Clinical trial NCT01239888: Oxytocin and Tibolone Adjuncts in Treatment Resistant Depression - A Pilot Study
Official title: Phase IB Study of Efficacy and Safety of Oxytocin and Tibolone Adjuncts in Treatment Resistant Depression
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Depression
Major Depressive Disorder
Keywords: 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
Lead sponsor: The Alfred
Sponsor class: OTHER
Collaborators: name: Monash University
First posted: 2010-11-15
Enrollment: 15
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: Assessed at different time points: 1 week, 2 weeks, 4 weeks, 8 weeks
Secondary outcomes:
measure: Change from baseline in Hamilton Rating Scale for Depression (HAM-D)
timeFrame: Assessed at different time points: 1 week, 2 weeks, 4 weeks, 8 weeks
measure: Change from baseline in Beck Depression Inventory II (BDI-II)
timeFrame: Assessed at different time points: 1 week, 2 weeks, 4 weeks, 8 weeks
measure: Change from baseline in State Trait Anxiety Inventory (STAI)
timeFrame: Assessed at different time points: 1 week, 2 weeks, 4 weeks, 8 weeks
measure: Adverse Symptom Check List
timeFrame: baseline, week 2, week 4, week 8
measure: Perceived stress scale
timeFrame: baseline, week 2, week 4, week 8
measure: Pittsburgh sleep quality index
timeFrame: baseline, week 2, week 4, week 8
measure: Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF)
timeFrame: baseline, week 2, week 4, week 8
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Monash Alfred Psychiatry Research Centre
state: Victoria
Study officials:
affiliation: Monash University and the Alfred
name: Charlotte Keating, PhD
role: PRINCIPAL_INVESTIGATOR
References: