Determining Optimal Treatment Sequences in Anxious Depression (DOTS-AD)
Purpose
Acute, double-blind, adaptively randomized treatment with duloxetine or escitalopram, followed by double-blind, randomized adjunctive treatment with clonazepam or pregabalin for persistent symptoms.
Conditions
- Anxious Depression
- Depression
Eligibility
- Eligible Ages
- Between 18 Years and 50 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Written, informed consent. - Patients must be fluent in the English. - 18 to 50 years of age, inclusive, at Visit 1. - Patients must meet DSM-5 criteria for generalized, social and/or separation anxiety disorder and/or panic disorder, confirmed by the MINI.99 Patients may also meet criteria for persistent depressive disorder or major depressive disorder however, these may not be the primary focus of treatment. - HAM-A score ≥20 at Visits 1 and 2. - Clinical Global Impressions- Severity (CGI-S) score ≥4 at Visits 1 and 2. - No clinically significant abnormalities on physical examination and EKG. - Negative pregnancy test at Visit 1 in females. - Negative urine drug screen at Visit 1. - Sexually active patients must practice a reliable method of contraception (Section 15.0) that will continue for the duration of the study and for a minimum of 30 days following the end of study participation. Reliable methods of contraception are defined below; other forms of contraceptives (pharmacological and/or non-pharmacological) are not accepted: 1. Surgical sterilization 2. Oral contraceptives (e.g. estrogren-progestin combination or progestin) 3. Transdermally-delivered contraceptives (e.g., Ortho-Evra), depot injections (e.g., Depo-Provera) 4. Vaginal contraceptive ring (e.g., NuvaRing), contraceptive implants (e.g., Implanon, Norplant II/Jadelle) 5. An intrauterine device 6. Diaphragm plus condom. - For patients directly enrolling into Phase 2: treatment with escitalopram (or its racemic equivalent citalopram) or duloxetine for ≥6 weeks, at time of screening.
Exclusion Criteria
- DSM-5 diagnosis other than generalized anxiety, social anxiety, separation anxiety or panic disorder(s) that is the primary focus of treatment. - A history of intellectual disability. - Suicide risk as determined by either: (1) any suicide attempt within the past 6 months and/or (2) significant risk at Visit 1 (Screening) or Visit 2 (Baseline), as judged by the Investigator. - Allergy, intolerance, non-response or hypersensitivity to escitalopram, duloxetine, pregabalin or clonazepam. - Subjects taking other medications that require a taper or washout of more than 5 days. - Patients who have initiated/terminated psychotherapy/behavior therapy within 1 month before Visit 2 (Baseline) will be excluded; if the patient is engaged in psychotherapy, it must have been stable for 1 month prior to baseline. - A clinically-significant medical illness. - QTc >450 in males or >460 in females (prolonged QTc based on American Heart Association recommendations for Standardization and Interpretation of the EKG100 - Alcohol or substance use disorder within 6 months of baseline (nicotine use is permitted). - Positive urine pregnancy test/pregnancy or breast feeding. - A positive urine drug screen. - Patients who are unable to swallow capsules.
Study Design
- Phase
- Phase 4
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Active Comparator Escitalopram |
Adaptively randomized, double-blind treatment with escitalopram for 11 weeks in Phase 1. Non-remitting patients will be randomized in Phase 2 to adjunctive clonazepam or pregabalin for 8 weeks. Additionally, adults who are already treated with escitalopram or citalopram for at least 6 weeks prior to screening, may enter Phase 2 and be randomized to adjunctive clonazepam or pregabalin for 8 weeks. |
|
|
Active Comparator Duloxetine |
Adaptively randomized, double-blind treatment with duloxetine for 11 weeks in Phase 1. Non-remitting patients will be randomized in Phase 2 to adjunctive clonazepam or pregabalin for 8 weeks. Additionally, adults who are already treated with duloxetine for at least 6 weeks prior to screening, may enter Phase 2 and be randomized to adjunctive clonazepam or pregabalin for 8 weeks. |
|
Recruiting Locations
More Details
- Status
- Recruiting
- Sponsor
- University of Cincinnati
Detailed Description
The study will consist of 2 phases (Figure 1). Eighty-four adults will be enrolled in Phase 1 and will be adaptively randomized (initially 1:1) to acute, double-blind treatment with escitalopram or duloxetine for 11 weeks. Remission status will be determined at week 10. Remitting patients (CGI-S ≤2) will resume treatment as usual, which may consist of outpatient referral. Non-remitting patients (CGI-S ≥3), will continue into Phase 2 and will be randomized to adjunctive clonazepam or pregabalin for 8 weeks. Twenty adults treated with escitalopram (or its racemic equivalent, citalopram) or duloxetine for ≥6 weeks (at screening) will be enrolled into Phase 2 and will be randomized to receive adjunctive clonazepam or pregabalin for 8 weeks.
