Depression
Conditions
Keywords
Major depressive disorder, Rehabilitating, Elderly, Apathy
Brief summary
This study will evaluate the effectiveness of memantine in improving rehabilitation outcomes and preventing major depressive disorder in older adults who have been admitted to a rehabilitation hospital for a hip fracture or cardiopulmonary condition.
Detailed description
Depression is a serious medical illness that is often difficult to diagnose and treat. It occurs in people of all ages, but is often overlooked in older adults. Depression frequently co-occurs with other serious illnesses, and may be mistaken by both patients and health care givers as a normal consequence of the illness. However, these misconceptions toward depression contribute to the underdiagnosis and undertreatment of depressive disorders in older people. In turn, depression may hinder a patient's recovery from an illness. This study will evaluate the effectiveness of memantine in improving rehabilitation outcomes and preventing major depressive disorder in older adults who have been admitted to a rehabilitation hospital for a hip fracture or a cardiopulmonary condition. This double-blind study will last for 12 months. Participants will be randomly assigned to receive either placebo or memantine, which is a drug that is often used to treat Alzheimer's disease. Both memantine and placebo will be administered to participants for 12 weeks. All participants will be followed for an additional 40 weeks. Outcome measurements will include participants' depressive symptoms, motivation, and learned helplessness. In addition, medication side effects, functional outcome, and incidence of major depressive disorder will be measured. All measurements will be taken at Week 12 and Month 12.
Interventions
DRUGMemantine
Memantine dosage is started at 10 mg daily and is increased at Week 1 as tolerated to 10 mg two times a day.
OTHERPlacebo
Placebo distribution is planned to mimic the active drug.
Sponsors
National Institute of Mental Health (NIMH)
Eric Lenze
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Admission to a skilled nursing facility for rehabilitation within 3 months of recent disabling medical event (e.g., hip fracture) * Medically stable (e.g., no active seizures, delirium, unstable pulse/blood pressure)
Exclusion criteria
* Aphasia or cognitive impairments sufficiently severe to prevent valid assessment (e.g., a score of less than 22 on the Mini Mental State Examination) * Current major depressive episode * History of or current psychosis or mania * Current substance or alcohol abuse or dependence (within 3 months of study entry) * Current use of memantine * Sensitivity or contraindication to memantine * End-stage kidney, liver, heart, or lung disease * Recent hemorrhagic stroke * A FIM score of greater than 70 (on a 91 point scale)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Depressive Symptoms | week 0, week 12 | Hamilton depression rating scale ; scale ranges 0 (no symptoms) to 52 (severe depression) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Major Depressive Disorder | week 12 | cumulative incidence over 12 weeks of follow-up |
| Functional Recovery | week 0, week 12 | Functional Independence Msure, 13-item motor subscale (scale ranges 13-91, higher scores = better function) |
Countries
United States
Participant flow
Recruitment details
35 subjects were randomized
Pre-assignment details
No significant events. Please see Lenze et al, Int J of Geriatric Psychiatry 2012 article for details.
Participants by arm
| Arm | Count |
|---|---|
| Memantine (1) Memantine for 12 weeks
Memantine: Memantine dosage is started at 10 mg daily and is increased at Week 1 as tolerated to 10 mg two times a day. | 17 |
| Placebo (2) Placebo for 12 weeks
Placebo: Placebo distribution is planned to mimic the active drug. | 18 |
| Total | 35 |
Baseline characteristics
| Characteristic | Placebo (2) | Memantine (1) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 18 Participants | 17 Participants | 35 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 78 years STANDARD_DEVIATION 9.2 | 80.1 years STANDARD_DEVIATION 9.7 | 79.1 years STANDARD_DEVIATION 9.5 |
| Region of Enrollment United States | 18 participants | 17 participants | 35 participants |
| Sex: Female, Male Female | 14 Participants | 14 Participants | 28 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 17 | 0 / 18 |
| serious Total, serious adverse events | 0 / 17 | 0 / 18 |
Outcome results
Primary
Depressive Symptoms
Hamilton depression rating scale ; scale ranges 0 (no symptoms) to 52 (severe depression)
Time frame: week 0, week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Memantine (1) | Depressive Symptoms | Week 0 | 12.5 units on a scale | Standard Deviation 3.6 |
| Memantine (1) | Depressive Symptoms | Week 12 | 7 units on a scale | Standard Deviation 1.5 |
| Placebo (2) | Depressive Symptoms | Week 0 | 13.4 units on a scale | Standard Deviation 3.7 |
| Placebo (2) | Depressive Symptoms | Week 12 | 5.2 units on a scale | Standard Deviation 1.5 |
Comparison: Null: the two groups would not differ in depressive symptoms over time (ie both groups would improve equally in terms of their depressive symptoms) Power calculation: none; this was a pilot studyp-value: 0.42Mixed Models Analysis
Secondary
Functional Recovery
Functional Independence Msure, 13-item motor subscale (scale ranges 13-91, higher scores = better function)
Time frame: week 0, week 12
Population: intent to treat analysis; data presented are the week 12 data from the mixed effect model
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Memantine (1) | Functional Recovery | 73 units on a scale | Standard Error 7 |
| Placebo (2) | Functional Recovery | 81 units on a scale | Standard Error 6 |
Comparison: Null hypothesis: functional recovery would be the same in both groups. Power calculation: none. This was a pilot study.p-value: 0.06Mixed Models Analysis
Secondary
Incidence of Major Depressive Disorder
cumulative incidence over 12 weeks of follow-up
Time frame: week 12
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Memantine (1) | Incidence of Major Depressive Disorder | 3 Participants |
| Placebo (2) | Incidence of Major Depressive Disorder | 1 Participants |