Pioglitazone as an Adjunct for Moderate to Severe Depressive Disorder

Overview

The purpose of this study is to determine whether Pioglitazone as an adjunct to Citalopram is effective in treatment of moderate to severe depression

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Double (Participant, Outcomes Assessor)
  • Study Primary Completion Date: October 2011

Detailed Description

Pioglitazone as a Ppar-gamma agonist is an anti diabetic drug. It was also shown that, it has certain anti inflammatory and neuro-protective effects. In recent years it has been proposed that Ppar-gamma agonists may have effects on mood and cognition. In animal studies and in one human case report as well as a pilot study on human subjects these drugs improved symptoms of depression. A randomized controlled and double blind design will provide further evidence for the efficacy of these drugs in major depressive disorder.

Interventions

  • Drug: Pioglitazone+Citalopram+Chlordiazepoxide
    • Pioglitazone 15 mg every 12 hours for six weeks Citalopram 20 mg per day for week one, and then 30 mg/day for 5 consecutive weeks. Chlordiazepoxide 10 mg each night for first three weeks
  • Drug: Placebo+ Citalopram+ Chlordiazepoxide
    • Placebo 1 Q12h for 6 weeks with the same shape and color as Pioglitazone. Citalopram 20 mg per day for week one, and then 30 mg/day for 5 consecutive weeks. Chlordiazepoxide 10 mg each night for first three weeks

Arms, Groups and Cohorts

  • Active Comparator: Pioglitazone+Citalopram+Chlordiazepoxide
    • Pioglitazone 15 mg Q12h will be given to the patients in active comparator group for 6 weeks. Citalopram 20 mg per day for week one, and then 30 mg/day for 5 consecutive weeks.Chlordiazepoxide 10 mg/day for first three weeks
  • Placebo Comparator: Placebo+ Citalopram+ Chlordiazepoxide
    • Placebo 1 Q12h for 6 weeks with the same shape and color as Pioglitazone. Citalopram 20 mg per day for week one, and then 30 mg/day for 5 consecutive weeks. Chlordiazepoxide 10 mg each night for first three weeks.

Clinical Trial Outcome Measures

Primary Measures

  • Scores of Hamilton Depression Rating Scale (17 items) at the end
    • Time Frame: week 6
    • Hamilton Depression rating scale is a 17-item scale. The questionnaire rates the severity of symptoms observed in depression such as low mood, insomnia, agitation, anxiety and weight loss. The questionnaire is presently one of the most commonly used scales for rating depression in medical research. The primary outcome measure is Scores on Hamilton Depression Rating Scale at the end (week 6)

Secondary Measures

  • Number of Adverse events in each group
    • Time Frame: week 2,4,6
  • Scores of Hamilton Depression Rating Scale (17 items)
    • Time Frame: week 0,2,4

Participating in This Clinical Trial

Inclusion Criteria

  • Diagnosis of Major depressive disorder based on DSM-IV TR criteria – Age 18-50 – Hamilton Depression Rating scale >=22 – Signing the informed consent form – Citalopram be the drug of choice for the patient irrespective of other eligibility criteria Exclusion Criteria:

  • Problems in other Axes – Pregnancy and lactation – Serious or life threatening disease – taking other antidepressant in the recent month or Electroconvulsive shock in the recent two months, and taking other psychotropic agents – Diabetes controlled with drugs or insulin (patients with only lifestyle interventions will be included), Liver disease, Congestive heart failure Class III and IV – Metabolic syndrome

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 50 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Tehran University of Medical Sciences
  • Provider of Information About this Clinical Study
    • Principal Investigator: Amirhossein Modabbernia, Dr Amirhossein Modabbernia – Tehran University of Medical Sciences
  • Overall Official(s)
    • Shahin Akhondzadeh, PhD, Study Chair, Tehran University of Medical Sciences

References

Kemp DE, Ismail-Beigi F, Calabrese JR. Antidepressant response associated with pioglitazone: support for an overlapping pathophysiology between major depression and metabolic syndrome. Am J Psychiatry. 2009 May;166(5):619. doi: 10.1176/appi.ajp.2008.08081195.

Rasgon NL, Kenna HA, Williams KE, Powers B, Wroolie T, Schatzberg AF. Rosiglitazone add-on in treatment of depressed patients with insulin resistance: a pilot study. ScientificWorldJournal. 2010 Feb 19;10:321-8. doi: 10.1100/tsw.2010.32.

Rosa AO, Kaster MP, Binfaré RW, Morales S, Martín-Aparicio E, Navarro-Rico ML, Martinez A, Medina M, García AG, López MG, Rodrigues AL. Antidepressant-like effect of the novel thiadiazolidinone NP031115 in mice. Prog Neuropsychopharmacol Biol Psychiatry. 2008 Aug 1;32(6):1549-56. doi: 10.1016/j.pnpbp.2008.05.020. Epub 2008 Jun 25.

Eissa Ahmed AA, Al-Rasheed NM, Al-Rasheed NM. Antidepressant-like effects of rosiglitazone, a PPARγ agonist, in the rat forced swim and mouse tail suspension tests. Behav Pharmacol. 2009 Oct;20(7):635-42. doi: 10.1097/FBP.0b013e328331b9bf.

Citations Reporting on Results

Sepanjnia K, Modabbernia A, Ashrafi M, Modabbernia MJ, Akhondzadeh S. Pioglitazone adjunctive therapy for moderate-to-severe major depressive disorder: randomized double-blind placebo-controlled trial. Neuropsychopharmacology. 2012 Aug;37(9):2093-100. doi: 10.1038/npp.2012.58. Epub 2012 May 2.

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