RecruitingPhase 4NCT04245748

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

Sponsor

University of Cincinnati

Enrollment

84 participants

Start Date

Mar 1, 2020

Study Type

INTERVENTIONAL

Conditions

Depression Anxious 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.

Eligibility

Min Age: 18 YearsMax Age: 50 Years

Inclusion Criteria17

Written, informed consent.
Patients must be fluent in the English.
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 Criteria12

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.

Interventions

DRUGEscitalopram

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.

DRUGDuloxetine

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.