Levomilnacipran ER vs. Adjunctive Quetiapine for Adults With Inadequate Relief With SSRIs in MDD
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Intervention: Levomilnacipran; Quetiapine
Intervention description: treating major depression. A flexible dose regime of levomilnacipran ER 20-120 mg/d mg per day starting at 20 mg/d on Days 1-2, increasing to 40 mg/d on Days 3-7 in week 1, then flexibly dosed between 40 mg/d -120 mg/d during weeks 2 through 8; Quetiapine will be started at 50 mg/d on Day 1-2, increasing to 150 mg/d on Days 3-7 in Week 1 and then flexibly dosed between 150-300 mg/d during Weeks 1 through 8 along with their current antidepressant.
Intervention MeSH terms: Milnacipran; Quetiapine Fumarate; Levomilnacipran
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 60.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      This study's primary objective is to compare the efficacy and tolerability of switching
      patients with inadequate relief on generic SSRIs to levomilnacipran versus adding a new
      treatment (quetiapine) to the participants' existing treatment with people diagnosed with
      depression (major depression disorder).

      The secondary objective is to examine the response and remission rates following the switch
      from a generic SSRI to levomilnacipran ER and augmentation with quetiapine along with
      examining changes in neurocognitive and apathy measures after the switch.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age 18-65 years inclusive

          -  Current diagnosis of MDD based on DSM-IV criteria

          -  Able to understand study rules and procedures and willing to sign written informed
             consent for study participation

          -  Inadequate response to antidepressants: having a score of ≥14 on the 17-item Hamilton
             Anxiety Scale (HAMD) and not having a ≥ 50% reduction in HAMD or CGI-S scores from
             baseline after a retrospective confirmation of an adequate trial of a single
             antidepressant (defined as a minimum 6-week trial of acceptable therapeutic dose
             (daily dose ≥ 40 mg of fluoxetine, 40 mg of paroxetine, 20 mg of citalopram, 10 mg of
             escitalopram, 37.5 mg of paroxetine CR, 150 mg of sertraline, 100 mg of fluvoxamine).

          -  If female, nonpregnant/nonlactating status

          -  Duration of current MDD ≥ 4 weeks and < 24 months

          -  Not more than 2 treatment failures of adequate antidepressant trials for current
             episode of MDD

        Exclusion Criteria:

          -  Has previously participated in a levomilnacipran ER or quetiapine XR or quetiapine
             clinical study in previous 12 months

        Has 1 or more the following:

          -  Current or past history of: manic or hypomanic episode, schizophrenia or any other
             psychotic disorder defined in the DSM- 5

          -  Diagnosis of alcohol or other substance use disorder (except nicotine and caffeine) as
             defined in the DSM-5 that has not been in sustained full remission for at least 6
             months prior to screening (participant must also have negative urine drug screen prior
             to baseline).

          -  Presence or history of a clinically significant neurological disorder (including
             epilepsy)

          -  Poorly controlled Hypertension or Diabetes

          -  uncontrolled narrow-angle glaucoma

          -  hypersensitivity to levomilnacipran, milnacipran , quetiapine or quetiapine XR

          -  Neurodegenerative disorder.

          -  Has a thyroid stimulating hormone value outside the normal range at the Screening
             Visit that is deemed clinically significant by the investigator.

          -  Has clinically significant abnormal vital signs as determined by the investigator.

          -  Has a clinical significant abnormal electrocardiogram.

          -  Has screening laboratory values greater than 2.5 times the upper or lower limits of
             normal range or judged to be clinically significant

          -  Has a disease or takes medication that, in the opinion of the investigator, could
             interfere with the assessments of safety, tolerability, or efficacy or prevent the
             individual from completing the study.

          -  Female subjects of childbearing potential not on adequate contraception methods in the
             opinion of the investigator

             o If the female is childbearing, she must agree to use appropriate contraceptive
             measures for the duration of the study and for one month afterwards. Medically
             acceptable contraceptives include: (1) surgical sterilization (such as tubal ligation
             of hysterectomy), (2) approved hormonal contraceptives (such as birth control pills,
             patches, implants, or injections), (3) barrier methods (such as condom or diaphragm)
             used with a spermicide, or (4) an intrauterine device (IUD). Contraceptive measures
             such as Plan B ™, sold for emergency use after unprotected sex, are not acceptable
             methods for routine use. If the female does become pregnant during this study she must
             inform the study physician immediately.

          -  Has a significant risk of suicide according to Columbia Suicide Severity Rating Scale
             (CSSRS) or in the clinical judgment of the investigator

          -  History of suicide attempt in the previous 12 months

          -  MDD with postpartum onset, psychotic features or seasonal features

          -  Hamilton Anxiety Scale (HAM-A) baseline score ≥ 24

          -  Failure of ≥ 3 adequate trials of different antidepressants for the current episode of
             MDD

          -  ≥ 3 episodes major depression in previous 12 months or ≥ 8 lifetime episodes of MDD

          -  Current or previous use of an atypical or typical antipsychotic agent for augmentation
             of major depression or treatment of psychotic depression, mania psychosis, or
             agitation. Previous use of antipsychotics for insomnia will be permitted.