Depression, Major Depressive Disorder
Conditions
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
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.
Interventions
DRUGOxytocin
20 IU of intranasal oxytocin twice per day for 8 weeks, and a placebo (oral) for the 8 week trial
DRUGOxytocin and Tibolone
20 IU of intranasal oxytocin twice per day for 8 weeks, and 2.5mg oral tibolone for the 8 week trial
DRUGPlacebo
20 IU of intranasal placebo twice per day for 8 weeks, and a placebo (oral) for the 8 week trial
Sponsors
Monash University
The Alfred
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | 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
| Measure | Time frame |
|---|---|
| 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 |
| Change from baseline in Hamilton Rating Scale for Depression (HAM-D) | Assessed at different time points: 1 week, 2 weeks, 4 weeks, 8 weeks |
| 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 |
| Perceived stress scale | baseline, week 2, week 4, week 8 |
Countries
Australia
Contacts
Primary ContactCharlotte Keating, PhD
Outcome results
None listed