TY - JOUR
T1 - Use of insulin sensitizers for the treatment of major depressive disorder
T2 - A pilot study of pioglitazone for major depression accompanied by abdominal obesity
AU - Kemp, David E.
AU - Ismail-Beigi, Faramarz
AU - Ganocy, Stephen J.
AU - Conroy, Carla
AU - Gao, Keming
AU - Obral, Sarah
AU - Fein, Elizabeth
AU - Findling, Robert L.
AU - Calabrese, Joseph R.
N1 - Funding Information:
Dr. Ganocy receives grant support from AstraZeneca and Eli Lilly.
Funding Information:
Funding for this study was provided in part by NIH grant 1KL2RR024990 to Dr. Kemp. The project described was supported by Grant Number UL1 RR024989 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). The content of this article is solely the responsibility of the authors and does not necessarily represent the official view of NCRR or NIH. Takeda Pharmaceuticals Inc. supplied the study medication for use in this trial.
PY - 2012/2
Y1 - 2012/2
N2 - Objective: This study was conducted to examine the safety and efficacy of pioglitazone, a thiazolidinedione insulin sensitizer, in adult outpatients with major depressive disorder. Method: In a 12-week, open-label, flexible-dose study, 23 patients with major depressive disorder received pioglitazone monotherapy or adjunctive therapy initiated at 15 mg daily. Subjects were required to meet criteria for abdominal obesity (waist circumference > 35 in. in women and > 40 in. in men) or metabolic syndrome. The primary efficacy measure was the change from baseline to Week 12 on the Inventory of Depressive Symptomatology (IDS) total score. Partial responders (≥25% decrease in IDS total score) were eligible to participate in an optional extension phase for an additional three months. Results: Pioglitazone decreased depression symptom severity from a total IDS score of 40.3 ± 1.8 to 19.2 ± 1.8 at Week 12 (p <.001). Among partial responders (≥25% decrease in IDS total score), an improvement in depressive symptoms was maintained during an additional 3-month extension phase (total duration = 24 weeks) according to IDS total scores (p <.001). Patients experienced a reduction in insulin resistance from baseline to Week 12 according to the log homeostasis model assessment (- 0.8 ± 0.75; p <.001) and a significant reduction in inflammation as measured by log highly- sensitive C-reactive protein (- 0.87 ± 0.72; p <.001). During the current episode, the majority of participants (74%, n = 17), had already failed at least one antidepressant trial. The most common side effects were headache and dizziness; no patient discontinued due to side effects. Limitations: These data are limited by a small sample size and an open-label study design with no placebo control. Conclusion: Although preliminary, pioglitazone appears to reduce depression severity and improve several markers of cardiometabolic risk, including insulin resistance and inflammation. Larger, placebo-controlled studies are indicated.
AB - Objective: This study was conducted to examine the safety and efficacy of pioglitazone, a thiazolidinedione insulin sensitizer, in adult outpatients with major depressive disorder. Method: In a 12-week, open-label, flexible-dose study, 23 patients with major depressive disorder received pioglitazone monotherapy or adjunctive therapy initiated at 15 mg daily. Subjects were required to meet criteria for abdominal obesity (waist circumference > 35 in. in women and > 40 in. in men) or metabolic syndrome. The primary efficacy measure was the change from baseline to Week 12 on the Inventory of Depressive Symptomatology (IDS) total score. Partial responders (≥25% decrease in IDS total score) were eligible to participate in an optional extension phase for an additional three months. Results: Pioglitazone decreased depression symptom severity from a total IDS score of 40.3 ± 1.8 to 19.2 ± 1.8 at Week 12 (p <.001). Among partial responders (≥25% decrease in IDS total score), an improvement in depressive symptoms was maintained during an additional 3-month extension phase (total duration = 24 weeks) according to IDS total scores (p <.001). Patients experienced a reduction in insulin resistance from baseline to Week 12 according to the log homeostasis model assessment (- 0.8 ± 0.75; p <.001) and a significant reduction in inflammation as measured by log highly- sensitive C-reactive protein (- 0.87 ± 0.72; p <.001). During the current episode, the majority of participants (74%, n = 17), had already failed at least one antidepressant trial. The most common side effects were headache and dizziness; no patient discontinued due to side effects. Limitations: These data are limited by a small sample size and an open-label study design with no placebo control. Conclusion: Although preliminary, pioglitazone appears to reduce depression severity and improve several markers of cardiometabolic risk, including insulin resistance and inflammation. Larger, placebo-controlled studies are indicated.
KW - Insulin resistance
KW - Major depressive disorder
KW - Metabolic syndrome
KW - Pioglitazone
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U2 - 10.1016/j.jad.2011.06.033
DO - 10.1016/j.jad.2011.06.033
M3 - Article
C2 - 21782251
AN - SCOPUS:84857367138
SN - 0165-0327
VL - 136
SP - 1164
EP - 1173
JO - Journal of Affective Disorders
JF - Journal of Affective Disorders
IS - 3
ER -