determining optimal treatment sequences in anxious depression (dots-ad)

Conditions: Anxious Depression; Depression

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.

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 criteria:
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.

Keywords: anxious depression