Clinical trial NCT01188265: Add-on Dextromethorphan in Bipolar Disorders
Official title: Dextromethorphan Enhances the Therapeutic Efficacy of Valoproate in Bipolar Disorder Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bipolar Disorder
Lead sponsor: National Cheng-Kung University Hospital
Sponsor class: OTHER
Collaborators: name: National Health Research Institutes, Taiwan
name: TTY Biopharm
First posted: 2010-08-25
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Young's Mania Rating Scale (YMRS)
timeFrame: baseline, 1, 2, 4, 8 and 12 weeks
measure: Hamilton Depression Rating Scale (HDRS)
timeFrame: baseline, 1, 2, 4, 8 and 12 weeks
Secondary outcomes:
measure: blood samples
timeFrame: baseline, 1, 2, 4, 8 and 12 weeks
measure: lipid profiles
timeFrame: baseline, after treatment
Other outcomes:
Locations:
city: Tainan
country: Taiwan
facility: Ru-Band Lu
Study officials:
affiliation: National Cheng-Kung University Hospital
name: Ru-Band Lu, MD
role: PRINCIPAL_INVESTIGATOR
References: