Oxytocin and Tibolone Adjuncts in Treatment Resistant Depression - A Pilot Study

Study Overview
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Brief Summary
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The purpose of this study is to determine whether an oxytocin ad-on, or oxytocin and tibolone ad-on can induce a response to antidepressants in patients with treatment resistant depression.

Detailed Description
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We are examining the efficacy and safety of oxytocin or oxytocin and tibolone with an antidepressant (SSRIs) in treatment resistant depression in a double-blind randomized clinical trial. A secondary objective is the evaluation of neurobiological factors contributing to drug efficacy in treatment resistant depression.

Official Title
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Phase IB Study of Efficacy and Safety of Oxytocin and Tibolone Adjuncts in Treatment Resistant Depression

Conditions
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Depression, Major Depressive Disorder

Intervention / Treatment
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* Drug: Oxytocin
* Drug: Oxytocin and Tibolone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women 18-45 years Current DSM-IV diagnosis of Major Depression Comorbid anxiety disorders secondary to depression will be included Past history of at least 2 failed treatment responses (including SSRIs) at the highest tolerated dose for at least 4-6 weeks A MADRS score >20 at randomization Women on a stable dose of an SSRI (sertraline, citalopram, escitalopram, paroxetine, fluoxetine or fluvoxamine) for at least 4-6 weeks. A negative pregnancy test at screening A clinically acceptable Pap smear within the past 2 years Must be able to use intranasal spray and swallow tablets Patients may take up to 2 sleep medications permitted at a dose considered reasonable by the investigating team. Limited adjustments in sleep medication are acceptable. Patients will be asked to notify the researchers of any changes to their sleep medication. Exclusion Criteria: Any previous history of adverse side-effects to escitalopram (or other SSRI) Use of oral contraceptives (or any hormonal method of contraception) for the duration of the study DSM-IV defined substance dependence, history of bipolar disorder, schizoaffective disorder or schizophrenia Significant unstable medical illness including epilepsy, diabetes or cardiac related, renal or liver disease, hormone dependent cancer or pregnancy A BMI<18 or > 34kg/m2 Planning for pregnancy Renal disease, history of cerebrovascular disease, thrombo-embolic disorders, myocardial infarction or angina at any time before study entry or thrombo-phlebitis within the last 5 years, or any other major illness that has occurred within the last 6 months. An undiagnosed genital bleeding Moderate to severe acne or hirsutism, have used antiandrogen therapy for acne or hirsutism in the preceding 5 years, have androgenic alopecia ( will exclude women with clinically meaningful androgen excess) Active malignancy, or treatment for malignancy in the preceding 6 months (excluding non-melanotic skin cancer) Alcohol consumption in excess of 3 standard drinks per day Lactose intolerance An abnormal thyroid stimulating hormone (TSH) value at screening confirmed by a Free T4 outside the normal laboratory range (patients with an abnormal TSH, normal Free T4 and no clinical signs or symptoms of thyroid disease, with or without replacement treatment, may be admitted to the study). A history of allergic reactions to androgens (oral or patch) Chronic medications: aspirin and warfarin

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Oxytocin<br> | Drug: Oxytocin<br>* 20 IU of intranasal oxytocin twice per day for 8 weeks, and a placebo (oral) for the 8 week trial<br>|
| Active Comparator: Oxytocin and Tibolone<br> | Drug: Oxytocin and Tibolone<br>* 20 IU of intranasal oxytocin twice per day for 8 weeks, and 2.5mg oral tibolone for the 8 week trial<br>* Other names: Livial (tibolone);|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* 20 IU of intranasal placebo twice per day for 8 weeks, and a placebo (oral) for the 8 week trial<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) |  | Assessed at different time points: 1 week, 2 weeks, 4 weeks, 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Hamilton Rating Scale for Depression (HAM-D) |  | Assessed at different time points: 1 week, 2 weeks, 4 weeks, 8 weeks | 
| Change from baseline in Beck Depression Inventory II (BDI-II) |  | Assessed at different time points: 1 week, 2 weeks, 4 weeks, 8 weeks | 
| Change from baseline in State Trait Anxiety Inventory (STAI) |  | Assessed at different time points: 1 week, 2 weeks, 4 weeks, 8 weeks | 
| Adverse Symptom Check List |  | baseline, week 2, week 4, week 8 | 
| Perceived stress scale |  | baseline, week 2, week 4, week 8 | 
| Pittsburgh sleep quality index |  | baseline, week 2, week 4, week 8 | 
| Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) |  | baseline, week 2, week 4, week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Depression, Treatment resistant depression, Oxytocin, Estrogen Modulators, HPA axis, Mental Disorders, Estrogens, Tibolone, Estrogen Receptor Modulators, Androgens, Hormones, Hormone Substitutes, Physiological Effects of Drugs, Pharmacologic Actions, Hormone Antagonists, Bone Density Conservation Agents, Estrogen Antagonists