Determining Optimal Treatment Sequences in Anxious Depression (DOTS-AD)

Eligibility 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.
• * 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.