Creatine Monohydrate as Adjuvant Therapy for Bipolar Depression

A Double-Blind, Randomized, Placebo-Controlled Clinical Trial to Evaluate the Efficacy of Creatine Monohydrate as Adjunctive Therapy for Bipolar Depression

The purpose of this study is to determine whether creatine monohydrate is effective as an adjuvant treatment for bipolar depression.

Study Overview

• Status: Completed
• Conditions: Bipolar I Disorder; Current Episode Depressed
• Intervention / Treatment: Dietary supplement: placebo; Dietary supplement: creatine monohydrate

Detailed Description

Bipolar Depression is associated with high rates of disability and increased mortality. Despite its major negative impact, treatment of Bipolar Depression is still controversial and only partially efficacious, with over half of patients not responding adequately to available treatment. In this context, the use of drugs that modulate energy metabolism has been proposed as promising new option as treatment strategies for bipolar depression. The aim of our proposed study is to perform a 6-week randomized, double-blind, placebo-controlled clinical trial of creatine monohydrate as an adjuvant treatment for bipolar depression.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • SP
    • Sao Paulo, SP, Brazil, 01060-970
      • Institute of Psychiatry - HC-FMUSP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Individuals eligible for the study will be adults aged 18 to 60 years of age who met DSM-IV criteria assessed by the SCID (Structural Clinical Interview for DSM-IV) for type I bipolar disorder, current episode depressed.
• Patients who have scored > 19 on the Montgomery-Asberg Depression Rating Scale (MADRS) will be included, although more than two weeks of treatment with lithium (serum level> 0.8 mEq / L), valproate (serum levels> 50 mg / L) or quetiapine (300-600mg/dia dose) or drug combination.
• Antipsychotics, anticonvulsants, benzodiazepines, and thyroid supplementation will be allowed if the dose has remained stable over the past two weeks.
• Antidepressants will be allowed if the dosage has remained stable for 4 weeks.

Exclusion Criteria:

• Subjects with substance abuse within 2 weeks before inclusion or substance dependence up to 2 months will not be included.

• Other exclusion criteria will be:

  • diagnosis of schizophrenia,
  • dementia,
  • delirium,
  • epilepsy,
  • mental retardation,
  • clinically unstable medical illnesses,
  • preexisting renal disease,
  • history of hypersensibility to creatine.
• Not included are individuals at high risk for suicidal or homicidal behavior or self-mutilation will not be included.
• Women with gestational potential can only be included if they are using reliable contraception.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: creatine monohydrate; 6g qd for 6 weeks	Dietary supplement: creatine monohydrate
Placebo Comparator: placebo; 6g qd for 6 weeks	Dietary supplement: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MADRS (Montgomery-Asberg Depression Rating Scale)	change of score on the Montgomery-Asberg Depression Rating Scale	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HDRS-17 (Hamilton Depression Rating Scale - 17-item version)	change of score on the Hamilton Depression Rating Scale - 17-item version	6 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
CGI (Clinical Global Impressions Scale) - Severity and Improvement	change of score on the Clinical Global Impressions Scale	6 weeks
YMRS (Young Mania Rating Scale)	change of score on the Young Mania Rating Scale	6 weeks

Collaborators and Investigators

• Sponsor: University of Sao Paulo
• Investigators: Principal Investigator: Beny Lafer, PhD, Bipolar Disorder Research Program, Coordinator, IPq-HC-FMUSP

Publications and helpful links

General Publications

• Toniolo RA, Silva M, Fernandes FBF, Amaral JAMS, Dias RDS, Lafer B. A randomized, double-blind, placebo-controlled, proof-of-concept trial of creatine monohydrate as adjunctive treatment for bipolar depression. J Neural Transm (Vienna). 2018 Feb;125(2):247-257. doi: 10.1007/s00702-017-1817-5. Epub 2017 Nov 24.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2012
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: July 29, 2012
• First Submitted That Met QC Criteria: July 31, 2012
• First Posted (Estimated): August 1, 2012

Study Record Updates

• Last Update Posted (Estimated): December 5, 2023
• Last Update Submitted That Met QC Criteria: December 1, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Bipolar and Related Disorders; Bipolar Disorder
• Other Study ID Numbers: CR-BD-RCT