (BL) ECT (9.4 vs 7.7 treatments).

Nearly half (46%) of the patients on UB-RUL ECT experienced insufficient effectiveness or seizure induction, leading to a switch to BL ECT, which suggests that while UB-RUL may have fewer memory side effects, it may be less efficient in treating depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relative ineffectiveness of ultrabrief right unilateral versus bilateral electroconvulsive therapy in depression. McCormick, LM., Brumm, MC., Benede, AK., et al.[2009]

In a study of 32 gastric cancer patients undergoing the ECU-E regimen, 8 patients were evaluated for pharmacokinetics of tegafur, revealing that absorption rates significantly affected plasma levels, with rapid absorbers showing much higher concentrations than slow absorbers.

Preliminary results indicated that higher plasma concentrations of tegafur correlated with better treatment responses, suggesting that tegafur levels may be important for its effectiveness in treating gastric cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Pharmacokinetics of Tegafur Administered with Epirubicin and Cisplatin in Patients with Advanced Gastric Cancer. Kang, JH., Kim, YL., Cho, HK., et al.[2015]

UFT combined with leucovorin shows equivalent antitumor efficacy to intravenous 5-FU plus leucovorin in treating advanced colorectal cancer, but with reduced toxicity, making it a safer option.

UFT may offer a more convenient treatment method with fewer complications, and it is also being explored for effectiveness in breast cancer treatment, pending FDA approval for its use in colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

UFT in the treatment of colorectal and breast cancer. Sun, W., Haller, D.[2013]

Left unilateral (LUL) electrode placement for electroconvulsive therapy (ECT) is as effective as right unilateral (RUL) and bilateral (BL) placements in treating depression and psychosis, based on a review of 52 studies.

Patients receiving LUL ECT experience more verbal memory impairment than those with RUL ECT but less than those with BL ECT, while showing the least visual and nonverbal memory impairment compared to both RUL and BL ECT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of left unilateral electroconvulsive therapy. Kellner, CH., Farber, KG., Chen, XR., et al.[2018]

A patient with advanced stage IVb gastric cancer experienced an 89% reduction in tumor size after 18 months of low-dose chemotherapy combining tegafur and cisplatin, indicating significant anti-tumor efficacy.

The treatment was well-tolerated with no adverse reactions reported, allowing the patient to maintain a good quality of life while receiving therapy on an outpatient basis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Case of stage IVb gastric cancer in which favorable anti-tumor effect and good QOL were observed due to UFTP therapy after low-dose CDDP-tegafur therapy]. Takai, S., Taki, S., Fujino, R., et al.[2013]

A 67-year-old man with gallbladder cancer experienced lymph node recurrence 10 months after surgery, which was successfully treated with UFT chemotherapy at a dosage of 400 mg.

After one month of UFT treatment, follow-up CT scans showed no detectable lymph node recurrence, suggesting that UFT may be an effective chemotherapy option for managing lymph node recurrence in gallbladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A case of para-aortic lymph node recurrence of gallbladder cancer completely responding to single drug (UFT) chemotherapy]. Matsuyama, S., Takei, M., Kido, S., et al.[2013]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38968425/

A Randomized Controlled Trial of Ultrabrief Right ... A randomized controlled trial of ultrabrief right unilateral ECT with frontoparietal versus temporoparietal electrode placement for severe depression.

2. anzctr.org.au anzctr.org.au/Trial/Registration/TrialReview.aspx?id=20546&isClinicalTrial=True

ANZCTR - Registration The Randomised Controlled Trial of Frontoparietal and Temporoparietal Electroconvulsive Therapy (ECT) for Severe Depression: The RAFT ECT Study

3. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X21002461

Effects of modifying the electrode placement and pulse ... This study explored use of the frontoparietal (FP) placement for reducing retrograde memory side effects with ECT. We hypothesised that superior retrograde ...

4. augusta.elsevierpure.com augusta.elsevierpure.com/en/publications/a-randomized-controlled-trial-of-ultrabrief-right-unilateral-ect-

A Randomized Controlled Trial of Ultrabrief Right ... A Randomized Controlled Trial of Ultrabrief Right Unilateral ECT With Frontoparietal Versus Temporoparietal Electrode Placement for Severe ...

5. adaa.trialstoday.org adaa.trialstoday.org/trial/NCT05402657

Anxiety & Depression Association of America Preliminary data suggest that Frontoparietal UBRUL has good efficacy and less cognitive side effects than UBRUL given using the conventional ...

6. withpower.com withpower.com/trial/phase-major-depressive-episode-6-2022-ab3dc

Ultrabrief Right Unilateral Electroconvulsive Therapy for ... Trial Overview This trial compares two types of electroconvulsive therapy (ECT) for major depression: Temporoparietal Ultrabrief Right Unilateral (UBRUL-TP) and ...

7. journals.lww.com journals.lww.com/ectjournal/fulltext/2007/03000/a_trial_of_the_effectiveness_and_safety_of_4_forms.24.aspx

A Trial of the Effectiveness and Safety of 4 forms of ECT This study aimed to investigate the relative effectiveness and cognitive side effects of ECT given in four different forms, varying in electrode placement and ...