A Randomized Trial Comparing Efficacy and Tolerability of Levomilnacipran Switch Versus Adjunctive Quetiapine in Major Depressive Disorder (MDD) With Inadequate Response to SSRIs
Overview
- Phase
- Phase 3
- Intervention
- Levomilnacipran
- Conditions
- Major Depressive Disorder
- Sponsor
- Duke University
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Changes of Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief 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.
Detailed Description
1. Study Design 1) An 8-week, randomized rater blinded parallel group, 2-arm trial 2) Trial duration - 9 weeks 3) Drug doses * Levomilnacipran ER; Switching to a flexible dose regime of levomilnacipran ER 40-120 mg/day after initial dose of 20mg. * Quetiapine XR; Adjunct a flexible dose regimen of quetiapine XR 150-300 mg/day after initial dose of 50mg. 2. Objective 1) To compare the efficacy and tolerability of switching to levomilnacipran ER (40-120 mg/d) versus augmentation with quetiapine XR 150-300 mg/day to the patients' existing treatment for patients with inadequate relief on generic SSRIs in patients with MDD. 2) To examine the response following the switch from generic SSRI to levomilnacipran ER and augmentation with quetiapine XR. 3) To examine changes in neurocognitive and apathy measures after switching from SSRI to levomilnacipran ER and after augmentation with quetiapine XR in MDD
Investigators
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.
Arms & Interventions
Levomilnacipran
Levomilnacipran ER is switched from SSRI.
Intervention: Levomilnacipran
Quetiapine
Quetiapine XR is added in addition to current SSRI.
Intervention: Quetiapine
Outcomes
Primary Outcomes
Changes of Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score
Time Frame: Baseline to Week 8
A ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. Total scores will range from 0 to 60. Higher scores indicate greater severity of depressive episodes.
Secondary Outcomes
- Response Rate(Week 8)
- Remission Rate(Week 8)
- Changes in Neurocognition by Changes in Scores on Reyes Verbal Learning Test(Baseline to Week 8)
- Changes in Neurocognition by Changes in Scores on Scores on Digit Symbol Substitution Test (DSST)(Baseline to Week 8)
- Changes in Sexual Dysfunction by Changes in Scores on Arizona Sexual Experience Scale (ASEX)(Baseline to Week 8)
- Changes of Anxiety Symptoms in Scores on Hamilton Anxiety Rating Scale (HAM-A)(Baseline to Week 8)
- Changes of Quality of Life in Scores on Sheehan Disability Scale (SDS) Total(Baseline to Week 8)
- Changes in Scores on Apathy Evaluation Scale (AES).(Baseline to Week 8)
- Number of Subjects With Global Improvement in Scores on Clinical Global Impression Scale- Severity (CGI-S)(Baseline to Week 8)
- Number of Subjects With General Improvement in Scores on Clinical Global Impression Scale- Improvement (CGI-I)(Baseline to Week 8)