Treatment Resistant Geriatric Depression in Primary Care

• Status: Completed
• Trial end date: 2012-04-01
• Target enrollment: 0
• Participant gender: All

Summary

This study involves collaboration between McLean Hospital, Geriatric Medicine at the Cambridge Health Alliance (CHA) and other sites within the Partners and Harvard Medical School network. The investigators plan to recruit individuals 55 to 89 years old with treatment resistant depression. Someone with "treatment resistant" depression for this study may be someone who still has sad or low feelings and thoughts even though he/she is taking an antidepressant medication for at least 8 weeks to help relieve his/her depression. During the study, subjects will gradually add memantine hydrochloride in dosages up to 20 mg/day for 8 weeks to their standard antidepressant treatment.

The investigators are doing this research study to help answer 3 questions:

1. Do older adults with treatment resistant Major Depression have lower levels of a chemical in the brain called NAAG than older adults without Major Depression?

2. Do older adults with naturally low NAAG levels do better on memantine hydrochloride treatment than older adults with higher amounts of this chemical on memantine hydrochloride treatment?

3. Do older adults with treatment resistant depression have more problems with memory and concentration than older adults without depression?

The investigators are also interested in looking at electrical and neuronal activity of the brain, spiritual beliefs, and fatigue in relationship to depression.

The investigators hypothesize that:

1. Older individuals with treatment resistant Major Depression will have lower levels of NAAG compared with age-matched older control subjects.

2. Older adults with treatment resistant depression and low NAAG levels will do better on treatment with memantine hydrochloride than older adults on memantine with higher NAAG levels.

3. Older adults with depression will do better on tests of attention and executive functioning after treatment with memantine hydrochloride.

4. Healthy controls will do better on tests of attention and executive functioning than older adults with depression.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Mclean Hospital
• Collaborators: Cambridge Health Alliance; Harvard University
• Treatments: Memantine; N-acetyl-1-aspartylglutamic acid

Criteria

Inclusion Criteria for Depression Subjects:

• Ability to provide informed consent

• Age 55 to 89, inclusive

• DSM-IV Diagnosis of Major Depressive Disorder

• MADRS score of >16 at screening and baseline*

• Must speak, read, and write in English

• On standard antidepressant medication for at least 8 weeks prior to beginning memantine hydrochloride treatment

Exclusion Criteria for Depression Subjects:

• Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease

• History of seizure disorder

• History or current diagnosis of the following psychiatric illnesses: any organic mental disorder (including dementia), schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorder not otherwise specified, bipolar disorder, patients with substance dependence disorders, including alcohol, active within the last 12 months

• History of drug hypersensitivity or intolerance to memantine hydrochloride

• Use of the following class of medications: barbiturates.**

• Inability to complete the screening procedures

• Contraindications to magnetic resonance imagining (MRI), including any of the exclusion criteria mentioned in the MRI risks section of this protocol

• MRI abnormality that compromises integrity of imaging data (eg. intracranial lesions, hydrocephalus)

• Non-English speaking participants

Notes for Study Criteria (Depressed Subjects):

*Depressed subjects that score below a 16 on the MADRS at baseline may be reevaluated within two weeks. After reevaluation, study staff will exclude subjects that continue to score below a 16 on the MADRS. All subjects who score 16 or above at reevaluation may be included in the study at that point, provided they still meet study criteria.

**Benzodiazepines and non-benzodiazepine sedative hypnotics (such as zolpidem/Ambien), may be used by depressed subjects throughout the study as long as they are not taken within 12 hours of any MRI scan.

Inclusion Criteria for Control Subjects:

• Ability to provide informed consent

• Age 55 to 89, inclusive

• MADRS score <4

• Must speak, read, and write in English

• Must match with a depression subject previously enrolled on age (+/- 5 years) and sex

Exclusion Criteria for Control Subjects:

• Any evidence of current or past psychiatric disorders

• Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease

• History of seizure disorder

• History or current diagnosis of the following psychiatric illnesses: any organic mental disorder (including dementia), major depressive disorder, depression NOS, dysthymia, bipolar disorder( type I or II), schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorder not otherwise specified, bipolar major depressive disorder, patients with substance dependence disorders, including alcohol.

• Use of any class of psychotropic medication.

• Inability to complete the screening visit

• MRI abnormality that compromises integrity of imaging data

• Contraindications to magnetic resonance imagining (MRI), including any of the exclusion criteria mentioned in the MRI risks section of this protocol

• Non-English speaking participants