Determining Optimal Treatment Sequences in Anxious Depression (DOTS-AD)
Study Details
Study Description
Brief Summary
Acute, double-blind, adaptively randomized treatment with duloxetine or escitalopram, followed by double-blind, randomized adjunctive treatment with clonazepam or pregabalin for persistent symptoms.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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. |
Drug: Escitalopram
Escitalopram, a SSRI, commercially known as LexaproTM, is commonly prescribed for anxiety disorders and is FDA-approved for acute and maintenance treatment of MDD and GAD.
Other Names:
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| 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. |
Drug: Duloxetine
Duloxetine, a SNRI, commercially known as CymbaltaTM, is FDA-approved for the treatment of GAD, MDD, diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain in adults.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Change from Baseline in Hamilton Anxiety Rating Scale (HAM-A) total score [Week 2 to 20]
The HAM-A rating scale is a test of 14 items measuring the severity of anxiety symptoms. Each item is rated on a 5-point ordinal scale, ranging from 0 (not present) to 4 (severe). Total scores range from 0 to 56. A lower score is favorable.
- Change from Baseline in the Clinical Global Impression of Severity (CGI-S) [Week 2 to 20]
CGI-S is a seven point scale where 1=Normal and 7=Among the most extremely ill patients.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Written, informed consent.
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Patients must be fluent in the English.
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18 to 50 years of age, inclusive, at Visit 1.
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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.
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HAM-A score ≥20 at Visits 1 and 2.
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Clinical Global Impressions- Severity (CGI-S) score ≥4 at Visits 1 and 2.
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No clinically significant abnormalities on physical examination and EKG.
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Negative pregnancy test at Visit 1 in females.
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Negative urine drug screen at Visit 1.
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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:
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Surgical sterilization
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Oral contraceptives (e.g. estrogren-progestin combination or progestin)
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Transdermally-delivered contraceptives (e.g., Ortho-Evra), depot injections (e.g., Depo-Provera)
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Vaginal contraceptive ring (e.g., NuvaRing), contraceptive implants (e.g., Implanon, Norplant II/Jadelle)
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An intrauterine device
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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:
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DSM-5 diagnosis other than generalized anxiety, social anxiety, separation anxiety or panic disorder(s) that is the primary focus of treatment.
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A history of intellectual disability.
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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.
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Allergy, intolerance, non-response or hypersensitivity to escitalopram, duloxetine, pregabalin or clonazepam.
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Subjects taking other medications that require a taper or washout of more than 5 days.
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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.
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A clinically-significant medical illness.
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QTc >450 in males or >460 in females (prolonged QTc based on American Heart Association recommendations for Standardization and Interpretation of the EKG100
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Alcohol or substance use disorder within 6 months of baseline (nicotine use is permitted).
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Positive urine pregnancy test/pregnancy or breast feeding.
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A positive urine drug screen.
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Patients who are unable to swallow capsules.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Cincinnati, Department of Psychiatry & Behavioral Neuroscience | Cincinnati | Ohio | United States | 45219 |
Sponsors and Collaborators
- University of Cincinnati
Investigators
- Principal Investigator: Jeffrey Strawn, MD, FAACAP, University of Cincinnati
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Strawn DOTS-AD