Riluzole in the Treatment of Bipolar Depression

Riluzole in the Treatment of Bipolar Depression: A Study of the Association Between Clinical Response and Change in Brain Glutamate Levels as Measured by Proton Magnetic Resonance Spectroscopy

Bipolar disorder is a common and often chronic and debilitating mental illness. The depressive phase of bipolar disorder contributes the largest portion of the disorder, and treatment resistant bipolar depression represents a significant public health problem. Recent research has suggested that bipolar depression is associated with elevated brain glutamate activity. We hypothesize that riluzole, a drug approved for ALS which inhibits glutamate activity, will lead to clinical improvement in patients with bipolar depression.

Study Overview

• Status: Completed
• Conditions: Bipolar Depression
• Intervention / Treatment: Drug: Riluzole

Detailed Description

We hypothesize that riluzole will lead to significant reduction in depressive symptoms as measured by the Hamilton Depression Rating Scale (HAM-D). Additionally, improvement in depressive symptoms will be associated with reduced glutamate levels in the anterior cingulate cortex, but not parieto-occipital cortex, both at day two and day 42.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Belmont, Massachusetts, United States, 02478
      • McLean Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female age 18-65
• Meets DSM-IV criteria for Bipolar Disorder and is currently depressed
• Current score of >/= 18 on the Hamilton Depression Scale

Exclusion Criteria:

• Active psychotic/manic symptoms
• Lifetime history of schizophrenia or obsessive compulsive disorder
• Clinically significant medical disease
• Women who are pregnant or lactating and women who are not using a medically accepted method of contraception.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Riluzole; Riluzole 50 mg twice daily for 2 weeks, increased to riluzole 50 mg in the morning and 100 mg in the evening for 1 week if tolerated, with a further increase to riluzole 100 mg twice daily if tolerated for 3 weeks.	Drug: Riluzole; 50 mg twice daily for 2 weeks 50 mg in the morning and 100 mg in the evening for 1 week 100 mg twice daily for 3 weeks; Other Names: Rilutek

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Hamilton Depression Rating Scale	The Hamilton Depression rating Scale is a clinician-rated scale that measures the severity of depression symptoms using 21 items. Minimum score is zero and maximum score is 65. Higher scores indicate more severe depressive symptoms.	Baseline (week 0) - week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montgomery Asberg Depression Rating Scale	The Montgomery-Asberg Depression Rating Scale is a clinician-rated scale that measures the severity of depression symptoms. The 10 items measured are apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Minimum score is zero and maximum score is 60. Higher scores represent more severe depressive symptoms.	Baseline (week 0) - week 6
Young Mania Rating Scale	The Young Mania Rating Scale is a clinician-rated scale that measures the severity of mania symptoms. The 11 items measures are elevated mood, increased motor activity, sexual interest, sleep, irritability, speech, language-thought disorder, thought content, aggressive behavior, appearance, and insight. Minimum score is zero and maximum score is 60. Higher scores represent more severe mania symptoms.	Baseline (week 0) - week 6
Clinical Global Impression Scale	The Clinical Global Impression Scale is a clinician-rated scale that evaluates the severity of illness at the time of assessment. The score ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill patients).	Baseline (week 0) - week 6

Collaborators and Investigators

• Sponsor: Mclean Hospital
• Investigators: Principal Investigator: Dost Ongur, M.D, Ph.D., McLean Hospital

Publications and helpful links

General Publications

• Brennan BP, Hudson JI, Jensen JE, McCarthy J, Roberts JL, Prescot AP, Cohen BM, Pope HG Jr, Renshaw PF, Ongur D. Rapid enhancement of glutamatergic neurotransmission in bipolar depression following treatment with riluzole. Neuropsychopharmacology. 2010 Feb;35(3):834-46. doi: 10.1038/npp.2009.191. Epub 2009 Dec 2.

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Actual): June 1, 2009
• Study Completion (Actual): July 1, 2009

Study Registration Dates

• First Submitted: October 12, 2007
• First Submitted That Met QC Criteria: October 12, 2007
• First Posted (Estimate): October 16, 2007

Study Record Updates

• Last Update Posted (Actual): August 7, 2018
• Last Update Submitted That Met QC Criteria: August 6, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: depression; Bipolar
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Bipolar and Related Disorders; Depression; Depressive Disorder; Bipolar Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Neuroprotective Agents; Protective Agents; Anticonvulsants; Riluzole
• Other Study ID Numbers: 2007-P-000751