Sequential Tranylcypromine (TC), TC + Dextroamphetamine and TC + Triiodothyronine for Refractory Depression

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

Detailed Description
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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.

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

Conditions
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Major Depression

Intervention / Treatment
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* Drug: Tranylcypromine
* Drug: Dextroamphetamine
* Drug: Triiodothyronine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tranylcypromine<br>sequential tranylcypromine (TC) followed by TC + dextroamphetamine followed by TC + T3 | Drug: Tranylcypromine<br>* 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.<br>* Other names: Parnate;Drug: Dextroamphetamine<br>* 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.<br>* Other names: Dexedrine;Drug: Triiodothyronine<br>* 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).<br>* Other names: Cytomel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton Depression Scale (HAM-D) |  | up to 10 mos. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Beck Depression Inventory (BDI) |  | up to 10 mos. | 
| Clinical Global Impression (CGI) |  | up to 10 mos. | 
| Patient Global Impression (PGI) |  | up to 10 mos. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Major Depression, Refractory Depression, Tranylcypromine, Dextroamphetamine, Triiodothyronine