Overview
Acute, double-blind, adaptively randomized treatment with duloxetine or escitalopram, followed by double-blind, randomized adjunctive treatment with clonazepam or pregabalin for persistent symptoms.
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.
Eligibility
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:
- Surgical sterilization
- Oral contraceptives (e.g. estrogren-progestin combination or progestin)
- Transdermally-delivered contraceptives (e.g., Ortho-Evra), depot injections (e.g., Depo-Provera)
- Vaginal contraceptive ring (e.g., NuvaRing), contraceptive implants (e.g., Implanon, Norplant II/Jadelle)
- An intrauterine device
- 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.