Add-on Dextromethorphan in Bipolar Disorders (DM)

Dextromethorphan Enhances the Therapeutic Efficacy of Valoproate in Bipolar Disorder Patients

Dextromethorphan has been reported affording neuroprotection on dopaminergic neurons and having protective effect against inflammation-related neuron damage. These anti-inflammatory and neuroprotective effects of dextromethorphan would suggest potential clinical benefits of dextromethorphan add-on therapy to valproate for bipolar disorder patients. This hypothesis was based on the findings that the mood stabilizers have been reported to be neuroprotective through the release of neurotrophic factors such as GDNF from astroglia. Thus, the combination treatment of mood stabilizers and dextromethorphan might improve the therapeutic efficacy for bipolar disorder patients.

Study Overview

• Status: Completed
• Conditions: Bipolar Disorder
• Intervention / Treatment: Drug: Valproate; Drug: Dextromethorphan 30 mg; Drug: Dextromethorphan 60 mg per day; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Phase 3

Contacts and Locations

Study Locations

• Taiwan
  • Tainan, Taiwan, 704
    • Ru-Band Lu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female patient aged ≧18 and ≦65 years.
2. A diagnosis of bipolar I or II disorder according to DSM-IV criteria made by a specialist in psychiatry.
3. A total of HDRS score at least 18 or YMRS score at least 14 at screen.
4. Signed informed consent by patient or legal representative
5. Patient or a reliable caregiver can be expected to ensure acceptable compliance and visit attendance for the duration of the study.

Exclusion Criteria:

1. Women of childbearing potential not using adequate contraception as per investigator judgment or not willing to comply with contraception for duration of study.
2. Females who are pregnant or nursing.
3. Patient has received dextromethorphan, or other selective cyclo- oxygenase 2 (Cox-2) inhibitors, or other anti-inflammatory medication within 1 week prior to first dose of double-blind medication.
4. Axis-I DSM-IV diagnosis other than bipolar I or II disorder.
5. Current evidence of an uncontrolled and/or clinically significant medical condition (e.g., cardiac, hepatic and renal failure), which in the judgments of the investigator, would compromise patient safety or preclude study participation.
6. History of intolerance to valproate or dextromethorphan or other Cox-2 inhibitors.
7. History of sensitivity reaction (e.g., urticaria, angioedema, bronchospasm, severe rhinitis, anaphylactic shock) precipitated by dextromethorphan.
8. Patient has received electroconvulsive therapy (ECT) within 4 weeks prior to first dose of doubleblind medication.
9. Diagnosis of or treatment for esophageal, gastric, pyloric channel, or duodenal ulceration or related complications (bleeding and/or perforation) within 30 days prior to receiving first dose of double-blind medication.
10. Inclusion in another bipolar disorder study or study for another indication with psychotropic's within the last 30 days prior to start of study.
11. Increase in total SGOT, SGPT, BUN and creatinine by more than 3X ULN (upper limit of normal).
12. History of idiopathic or drug-induced agranulocytosis.
13. Substance-related disorders within 6 months prior to study start, borderline personality disorder, schizophrenia, or other major psychiatric disorders as defined by DSM-IV criteria.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Valproate & dextromethorphan 30 mg; Valproate and dextromethorphan 30 mg per day	Drug: Valproate; Drug: Dextromethorphan 30 mg; VPA & Dextromethorphan 30 mg per day
Experimental: VPA & dextromethorphan 60 mg; VPA & dextromethorphan 60 mg per day	Drug: Valproate; Drug: Dextromethorphan 60 mg per day; VPA plus dextromethorphan 60 mg per day
Active Comparator: VPA & Placebo; VPA & placebo	Drug: Valproate; Drug: Placebo; VPA plus placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Young's Mania Rating Scale (YMRS)	The severity of current manic symptoms will be assessed by using the YMRS	baseline, 1, 2, 4, 8 and 12 weeks
Hamilton Depression Rating Scale (HDRS)	The severity of depressive symptoms will be evaluated by HDRS	baseline, 1, 2, 4, 8 and 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
blood samples	The immune markers, cytokines will be measured at each time point to follow each patient's changes.	baseline, 1, 2, 4, 8 and 12 weeks
lipid profiles		baseline, after treatment

Collaborators and Investigators

• Sponsor: National Cheng-Kung University Hospital
• Collaborators: National Health Research Institutes, Taiwan; TTY Biopharm

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: August 23, 2010
• First Submitted That Met QC Criteria: August 23, 2010
• First Posted (Estimate): August 25, 2010

Study Record Updates

• Last Update Posted (Estimate): September 17, 2013
• Last Update Submitted That Met QC Criteria: September 16, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Bipolar and Related Disorders; Bipolar Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Tranquilizing Agents; Psychotropic Drugs; GABA Agents; Anticonvulsants; Antimanic Agents; Respiratory System Agents; Antitussive Agents; Valproic Acid; Dextromethorphan
• Other Study ID Numbers: HR-95-110