Bipolar Depression, Major Depression, Schizoaffective Disorder
Conditions
Brief summary
The purpose of the study is to see if galantamine HBr (Razadyne) is safe and can help treat problems with thinking and memory caused by electroconvulsive therapy (ECT).
Interventions
DRUGRazadyne
The starting dose of study medication is 4 mg twice a day
DRUGPlacebo
4 mg, 2 times a day
Sponsors
Ortho-McNeil Janssen Scientific Affairs, LLC
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Criteria to enter the study include males and females between the ages of 18-90 (females must be post menopausal) and a DSM-IV diagnosis of Major Depressive Disorder, Major Depressive Disorder with psychotic features, Bipolar Disorder, depressed type, or Schizoaffective Disorder, depressed type (19).
Exclusion criteria
* DSM-IV diagnoses of dementia and its subtypes * Substance use disorder (active use within the last 6 months) * Organic mental disorders; seizure disorder * Unstable physical disorder or physical disorder judged to significantly affect the central nervous system function * A heart rate of \<60 * A systolic blood pressure \< 90 * Heart block * Pre-existing sick-sinus * Chronic treatment with beta blockers * Any cardiac arrythmia * Hypotension * Coronary artery disease * Liver and renal function impairment * Urge incontinence, colitis Crohn's disease, GI motility disorders, asthma and COPD * Treatment with anti-cholinergic and cholinomimetic medications; and * Female patients who are pregnant. * Additionally, women subjects must be postmenopausal, surgically sterile, or using prescription oral contraceptives (e.g. estrogen-progestin combinations) , contraceptive implants (e.g. NorplantTM, DepoProveraTM ), or transdermally delivered contraceptives (Ortho EvraTM) before entry and throughout the study; and have a negative serum b-HCG pregnancy test at screening. Note: Abstinence and the use of double barrier contraceptive methods are not acceptable in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Side Effects | Participants were followed for the duration of hospital stay, an average of 3 weeks | This measure refers to the number of reported side effects experienced by participants during the study. The side effects were nausea, headache, dizziness, diarrhea, and vomiting. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cognitive Functioning | Participants were questioned at baseline and after their last electroconvulsive therapy treatment | This measure refers to participants' scores on the Delayed Memory Index (DMI) compared from baseline (before first ECT) to discharge (after last ECT). The score can range from 40 to 137. The higher the score, the better, in terms of cognitive functioning. |
| Baseline Depressive Symptoms | Participants were questioned at baseline | This measure refers to the Hamilton Rating Scale for Depression-17 scores (HAM-D-17) which can range from 0 to 50, with \<7 referring to mild-to-no depression, and \>23 referring to severe depression. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Patients with major depression, bipolar disorder (depressed type) or schizoaffective disorder (depressed type) received placebo (sugar pills) and treatment-as-usual electroconvulsive therapy. | 18 |
| Galantamine Patients with major depression, bipolar disorder (depressed type) or schizoaffective disorder (depressed type) received galantamine tablets 4 milligrams twice daily (increased every three days until a target of 8 milligrams twice daily) and treatment-as-usual electroconvulsive therapy. | 12 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Refused neuropsychological testing | 2 | 5 |
| Overall Study | Switched into a manic episode | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Galantamine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 3 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 9 Participants | 23 Participants |
| Clinical-Global Impressions - Severity (CGI-S) | 4.75 CGI-S Score STANDARD_DEVIATION 0.62 | 4.41 CGI-S Score STANDARD_DEVIATION 0.87 | 4.61 CGI-S Score STANDARD_DEVIATION 0.72 |
| Hamilton Depression Rating Scale 17 (HAM-D-17) | 27.33 HAM-D-17 Score STANDARD_DEVIATION 4.33 | 24.53 HAM-D-17 Score STANDARD_DEVIATION 4.33 | 26.21 HAM-D-17 Score STANDARD_DEVIATION 4.33 |
| Modified Mini Mental Status Exam (3MSE) | 91.72 3MSE Score STANDARD_DEVIATION 8.05 | 90.41 3MSE Score STANDARD_DEVIATION 5.48 | 91.20 3MSE Score STANDARD_DEVIATION 7.02 |
| Sex: Female, Male Female | 11 Participants | 6 Participants | 17 Participants |
| Sex: Female, Male Male | 7 Participants | 6 Participants | 13 Participants |
| Subjective Mood | 8.0 Subjective Mood Score STANDARD_DEVIATION 1.54 | 7.88 Subjective Mood Score STANDARD_DEVIATION 1.93 | 7.95 Subjective Mood Score STANDARD_DEVIATION 1.7 |
| Wechsler Abbreviated Scale of Intelligence (WASI) | 102.16 WASI Score STANDARD_DEVIATION 18.21 | 104.57 WASI Score STANDARD_DEVIATION 12.35 | 103.12 WASI Score STANDARD_DEVIATION 15.87 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 19 / 19 | 13 / 18 |
| serious Total, serious adverse events | 0 / 19 | 0 / 18 |
Outcome results
Primary
Number of Side Effects
This measure refers to the number of reported side effects experienced by participants during the study. The side effects were nausea, headache, dizziness, diarrhea, and vomiting.
Time frame: Participants were followed for the duration of hospital stay, an average of 3 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Side Effects | 19 Number of reported side effects |
| Galantamine | Number of Side Effects | 13 Number of reported side effects |
Secondary
Baseline Depressive Symptoms
This measure refers to the Hamilton Rating Scale for Depression-17 scores (HAM-D-17) which can range from 0 to 50, with \<7 referring to mild-to-no depression, and \>23 referring to severe depression.
Time frame: Participants were questioned at baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Baseline Depressive Symptoms | 24.53 Score on the HAM-D-17 | Standard Deviation 4.33 |
| Galantamine | Baseline Depressive Symptoms | 27.33 Score on the HAM-D-17 | Standard Deviation 4.33 |
Secondary
Cognitive Functioning
This measure refers to participants' scores on the Delayed Memory Index (DMI) compared from baseline (before first ECT) to discharge (after last ECT). The score can range from 40 to 137. The higher the score, the better, in terms of cognitive functioning.
Time frame: Participants were questioned at baseline and after their last electroconvulsive therapy treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Cognitive Functioning | Pre-ECT | 80.33 Score on the DMI | Standard Deviation 17.87 |
| Placebo | Cognitive Functioning | Post-ECT | 68.50 Score on the DMI | Standard Deviation 22.65 |
| Galantamine | Cognitive Functioning | Pre-ECT | 88.75 Score on the DMI | Standard Deviation 15.64 |
| Galantamine | Cognitive Functioning | Post-ECT | 88.17 Score on the DMI | Standard Deviation 19.84 |
Comparison: Independent t-test to assess differences between the placebo and galantamine groups in regard to pre- and post-ECT scores on the Delayed Memory Index (DMI).p-value: <0.05t-test, 1 sided