Low Amplitude Pulse Seizure Therapy for Suicidal Thoughts

(LAP-ST vs ECT Trial)

Overseen By Janelle M Kassien, LMSW

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Michigan State University

Disqualifiers: Pregnancy, Neurological disorder, Dementia, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This protocol proposes an initial randomized clinical trial that includes all patients with suicidal ideation (SI) at baseline, and with SI as the primary outcome measure to examine whether Right Unilateral Low-Amplitude Pulse - Seizure Therapy (RUL LAP-ST) treatment has more magnitude and rate of remission of SI as conventional pulse amplitude Right Unilateral Electroconvulsive Therapy (RUL ECT) (based on our prior secondary analysis). Our central hypothesis is that RUL LAP-ST has significantly less cognitive/memory side effects (no memory side effects were noted in our prior studies for 500mA and 600mA) and thus is more favorable in terms of side effects compared to RUL conventional pulse amplitude ECT, while maintaining better anti-suicidal effect.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify that you must stop taking your current medications, but it mentions there should be no anticipated need to change psychotropic medications (medications affecting mood, perception, or behavior) during the study, except in urgent situations.

What data supports the effectiveness of Low Amplitude Pulse Seizure Therapy for reducing suicidal thoughts?

Research shows that Low Amplitude Pulse Seizure Therapy (LAP-ST) can reduce suicidal thoughts more quickly and effectively than standard electroconvulsive therapy (ECT), with all patients experiencing remission of suicidality by the fourth session. ^{1 2 3 4 5}

Is Low Amplitude Pulse Seizure Therapy safe for humans?

Research on Right Unilateral Ultra-Brief Pulse Electroconvulsive Therapy (RUL-UBP ECT), a related treatment, suggests it is generally safe and aims to minimize cognitive side effects while being effective. However, further studies are needed to determine the optimal dosing for safety. ^{6 7 8 9 10}

How does Low Amplitude Pulse Seizure Therapy differ from other treatments for suicidal thoughts?

Low Amplitude Pulse Seizure Therapy (LAP-ST) is unique because it uses a lower electrical pulse amplitude compared to standard electroconvulsive therapy (ECT), which may reduce cognitive side effects while still effectively reducing suicidal thoughts more quickly. This makes it potentially safer and faster-acting than traditional ECT methods. ^{1 3 4 5 11}

Research Team

Nagy A Youssef, MD, PhD

Principal Investigator

Pine Rest Christian Mental Health Services & Michigan State University

Eligibility Criteria

This trial is for patients with suicidal thoughts or mood disorders like major depressive disorder, bipolar disorder, psychosis, and schizoaffective disorder. Participants must be experiencing these conditions at the start of the study.

Inclusion Criteria

I have been diagnosed with a major depressive episode as per DSM-5.

Use of effective method of birth control for women of child-bearing capacity

I am between 18 and 90 years old.

Exclusion Criteria

History of neurological disorder if deemed by the treating ECT physician or PI to pose a significant risk with ECT, or if there is any metal in the head or history of known structural brain lesion or skull defect that is deemed to affect cognition or safe ECT treatment

I do not have a serious condition that could worsen with ECT or affect my thinking.

I am not pregnant, planning to become pregnant, or breastfeeding during the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either RUL LAP-ST or RUL ECT to assess remission of suicidal ideation and cognitive side effects

4 weeks

Multiple sessions per week

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Low Amplitude Pulse Seizure Therapy
• Standard Ultra-Brief Right Unilateral Electroconvulsive Therapy

Trial Overview The trial is testing a new treatment called Right Unilateral Low-Amplitude Pulse - Seizure Therapy (RUL LAP-ST) against standard Right Unilateral Electroconvulsive Therapy (RUL ECT). The focus is on which treatment better reduces suicidal thoughts without causing memory issues.

Participant Groups

Group I: RUL LAP-ST (Low-Amplitude Pulse Seizure Therapy - Right Unilateral) Experimental Treatment 1 Intervention

Low Amplitude Pulse Seizure Therapy RUL ECT at 600mA (or 700mA)

Group II: RUL ECT (Electroconvulsive Therapy) Active Control 1 Intervention

RUL Conventional pulse amplitude Electroconvulsive Therapy (ECT)

Low Amplitude Pulse Seizure Therapy is already approved in United States, European Union, Switzerland for the following indications:

Approved in United States as Electroconvulsive Therapy (ECT) for:

• Major depressive disorder
• Catatonia
• Acute schizophrenic exacerbations
• Bipolar disorder
• Mania

Approved in European Union as Electroconvulsive Therapy (ECT) for:

• Severe depressive episodes
• Catatonia
• Treatment-resistant schizophrenic disorders

Approved in Switzerland as Electroconvulsive Therapy (ECT) for:

• Severe depressive episodes
• Catatonia
• Treatment-resistant schizophrenic disorders

Who Is Running the Clinical Trial?

Michigan State University

Lead Sponsor

Trials

202

Recruited

687,000+

Pine Rest Christian Mental Health Services

Collaborator

Trials

6

Recruited

520+

Findings from Research

In two cases of patients experiencing prolonged seizures during electroconvulsive therapy (ECT), treatment was safely continued using right unilateral ECT at a higher suprathreshold dose, resulting in no further seizures and significant clinical improvement.

The use of ultrabrief right unilateral ECT appears to reduce cognitive side effects while allowing for effective treatment, suggesting that prolonged seizures should not automatically halt ECT therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selecting right unilateral placement to facilitate continuation of electroconvulsive therapy following prolonged seizures. Goh, SE., Tor, PC.[2021]

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]

Low Amplitude Seizure Therapy (LAP-ST) demonstrated a greater reduction in suicidal ideation compared to standard Right Unilateral Electroconvulsive Therapy (RUL ECT), with an average improvement score of 5.1 for LAP-ST versus 3.0 for RUL ECT among 7 patients with major depressive episodes.

All patients receiving LAP-ST experienced remission of suicidality by the fourth session, indicating that LAP-ST not only has a larger effect size but also a faster speed of remission compared to RUL ECT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnitude of Reduction and Speed of Remission of Suicidality for Low Amplitude Seizure Therapy (LAP-ST) Compared to Standard Right Unilateral Electroconvulsive Therapy: A Pilot Double-Blinded Randomized Clinical Trial. Youssef, NA., Ravilla, D., Patel, C., et al.[2023]

Low Pulse Amplitude Seizure Therapy (LAP-ST) was found to be feasible for inducing seizures in all 22 patients with treatment-resistant mood or psychotic disorders, suggesting it can be safely implemented in clinical settings.

Preliminary results indicate that LAP-ST may reduce cognitive side effects compared to standard ECT while maintaining similar efficacy for treating depressive and psychotic symptoms, although further research with larger sample sizes is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility, safety, and preliminary efficacy of Low Amplitude Seizure Therapy (LAP-ST): A proof of concept clinical trial in man. Youssef, NA., Sidhom, E.[2022]

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 1793 patients receiving their first course of ECT, 65.6% were treated exclusively with right unilateral ultrabrief pulse (RUL-UBP) ECT, indicating its widespread use and potential as a primary treatment method.

The mean dose of RUL-UBP ECT increased significantly from 7.6 times the seizure threshold at the second treatment to 14.3 times by the twelfth treatment, suggesting that while RUL-UBP is effective, adjustments in dosing may be necessary as treatment progresses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rate of continuing acute course treatment using right unilateral ultrabrief pulse electroconvulsive therapy at a large academic medical center. Luccarelli, J., McCoy, TH., Shannon, AP., et al.[2022]

Recent studies suggest that monotherapy, particularly with valproate, can provide equal or better seizure control compared to polypharmacy in epilepsy management, reducing the risk of adverse reactions and improving patient compliance.

Valproate is shown to be at least as effective as other common anticonvulsants like phenytoin and carbamazepine for treating both generalized and partial seizures, indicating it is a strong option for monotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Valproate monotherapy in the management of generalized and partial seizures. Chadwick, DW.[2019]

In a small study of three adults with ultrarefractory epilepsy, the dopaminergic agent Madopar showed promise by reducing or even eliminating tonic-clonic seizures in two patients after they had failed multiple antiepileptic drugs.

However, Madopar may worsen absence seizures in some cases, indicating that while it could be a potential treatment option, further research through randomized controlled trials is necessary to confirm its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive Madopar for ultrarefractory epilepsy? Preliminary observations. Hodoba, D., Santic, AM., Schmidt, D.[2014]

In a study of 17 children with nocturnal or early-morning seizures, adjusting their evening doses of antiepileptic drugs resulted in a significant response, with 64.7% achieving seizure freedom and 88.2% experiencing at least a 50% reduction in seizures after a mean follow-up of 5.3 months.

The approach was safe, as none of the children experienced worsening seizures, and only two reported mild side effects, indicating that differential dosing can be an effective and well-tolerated strategy for managing certain types of epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Higher evening antiepileptic drug dose for nocturnal and early-morning seizures. Guilhoto, LM., Loddenkemper, T., Vendrame, M., et al.[2018]

Antiepileptic drugs (AEDs) effectively suppress seizures but do not change the underlying disease process and can have side effects, including teratogenic risks, making their long-term use challenging.

For treating epilepsy, specific AEDs like oxcarbazepine, carbamazepine, and lamotrigine are recommended based on patient age and type of seizures, with treatment tailored to individual needs, especially for women of childbearing age.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating epilepsy across its different stages. Beghi, E.[2021]

In a study of 40 patients with major depression, those receiving suprathreshold right unilateral ultrabrief-pulse ECT at a lower frequency of 40 Hz showed significantly greater improvement in depression scores compared to those treated at 100 Hz after 9 sessions.

Both frequency groups did not show significant differences in verbal and working memory, suggesting that the lower frequency ECT may be more effective without increasing cognitive side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stimulus pulse-frequency-dependent efficacy and cognitive adverse effects of ultrabrief-pulse electroconvulsive therapy in patients with major depression. Roepke, S., Luborzewski, A., Schindler, F., et al.[2012]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Selecting right unilateral placement to facilitate continuation of electroconvulsive therapy following prolonged seizures. [2021]

2. 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]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Magnitude of Reduction and Speed of Remission of Suicidality for Low Amplitude Seizure Therapy (LAP-ST) Compared to Standard Right Unilateral Electroconvulsive Therapy: A Pilot Double-Blinded Randomized Clinical Trial. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Feasibility, safety, and preliminary efficacy of Low Amplitude Seizure Therapy (LAP-ST): A proof of concept clinical trial in man. [2022]

5. 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]

6. Germany pubmed.ncbi.nlm.nih.gov

Rate of continuing acute course treatment using right unilateral ultrabrief pulse electroconvulsive therapy at a large academic medical center. [2022]

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

Valproate monotherapy in the management of generalized and partial seizures. [2019]

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

Adjunctive Madopar for ultrarefractory epilepsy? Preliminary observations. [2014]

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

Higher evening antiepileptic drug dose for nocturnal and early-morning seizures. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Treating epilepsy across its different stages. [2021]

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

Stimulus pulse-frequency-dependent efficacy and cognitive adverse effects of ultrabrief-pulse electroconvulsive therapy in patients with major depression. [2012]