Add-on Dextromethorphan in Bipolar Disorders (DM)

National Cheng-Kung University

Status and phase: Completed; Phase 3

Conditions: Bipolar Disorder

Treatments: Drug: Valproate; Drug: Dextromethorphan 60 mg per day; Drug: Dextromethorphan 30 mg; Drug: Placebo

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01188265

HR-95-110

Details and patient eligibility

About

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.

Enrollment: 300 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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300 participants in 3 patient groups

Valproate & dextromethorphan 30 mg

Experimental group

Description:

Valproate and dextromethorphan 30 mg per day

Treatment:

Drug: Valproate

Drug: Dextromethorphan 30 mg

VPA & dextromethorphan 60 mg

Experimental group

Description:

VPA \& dextromethorphan 60 mg per day

Treatment:

Drug: Valproate

Drug: Dextromethorphan 60 mg per day

VPA & Placebo

Active Comparator group

Description:

VPA \& placebo

Treatment:

Drug: Placebo

Drug: Valproate