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Major Depressive Disorder | The Effect of Quetiapine XR in Depressive Patients Showing Aberrant N100 Amplitude Slope

Major Depressive Disorder research study

What is the primary objective of this study?

Recently, there are increasing data about intensity dependent amplitude change (IDAP: N100 amplitude slope) of auditory evoked Event Related Potential (ERP) components for its role on surrogate marker of central serotonergic activity. A high N100 amplitude slope reflects low serotonergic neurotransmission and vice versa. There are a couple of studies reporting associations of N1 amplitude slope with response to Citalopram (positive correlation) and Reboxetine (negative correlation) treatment in major depressive disorder patients (2,3). The investigator also published a case series about SSRI super-sensitivity and SSRI induced mania in patients with aberrantly high N100 slope (4). And serotonin transporter gene polymorphism was studied for its role about pathophysiology of bipolar disorder (5, 6, 7). Serotonin promoter gene was known to have significant relationship with N100 amplitude slope (8). Furthermore previous study showed that N100 amplitude slope was well correlated with hypomanic and hyperthymic personality (9). Conclusively from above results, the investigator hypothesized that if depressive patients show aberrant high or low N100 amplitude slope (N100 response outliers), they will not response well to SSRI medication. They will response better to quetiapine XR adjunctive therapy. In this study, the investigator will confirm it by comparing treatment effect between SSRI monotherapy and quetiapine XR adjunctive in aberrant N100 responder. Hypothesis First visit depressive patients might have monopolar or bipolar depression. If depressive patients show aberrantly high or low N100 amplitude slope, they will not response to SSRI medication. Patients who have aberrantly high or low N100 amplitude slope will response better to quetiapine XR adjunctive therapy.

Who is eligible to participate?

Inclusion Criteria: For inclusion in the study patients must fulfill all of the following criteria: 1. Major depressive disorder (HRDS > 18) 2. N100 amplitude slope outlier (< 0.21 or > 1.59) 3. Aged 18 to 55 years 4. Provision of written informed consent prior to any study specific procedures Exclusion Criteria: Any of the following is regarded as a criterion for exclusion from the study: 1. Pregnancy or lactation: : urine HCG (-) 2. Any DSM-IV Axis I disorder not defined in the inclusion criteria 3. Patients who, in the opinion of the investigator, pose an imminent risk of suicide or a danger to self or others 4. Known intolerance or lack of response to quetiapine fumarate and SSRI antidepressant, as judged by the investigator 5. Hearing impairment 6. Use of any of the following cytochrome P450 3A4 inhibitors in the 14 days preceding enrollment including but not limited to: ketoconazole, itraconazole, fluconazole, erythromycin, clarithromycin, troleandomycin, indinavir, nelfinavir, ritonavir, fluvoxamine and saquinavir 7. Use of any of the following cytochrome P450 3A4 inducers in the 14 days preceding enrollment including but not limited to: phenytoin, carbamazepine, barbiturates, rifampin, St. John's Wort, and glucocorticoids 8. Administration of a depot antipsychotic injection within one dosing interval (for the depot) before randomisation/baseline 9. Substance or alcohol dependence at enrollment (except dependence in full remission, and except for caffeine or nicotine dependence), as defined by DSM-IV criteria 10. Opiates, amphetamine, barbiturate, cocaine, cannabis, or hallucinogen abuse by DSM-IV criteria within 4 weeks prior to enrollment 11. Medical conditions that would affect absorption, distribution, metabolism, or excretion of study treatment 12. Unstable or inadequately treated medical illness (e.g. congestive heart failure, angina pectoris, hypertension or clinically relevant abnormal laboratory values) as judged by the investigator 13. Involvement in the planning and conduct of the study 14. Previous enrollment or randomisation of treatment in the present study. 15. Participation in another drug trial within 4 weeks prior enrollment into this study or longer in accordance with local requirements 16. A patient with Diabetes Mellitus (DM) fulfilling one of the following criteria - Unstable DM defined as enrollment glycosylated hemoglobin (HbA1c) > 8.5% - Admitted to hospital for treatment of DM or DM related illness in past 12 weeks. - Not under physician care for DM - Physician responsible for patient's DM care has not indicated that patient's DM is controlled. - Physician responsible for patient's DM care has not approved patient's participation in the study - Has not been on the same dose of oral hypoglycaemic drug(s) and/or diet for the 4 weeks prior to randomisation. For thiazolidinediones (glitazones) this period should not be less than 8 Weeks. - Taking insulin whose daily dose on one occasion in the past 4 weeks has been more than 10% above or below their mean dose in the preceding 4 weeks Note: If a diabetic patient meets one of these criteria, the patient is to be excluded even if the treating physician believes that the patient is stable and can participate in the study. 17. An absolute neutrophil count (ANC) of <= 1.5 x 1,000,000,000 per liter

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?

Major Depressive Disorder

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Drug:SSRI monotherapySSRI (paxil CR, es-citalopram, fluoxetine, sertraline) start with (paxil CR 12.5mg, es-citalopram 10mg, fluoxetine 20mg, sertraline 50mg) for 1 week up to maximal dosage, flexible dosage, usually in the morning

Drug:Seroquel XR adjunctiveQuetiapine group: seroquel XR 50mg Day 1 --> 50mg Day 2 --> 150mg Day 3 --> 150mg Day 4 --> adjustment usually at hs but can be daytime

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

Seroquel XR adjunctiveThe quetiapine XR adjunct group will be titrated up to 300mg. Initial dosing will begin at 50mg on Day 1 and 2, increased to 150mg on Day 3 and 4. Further adjustments will be able to be made upwards or downwards within the recommended dose range of 50mg to 300mg depending upon the clinical response and tolerance of the patient. Seroquel XR will be administered daily in the evening. The dosage of SSRIs will be maintained as low (es-citalopram 5mg, paxil CR 6.25mg, fluoxetine 10mg, and sertraline 25mg).

SSRI monotherapyactive comparator

Study Status

Unknown status

Start Date: May 2011

Completed Date: April 2013

Phase: Phase 4

Type: Interventional

Design:

Primary Outcome: Change from baseline in HDRS scale

Secondary Outcome: Change from baseline in CGI, BDI, and YMRS scales

Study sponsors, principal investigator, and references

Principal Investigator: Seung-Hwan Lee, MD, PhD

Lead Sponsor: Inje University

Collaborator:

More information:https://clinicaltrials.gov/show/NCT01357967

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