Ultrabrief Right Unilateral Electroconvulsive Therapy for Major Depression

(RAFT-ECT Trial)

Recruiting at 6 trial locations

Overseen By Adriana Hermida

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

Trial Summary

What is the purpose of this trial?

Severe depression is devastating for those affected and is often associated with significant risk of suicide. Electroconvulsive therapy (ECT) is a highly effective acute treatment for severe depression, but its use and acceptability are limited by cognitive side effects. Of these, retrograde memory loss is most concerning, and can be long-term. The introduction of ultrabrief right unilateral (UBRUL) ECT into clinical practice has been an important step in reducing the risk of memory impairment, but significant deficits still occur. A new form of UBRUL ECT which utilises a Frontoparietal electrode placement represents a further development. Preliminary data suggest that Frontoparietal UBRUL has good efficacy and less cognitive side effects than UBRUL given using the conventional Temporoparietal electrode placement. Designed as a pivotal trial, this protocol will be the first RCT comparing these two forms of ECT, producing the rigorous efficacy and safety data required to change clinical practice/policy. This is a multicentre, parallel group RCT with 1:1 allocation ratio between Frontoparietal (intervention) and Temporoparietal (comparator) forms of UBRUL ECT. Participation will involve receiving randomised acute ECT under blinded conditions during the randomised acute treatment period (typically around 4 weeks), then completion of a 24-week follow-up period which commences after the cessation of all acute ECT. The study protocol aims to provide 12 randomised acute ECT treatments, though the number of treatments (and hence the length of the randomised acute treatment period) can be adjusted by the participant's own treating/admitting psychiatrist according to their clinical judgement.

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).

What data supports the effectiveness of the treatment Ultrabrief Right Unilateral Electroconvulsive Therapy for Major Depression?

Research suggests that ultrabrief right unilateral electroconvulsive therapy (ECT) may have similar effectiveness to the more commonly used bilateral ECT, with the potential benefit of reducing short-term memory problems. However, more studies are needed to fully understand its long-term cognitive effects and overall efficiency. ^{1 2 3 4 5}

Is ultrabrief right unilateral electroconvulsive therapy safe for humans?

Recent studies show that ultrabrief right unilateral electroconvulsive therapy (ECT) has minimal cognitive side effects, making it a safer option compared to other ECT methods. ^{1 2 6 7 8}

What makes Ultrabrief Right Unilateral Electroconvulsive Therapy unique for treating major depression?

Ultrabrief Right Unilateral Electroconvulsive Therapy (ECT) is unique because it uses a very short pulse width and targets specific brain regions, potentially reducing side effects like memory loss compared to traditional ECT methods. This approach aims to maintain the effectiveness of ECT while minimizing cognitive side effects, making it a novel option for patients with major depression. ^{9 10 11 12 13}

Research Team

Colleen Loo

Principal Investigator

University of New South Wales

Anthony Rodgers

Principal Investigator

The George Institute

Eligibility Criteria

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)

I am 18 years old or older.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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 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 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]

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]

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]

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]

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]

References

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

Revisiting frontoparietal montage in electroconvulsive therapy: clinical observations and computer modeling: a future treatment option for unilateral electroconvulsive therapy. [2015]

2. Netherlands 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. [2018]

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

A systematic review of left unilateral electroconvulsive therapy. [2018]

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

Duration of Treatment in Electroconvulsive Therapy Among Patients Beginning With Acute Course Right Unilateral Brief Pulse Stimuli. [2023]

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

Relative ineffectiveness of ultrabrief right unilateral versus bilateral electroconvulsive therapy in depression. [2009]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Successful switch from bilateral brief pulse to right unilateral ultrabrief pulse electroconvulsive therapy after failure to induce seizures. [2020]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Predictors of response to ultrabrief right unilateral electroconvulsive therapy. [2011]

8. England 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. [2019]

9. Japan pubmed.ncbi.nlm.nih.gov

[Effective treatment of AFP-producing lung cancer with UFT]. [2013]

10. Japan 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]. [2013]

11. Korea (South) pubmed.ncbi.nlm.nih.gov

Clinical Pharmacokinetics of Tegafur Administered with Epirubicin and Cisplatin in Patients with Advanced Gastric Cancer. [2015]

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

UFT in the treatment of colorectal and breast cancer. [2013]

13. Japan pubmed.ncbi.nlm.nih.gov

[A case of para-aortic lymph node recurrence of gallbladder cancer completely responding to single drug (UFT) chemotherapy]. [2013]