Insulin Resistance in Patients With Mood Disorder

Not Applicable

Completed

Conditions: Depression
Bipolar Disorder
Insulin Resistance

Interventions: Drug: rosiglitazone

Registration Number: NCT00242619

Lead Sponsor: Stanford University

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 12

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Rosiglitzone	rosiglitazone	This group includes all 12 subjects who received rosiglitazone. Rosiglitazone was administered in addition to current antidepressant and/or mood-stabilizing medication at a dose of 4 mg/day for the first 4 weeks, with subsequent increase in dose to 9 mg/day for the remaining 8 weeks of the 12-week trial.

Primary Outcome Measures

Name	Time	Method
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.
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.

Secondary Outcome Measures