Pioglitazone Adjunctive Therapy for Moderate-to-Severe Major Depressive Disorder: Randomized Double-Blind Placebo-Controlled Trial

• Published in: Neuropsychopharmacology (New York, N.Y.) N.Y.), 2012-08, Vol.37 (9), p.2093-2100
• Main Authors: SEPANJNIA, Khatereh, MODABBERNIA, Amirhossein, ASHRAFI, Mandana, MODABBERNIA, Mohammad-Jafar, AKHONDZADEH, Shahin
• Format: Article
• Language: English
• Subjects: Adult; Adult and adolescent clinical studies; Alzheimer's disease; Antidepressants; Biological and medical sciences; Chemotherapy, Adjuvant - psychology; citalopram; Citalopram - administration & dosage; Clinical trials; Depression; Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - psychology; Diabetes mellitus; Double-Blind Method; Drug Therapy, Combination; Drugs; Female; Follow-Up Studies; Humans; Inflammation; Insulin; Male; Medical sciences; Mental depression; Metabolic disorders; Metabolic syndrome; Mood disorders; Neuroprotection; Original; pioglitazone; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Remission; Severity of Illness Index; Side effects; thiazolidinediones; Thiazolidinediones - administration & dosage; Treatment Outcome; Variance analysis
• ISSN: 0893-133X; 1740-634X
• DOI: 10.1038/npp.2012.58

Thiazolidinediones have shown antidepressant effect in animal studies, as well as in some uncontrolled studies evaluating human subjects with concurrent major depressive disorder (MDD) and metabolic syndrome. Although these drugs are insulin sensitizers, they also have important anti-inflammatory, neuroprotective, and anti-excitotoxic properties. Thus, we hypothesized that they would show antidepressant effect in patients with MDD even if it was not accompanied by metabolic disturbances. In this double-blind placebo-controlled study, 40 patients with MDD (DSM-IV-TR) and Hamilton depression rating scale-17 (Ham-D) score ≥ 22 were randomized to citalopram plus pioglitazone (15 mg every 12 h) (n=20) or citalopram plus placebo (n=20) for 6 weeks. Patients were evaluated using Ham-D (weeks 0, 2, 4, 6). Repeated-measure analysis of variance (ANOVA) and analysis of covariance were used for comparison of scores between the two groups. Treatment response (≥ 50% reduction in Ham-D score), remission (Ham-D score ≤ 7), and early improvement (≥ 20% reduction in Ham-D score within the first 2 weeks) were compared between the two groups using Fisher's exact test. Pioglitazone showed superiority over placebo during the course of the trial (F(1, 38)=9.483, p=0.004). Patients in the pioglitazone group had significantly lower scores at all time points than the placebo group (P