Official Title: “A Pilot Study of Treatment for Refractory Depression With Sequential Trials of Tranylcypromine, Tranylcypromine Plus Dextroamphetamine, Tranylcypromine Plus Triiodothyronine.”

This pilot study will assess the efficacy of several sequential pharmacological treatments for patients with Refractory Depression.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Crossover Assignment, Efficacy Study

Study Primary Completion Date: August 2006

This pilot study will recruit 40 patients with Major Depression and a history of at least two failed prior adequate somatic treatments. In addition to usual physical work-up, all patients will have extensive thyroid testing, and then will receive standard dose Tranylcypromine (i.e., max. 60 mg/d). Non-remitters will have dose increased to max. 120 mg/d if tolerated.

Non-remitters to high dose Tranylcypromine will then have Dextroamphetamine added with frequent blood pressure monitoring to max. 40 mg/d. Non-remitters will have Triiodothyronine added to the Tranylcypromine.

Intervention(s) in this Clinical Trial

• Drug: Tranylcypromine
  • standard dose:60 mg/d for a minimum of 8 weeks, a maximum of 17 weeks; high dose for non-remitters: up to 120 mg/day for a maximum of 9 weeks.
• Drug: Dextroamphetamine
  • up to 40 mg/day for 9 weeks, in combination with high dose of tranylcypromine for patients not remitting on the standard or high doses of tranylcypromine alone.
• Drug: Triiodothyronine
  • For patients not remitting on higher dose of tranylcypromine plus dextroamphetamine: Up to 75 mg/day for 8 weeks(+/- dextroamphetamine) (max 8 weeks) in combination with highest does of tranylcypromine (up to 120mg/day).

Primary Measures

• Hamilton Depression Scale (HAM-D)
  • Time Frame: up to 10 mos.
    Safety Issue?: No

Secondary Measures

• Beck Depression Inventory (BDI)
  • Time Frame: up to 10 mos.
    Safety Issue?: No
• Clinical Global Impression (CGI)
  • Time Frame: up to 10 mos.
    Safety Issue?: No
• Patient Global Impression (PGI)
  • Time Frame: up to 10 mos.
    Safety Issue?: No

Inclusion Criteria:

• Ages between 18-65
• Major Depression
• At least two prior ineffective antidepressant trials (at least 2 different mechanisms) or 1 inadequate ECT trial (at least 8 bilateral treatments)
• Physically healthy

Exclusion Criteria:

• Known Tranylcypromine allergy
• Unable to follow tyramine-free diet
• Known allergy, intolerance or prior addiction to any stimulant would preclude patient's inclusion in the Dextroamphetamine portion of the protocol
• Current substance use disorder including alcohol)(past six months); ever dependent on stimulants would preclude Dextroamphetamine portion of the protocol
• Unable or unwilling to discontinue antidepressants including OTC antidepressants such as St. John's Wort
• History of psychosis, such as schizophrenia or psychotic depression; history of bipolar mania will be allowed if on adequate mood stabilizer
• Suicidal ideation/activity that makes outpatient treatment unsafe, unless protocol can be conducted as inpatient
• Current systolic BP > 149 or diastolic BP > 89 mm Hg (two readings); adequately treated hypertension is acceptable
• Evidence of hypo- or hyperthyroidism
• Pregnancy, lactation, refusal to use adequate birth control

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: New York State Psychiatric Institute

Overall Clinical Trial Officials and Contacts

Jonathan W. Stewart, MD Principal Investigator New York State Psychiatric Institute - Columbia University Department of Psychiatry  

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00296686

Study ID Number: IRB4213

ClinicalTrials.gov Identifier: NCT00296686

Health Authority: United States: Institutional Review Board

Depression Evaluation Service - official website

New York State Psychiatric Institute - official website