Bipolar Depression
Conditions
Keywords
Bipolar depression, elderly, Coenzyme Q10, Magnetic resonance spectroscopy
Brief summary
We propose to study and compare measures of brain energy metabolism in geriatric bipolar individuals and healthy older adults. We would also like to investigate changes in brain energy metabolites and in vivo creatine kinase (CK) enzymatic activity associated with CoQ10 administration in older bipolar individuals.
Detailed description
Hypotheses 1. At baseline, the forward rate constant (kfor) of CK enzymatic activity in the frontal lobe of older subjects with bipolar depression will be significantly decreased relative to that of age-matched healthy controls. 2. After 8 weeks of treatment, bipolar depression subjects will demonstrate an increase in the kfor of CK after 8 weeks of CoQ 10 treatment. 3. Increases in the CK forward rate constant (kfor) will correlate with improvement in subjects' mood state as assessed by the Montgomery Asberg Depression Rating Scale (MADRS). 4. Baseline measures of executive functioning and information processing speed (measured by performance on the Wisconsin Card Sorting Test (WCST), Trails A and B and Stroop tests) will be impaired in subjects with geriatric bipolar depression compared with healthy controls. These measures will improve with successful treatment with CoQ10 and correlate with increases in the CK forward rate constant (kfor). Summary: A review of literature suggests a distinct pattern of bioenergetic changes, possibly related to mitochondrial dysfunction and abnormal CK function, in older adults and in individuals with bipolar disorder. As opposed to rudimentary measurements of static metabolite concentrations, the novel use of MT-MRS in such individuals will offer insight into the enzyme kinetics of CK, specifically examining the rate at which ATP is formed from PCr. From previous investigations it would seem that the dietary-supplement, CoQ10, is able to improve the efficiency of mitochondrial function in subjects with altered bioenergetics. We propose to measure CK activity and PCr turnover rate before and after CoQ10 treatment, with the overall aim of understanding metabolic relationships between brain bioenergetic alterations and treatment with CoQ10 in geriatric bipolar depression.
Interventions
DRUGCoEnzyme Q10
CoEnzyme Q10 with dosage range from 400 mg to 1200 mg per day
Sponsors
National Alliance for Research on Schizophrenia and Depression
Mclean Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
55 Years to 89 Years
Healthy volunteers
Yes
Inclusion criteria
* 55 years or older * Meet DSM-IV diagnostic criteria for Bipolar Disorder, Current Episode Depressed * Montgomery Asberg Depression Rating Scale (MADRS) Score of \>20 * If the MADRS score is \<20 but \>16, a diagnosis of bipolar disorder, current episode depressed, based on the Structured Clinical Interview of DSM IV TR (SCID) and Dr. Forester's initial interview would allow the subject to be included in the study. * Young Mania Rating Scale (YMRS) Score of \< 6 * If the YMRS score is \>6 subjects can still be admitted if subjects do not meet clinical criteria for mania or hypomania at the time of screening * Able to provide informed consent * Must speak English * Must be able to visit McLean Hospital for the screening visit and six study visits during the 8-week duration of the study * Subjects may be taking other medications for bipolar depression including antidepressants, mood stabilizers and antipsychotic mediations prior to Co-Q10 therapy, but may not have any dosage adjustments of these medications in the week before Co-Q10 is added.
Exclusion criteria
* 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, unipolar major depressive disorder, patients with substance dependence disorders, including alcohol, active within the last 12 months. * History of drug hypersensitivity or intolerance to Coenzyme Q10. * Use of medications that are excluded in this study (barbiturates; however, the use of non-benzodiazepine sedative hypnotics (such as zolpidem (Ambien)) may be used as needed except within 12 hours of the MRI scan) * Benzodiazepines may be used by subjects throughout the study as long as they are not taken within 12 hours of any MRI scan. * Subjects diagnosed with a mitochondrial disorder. * Subjects taking other putative mitochondrial enhancers (e.g., vitamin E, carnitine, creatine, Vitamin complex B, pramipexole) at the time of study entry. * Any of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| We Measured the Change in Rate Constant of Creatine Kinase in Individuals With Bipolar Depression Treated With CoQ 10 as Compared With Age and Gender Matched Controls. These Rate Constants Were Calculated Using Magnetic Resonance Imaging (MRI). | 8 week trial | The rate constant for creatine kinase is a measurement of the reaction rate ADP+PCr \<---\> ATP + Cr, which is catalyzed by the enzyme creatine kinase. The rate constant shows the direction and magnitude of the reaction at equilibrium. A higher rate constant indicates a higher rate constant of the CK enzyme, meaning, more efficient/rapid conversion of PCr to ATP through the creatine kinase enzymatic reaction in tissues with high and fluctuating energy demands such as brain and muscle tissue. As the value is a reaction rate, there are no associated units. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| We Measured Response to Treatment of Depression (Using the Montgomery Asberg Depression Rating Scale)in Older Adults With Bipolar Disorder After an 8 Week Trial of CoQ10. | 8 week trial | The Montgomery Asberg Depression Rating Scale (MADRS) is a 10 question questionnaire which assesses symptom severity of depression. The score is on a 0-60 scale with higher numbers indicating more severe depressive symptoms. The score is represented as a number of points. Clinical improvement following treatment with CoQ10 supplement was only tested in the Bipolar subject cohort, not in healthy controls, therefore outcome data only apply to the bipolar group. |
Countries
United States
Participant flow
Recruitment details
Please note that subjects who sign the informed consent form are considered enrolled. Only subjects who met eligibility following screening are included in analyses and thus included in the participant flow. Of the 42 enrolled, 19 started the study and 18 completed.
Participants by arm
| Arm | Count |
|---|---|
| CoQ10 Subjects were given open-label, adjunct treatment with CoQ10 with oral dosing between 400-1200mg per day. Dosing was started at 400mg and titrated up to 1200mg as tolerated. This value does not match the value of subjects enrolled because only subjects who were not screen failures are included in this group. | 11 |
| Healthy Controls Healthy age matched control subjects do not receive treatment. Controls undergo testing and MRIs to serve as comparison group. This value does not match the value of subjects enrolled because only subjects who were not screen failures are included in this group. | 8 |
| Total | 19 |
Baseline characteristics
| Characteristic | Healthy Controls | CoQ10 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 3 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 8 Participants | 13 Participants |
| Age, Continuous | 66.4 years STANDARD_DEVIATION 9.5 | 63.4 years STANDARD_DEVIATION 7.5 | 64.6 years STANDARD_DEVIATION 8.3 |
| Region of Enrollment United States | 8 participants | 11 participants | 19 participants |
| Sex: Female, Male Female | 4 Participants | 7 Participants | 11 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 11 | 2 / 8 |
| serious Total, serious adverse events | 0 / 11 | 1 / 8 |
Outcome results
Primary
We Measured the Change in Rate Constant of Creatine Kinase in Individuals With Bipolar Depression Treated With CoQ 10 as Compared With Age and Gender Matched Controls. These Rate Constants Were Calculated Using Magnetic Resonance Imaging (MRI).
The rate constant for creatine kinase is a measurement of the reaction rate ADP+PCr \<---\> ATP + Cr, which is catalyzed by the enzyme creatine kinase. The rate constant shows the direction and magnitude of the reaction at equilibrium. A higher rate constant indicates a higher rate constant of the CK enzyme, meaning, more efficient/rapid conversion of PCr to ATP through the creatine kinase enzymatic reaction in tissues with high and fluctuating energy demands such as brain and muscle tissue. As the value is a reaction rate, there are no associated units.
Time frame: 8 week trial
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CoQ10 | We Measured the Change in Rate Constant of Creatine Kinase in Individuals With Bipolar Depression Treated With CoQ 10 as Compared With Age and Gender Matched Controls. These Rate Constants Were Calculated Using Magnetic Resonance Imaging (MRI). | 0.02 per second | Standard Deviation 0.002 |
| Healthy Controls | We Measured the Change in Rate Constant of Creatine Kinase in Individuals With Bipolar Depression Treated With CoQ 10 as Compared With Age and Gender Matched Controls. These Rate Constants Were Calculated Using Magnetic Resonance Imaging (MRI). | 0.03 per second | Standard Deviation 0.05 |
Secondary
We Measured Response to Treatment of Depression (Using the Montgomery Asberg Depression Rating Scale)in Older Adults With Bipolar Disorder After an 8 Week Trial of CoQ10.
The Montgomery Asberg Depression Rating Scale (MADRS) is a 10 question questionnaire which assesses symptom severity of depression. The score is on a 0-60 scale with higher numbers indicating more severe depressive symptoms. The score is represented as a number of points. Clinical improvement following treatment with CoQ10 supplement was only tested in the Bipolar subject cohort, not in healthy controls, therefore outcome data only apply to the bipolar group.
Time frame: 8 week trial
Population: Clinical improvement following treatment with CoQ10 supplement was only tested in the Bipolar subject cohort, not in healthy controls, therefore outcome data only apply to the bipolar group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CoQ10 | We Measured Response to Treatment of Depression (Using the Montgomery Asberg Depression Rating Scale)in Older Adults With Bipolar Disorder After an 8 Week Trial of CoQ10. | Pre-Treatment (baseline) | 21.4 units on a scale | Standard Deviation 5.5 |
| CoQ10 | We Measured Response to Treatment of Depression (Using the Montgomery Asberg Depression Rating Scale)in Older Adults With Bipolar Disorder After an 8 Week Trial of CoQ10. | Post-Treatment (week 8) | 18.4 units on a scale | Standard Deviation 7.3 |