Effect of Bupropion on Seizure Threshold in Depressed Patients

MDD Clinical Trial

Official title:

Effect of Bupropion on Seizure Threshold in Depressed Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03126682
• Other study ID #: Pro00078738
• Status: Completed
• Phase: Phase 4
• Start date: August 25, 2017
• Est. completion date: May 31, 2018

Study information

• Verified date: June 2019
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to examine the effect of bupropion on seizure threshold and duration in depressed patients receiving right unilateral ultra-brief electroconvulsive therapy (ECT). The investigators plan to recruit 10 patients into the study, administer sustained release (SR) bupropion 4 hours prior to receiving ECT. The investigators plan to compare the seizure threshold and seizure durations between ECT sessions with and without bupropion administration. The study's implication is to examine how ECT can be optimized by rational combination with medications that lower seizure threshold.

Description:

Background and significance Depression is the leading cause of disability in individuals aged 15-44, resulting in 400 million disability days in a year (1). The total economic burden of the disease is estimated to be composed of $26.1 billion in direct medical costs, $5.4 billion in suicide-related mortality costs, and $51.5 billion in indirect workplace cost (1). Electroconvulsive therapy (ECT) is the gold-standard treatment for major depressive disorder (MDD) that is severe (2-5). The standard method of ECT used in the US now is right unilateral ultra-brief study. RUL ECT uses a pulse width of In addition, some studies show a reduction in efficacy with ultra-brief as compared to brief ECT with the former requiring higher number of ECTs to achieve remission in depression symptoms (8). There represents a need for increasing the efficacy for RUL ultra brief ECT given its favorable cognitive-side effect profile. Combining RUL ultra brief ECT with appropriate psychopharmacological agents to alter seizure profile is a feasible way of optimizing the efficacy.

Design and Procedures The study is designed to evaluate the effect of bupropion on seizure threshold in patients with major depressive disorder (MDD) referred for RUL ultra brief ECT. The study is powered to determine changes in seizure duration and seizure threshold by enrolling 10 subjects. The investigators plan to screen 20 subjects to have 10 participants. Potential participants will be discussed with the ECT team to which the patient would have been referred. Once a potential participant has been identified, a study team person will discuss the study and desire for participation in person with that individual during the ECT consult session which is needed prior to scheduling of the ECT session. If participants are found to be eligible they will be invited to participate in the study and the study will be initiated in conjunction with their first ECT session. Participants will go through the informed consent procedure. After providing informed consent participants will undergo a clinical assessment to confirm the inclusion/exclusion criteria.

Patients will receive ECT treatment as usual, but for this study if they choose to participate they will be randomized to receive bupropion (sustained release preparation 300 mg) (Wellbutrin ®), to be taken by mouth, in the morning (4 hours prior to ECT) on the day of ECT session 1 or session 2. There will be a one-time administration of bupropion at this dose with no discontinuation of medications that patient is already on. There will also be no washout period before bupropion administration or ECT.

The study is powered to determine changes in seizure duration and seizure threshold by enrolling 10 subjects (5 subjects will receive bupropion prior to ECT session 1 and 5 will receive it prior to ECT session 2). Counterbalanced randomization will be used to assign subject drug administration to ECT session 1 or 2 with inter-individual cross-over. The PI (Steven T Szabo Jr MD PhD) and coordinator (Gopalkumar Rakesh) would be blind to randomization details. Computer generated randomization would be done by Richard Weiner MD PhD - the director of the ECT program.

ECT administration The clinical procedure of ultra brief RUL ECT in these subjects will not be deviated from the usual procedure that is described below. ECT treatments will be provided three times a week, with standard right unilateral electrode placement with a MECTA spectrum device (MECTA Corporation, Portland, Ore.) with a pulse width Clinical assessments The Montgomery-Asberg Depression Rating Scale (MADRS) is an assessment tool for depression symptom severity and will be carried out at baseline at every ECT visit. This is usual practice that the ECT clinician employs prior to the clinical administration of ECT. The investigators will also measure time to orientation recovery post ECT after the first and second ECT treatments.

Blood Collection During ECT sessions 1 and 2, just prior to administration of right unilateral (RUL) ECT, patients will be placed with a venous catheter and the investigators will acquire from consenting study patients a serum sample to be used to ascertain serum bupropion level.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: May 31, 2018
• Est. primary completion date: May 31, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Male and female subjects, age >18.

2. Meeting diagnostic criteria for major depressive disorder or bipolar disorder per DSM5.

3. Referred for ultra brief RUL ECT.

4. Right motor dominant.

5. Competent to provide informed consent.

6. Able to read or comprehend English.

7. H/O treatment with bupropion.

8. Concomitant treatment with benzodiazepines, dosing of which has remained stable for a week prior to study ECT session.

Exclusion Criteria:

1. Lifetime history of schizophrenia, schizoaffective disorder, mental retardation, seizure disorder.

2. Current alcohol abuse or dependence within past 6 months.

3. Current substance abuse or dependence within past 6 months.

4. Recently received ECT within preceding 3-6 months.

5. Currently on any formulation of bupropion.

6. Currently on any anticonvulsants or clozapine.

Related Conditions & MeSH terms

• MDD
• Seizures

Intervention

Drug:
• Wellbutrin SR 300Mg Extended-Release Tablet
Wellbutrin SR 300Mg Extended-Release Tablet

Locations

Country	Name	City	State
United States	Duke University Medical Center	Durham	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Duke University

Country where clinical trial is conducted

United States, 

References & Publications (8)

Beckford-Ball J. An overview of the new NICE guidelines on bipolar disorder. Nurs Times. 2006 Aug 22-28;102(34):23-4. — View Citation

Fountoulakis KN, Vieta E, Sanchez-Moreno J, Kaprinis SG, Goikolea JM, Kaprinis GS. Treatment guidelines for bipolar disorder: a critical review. J Affect Disord. 2005 May;86(1):1-10. Review. — View Citation

Frances AJ, Kahn DA, Carpenter D, Docherty JP, Donovan SL. The Expert Consensus Guidelines for treating depression in bipolar disorder. J Clin Psychiatry. 1998;59 Suppl 4:73-9. — View Citation

Greenberg PE, Fournier AA, Sisitsky T, Pike CT, Kessler RC. The economic burden of adults with major depressive disorder in the United States (2005 and 2010). J Clin Psychiatry. 2015 Feb;76(2):155-62. doi: 10.4088/JCP.14m09298. — View Citation

Lisanby SH, Devanand DP, Nobler MS, Prudic J, Mullen L, Sackeim HA. Exceptionally high seizure threshold: ECT device limitations. Convuls Ther. 1996 Sep;12(3):156-64. — View Citation

Sackeim HA, Devanand DP, Prudic J. Stimulus intensity, seizure threshold, and seizure duration: impact on the efficacy and safety of electroconvulsive therapy. Psychiatr Clin North Am. 1991 Dec;14(4):803-43. Review. — View Citation

Tor PC, Bautovich A, Wang MJ, Martin D, Harvey SB, Loo C. A Systematic Review and Meta-Analysis of Brief Versus Ultrabrief Right Unilateral Electroconvulsive Therapy for Depression. J Clin Psychiatry. 2015 Sep;76(9):e1092-8. Review. — View Citation

Yatham LN, Kennedy SH, Parikh SV, Schaffer A, Beaulieu S, Alda M, O'Donovan C, Macqueen G, McIntyre RS, Sharma V, Ravindran A, Young LT, Milev R, Bond DJ, Frey BN, Goldstein BI, Lafer B, Birmaher B, Ha K, Nolen WA, Berk M. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013. Bipolar Disord. 2013 Feb;15(1):1-44. doi: 10.1111/bdi.12025. Epub 2012 Dec 12. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Seizure Threshold	Charge in Millicoulombs at which subject gets a seizure with ECT. First measurement on day 1 of electroconvulsive treatment (ECT) and second measurement on day 2 of electroconvulsive therapy (ECT), separated by 1 day interval. This outcome measure was not measured at baseline.	Measured at day 1 and day 2
Primary	Change in Seizure Duration	Duration of seizures with ECT. First measurement on day 1 of electroconvulsive treatment (ECT) and second measurement on day 2 of electroconvulsive therapy (ECT), separated by 1 day interval. This outcome measure was not measured at baseline.	Measured at day 1 and day 2
Secondary	Change in MADRS Score	Scoring of depressive symptoms on the Montgomery Asberg Depression Rating Scale, maximum 60 , minimum 0. Higher scores mean worse outcome. First measurement on day 1 of electroconvulsive treatment (ECT) and second measurement on day 2 of electroconvulsive therapy (ECT), separated by 1 day interval. This outcome measure was not measured at baseline.	Scored on day 1 and day 2 after ECT session