Bipolar Disorder, Depression, Insulin Resistance
Conditions
Brief summary
Insulin resistance is known to be associated with mood disorders and cognitive difficulties. The purpose of this study is to treat depressed patients with rosiglitazone (also known as \[AKA\] Avandia), therefore improving glucose sensitivity, which in turn has the potential to affect mood and thinking. We, the researchers at Stanford University, are recruiting men and women who have been diagnosed with depression, and are willing to participate in this 3 month study. Participation involves neuropsychological testing, 2 blood draws called an oral glucose tolerance test (OGTT), which tests for glucose and insulin levels, and the medication, rosiglitazone. Participants are allowed to continue on their current psychiatric medication.
Detailed description
An association between insulin resistance (IR) and affective disorders has been postulated in a number of cross-sectional studies. Limited data exist on potential changes in IR associated with improvement in depressive symptoms and/or depression remission resolution - two studies reported decreased IR after successful antidepressant treatment, while another study reported persisting IR even after successful treatment. We have postulated that IR is a part of the pathophysiology of affective disorders, and its improvement (via pharmacological or nonpharmacological treatments) may significantly reduce the severity of depressive symptoms. In support of this hypothesis, we previously reported increased IR in women with bipolar disorder, as well as a significant association between IR and depressive symptoms in women with primary IR syndrome (polycystic ovary syndrome \[PCOS\]). In the current pilot study, we attempted a more direct testing of the hypothesis that improvement of IR will result in improvement in mood in patients with depressive disorders. The aim of the study was to evaluate whether addition of the peroxisome proliferator-activated receptor-γ (PPAR) agonist rosiglitazone to the treatment as usual (TAU) of nondiabetic patients with unipolar or bipolar depression would result in improvement in depression severity and clinical global impression (CGI). Insulin sensitizing agents have proven efficacious in nondiabetic IR, or prediabetic, individuals. All subjects in this pilot study had elevated fasting plasma glucose (FPG) and ratios of high density lipoproteins (HDL) to triglycerides (TG), which are established surrogate markers of IR. In the current pilot study, we attempted a more direct testing of the hypothesis that improvement of IR will result in improvement in mood in patients with depressive disorders. The aim of the study was to evaluate whether addition of the peroxisome proliferator-activated receptor-γ (PPAR) agonist rosiglitazone to the treatment as usual (TAU) of nondiabetic patients with unipolar or bipolar depression would result in improvement in depression severity and clinical global impression (CGI). Insulin sensitizing agents have proven efficacious in nondiabetic IR, or prediabetic, individuals. All subjects in this pilot study had elevated fasting plasma glucose (FPG) and ratios of high density lipoproteins (HDL) to triglycerides (TG), which are established surrogate markers of IR.
Interventions
DRUGrosiglitazone
Rosiglitazone was administered at two different doses over the 12-week period.
Sponsors
Stanford University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
- Current depression * Insulin resistance * Current physician/psychiatrist care * Between the ages of 18-60 * Willing to sign the Human Subjects Protection Consent Form * Willing to have blood sampling
Exclusion criteria
- Diabetes * History of unstable heat disease * Uncontrolled hypertension * Extensive use of alcohol * Current use of street drugs * History of myocardial infarction * History of cerebrovascular disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hamilton Depression Rating Scale (HDRS-21) | 12 weeks | The Hamilton Depression Rating Scale (HDRS-21) measures depression severity on a scale from 0 to 21, with 0 being the lowest level of depression severity and 21 being the highest level of depression severity. |
| Clinical Global Impression-Severity Scale (CGI-S) | 12 weeks | The Clinical Global Impression-Severity Scale (CGI-S) assesses depression severity. It is a 7-point scale, where 1 is the lowest level of depression severity and 7 is the highest level of depression severity. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Completers Subjects who met all criteria, took rosiglitazone, and completed the study. | 8 |
| Drop-Outs Subjects who met all criteria, took rosiglitazone, and did not complete the study. | 4 |
| Total | 12 |
Baseline characteristics
| Characteristic | Drop-Outs | Completers | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 8 Participants | 12 Participants |
| Age, Continuous | 52.0 years STANDARD_DEVIATION 6.5 | 51.9 years STANDARD_DEVIATION 5.6 | 51.95 years STANDARD_DEVIATION 6.05 |
| Gender Female | 4 Participants | 7 Participants | 11 Participants |
| Gender Male | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment United States | 4 participants | 8 participants | 12 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 8 | 0 / 4 |
| serious Total, serious adverse events | 0 / 8 | 0 / 4 |
Outcome results
Primary
Clinical Global Impression-Severity Scale (CGI-S)
The Clinical Global Impression-Severity Scale (CGI-S) assesses depression severity. It is a 7-point scale, where 1 is the lowest level of depression severity and 7 is the highest level of depression severity.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Completers | Clinical Global Impression-Severity Scale (CGI-S) | 4.1 units on a scale | Standard Deviation 0.6 |
| Drop-Outs | Clinical Global Impression-Severity Scale (CGI-S) | 3.3 units on a scale | Standard Deviation 0.5 |
Primary
Hamilton Depression Rating Scale (HDRS-21)
The Hamilton Depression Rating Scale (HDRS-21) measures depression severity on a scale from 0 to 21, with 0 being the lowest level of depression severity and 21 being the highest level of depression severity.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Completers | Hamilton Depression Rating Scale (HDRS-21) | 19.9 units on a scale | Standard Deviation 5 |
| Drop-Outs | Hamilton Depression Rating Scale (HDRS-21) | 13.0 units on a scale | Standard Deviation 0.8 |