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

NCT01357967 | Unknown Phase 4

• 1 other identifier: Seroquel ISS D1443C00053
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• Change from baseline in HDRS scale

  -Hamilton Depression Rating Scale (HDRS) : Baseline, 1, 2, 4, 6 week

  0,1,2,4,6 weeks

Secondary Outcomes (1)

• Change from baseline in CGI, BDI, and YMRS scales

  0,1,2,4,6 weeks

Study Arms (2)

Seroquel XR adjunctive

EXPERIMENTAL

The 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).

Drug: Seroquel XR adjunctive

SSRI monotherapy

ACTIVE COMPARATOR

active comparator

Drug: SSRI monotherapy

Interventions

SSRI monotherapy DRUG

SSRI (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

Also known as: SSRI

SSRI monotherapy

Seroquel XR adjunctive DRUG

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

Also known as: Seroquel XR, quetiapine XR, quetiapine

Seroquel XR adjunctive

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Major depressive disorder (HRDS \> 18)
• N100 amplitude slope outlier (\< 0.21 or \> 1.59)
• Aged 18 to 55 years
• Provision of written informed consent prior to any study specific procedures

You may not qualify if:

• Pregnancy or lactation: : urine HCG (-)
• Patients who, in the opinion of the investigator, pose an imminent risk of suicide or a danger to self or others
• Known intolerance or lack of response to quetiapine fumarate and SSRI antidepressant, as judged by the investigator
• Hearing impairment
• 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
• 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
• Administration of a depot antipsychotic injection within one dosing interval (for the depot) before randomisation/baseline
• Substance or alcohol dependence at enrollment (except dependence in full remission, and except for caffeine or nicotine dependence), as defined by DSM-IV criteria
• Opiates, amphetamine, barbiturate, cocaine, cannabis, or hallucinogen abuse by DSM-IV criteria within 4 weeks prior to enrollment
• Medical conditions that would affect absorption, distribution, metabolism, or excretion of study treatment
• 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
• Involvement in the planning and conduct of the study
• Previous enrollment or randomisation of treatment in the present study.
• Participation in another drug trial within 4 weeks prior enrollment into this study or longer in accordance with local requirements
• A patient with Diabetes Mellitus (DM) fulfilling one of the following criteria

Sponsors & Collaborators

• Inje University: lead

Study Sites (2)

Psychiatry Department, Inje University Ilsan Paik Hospital

Goyang, Geyonggi, South Korea

RECRUITING

Inje University Ilsanpaik Hospital

Goyang-si, Gyeonggi-do, 411-706, South Korea

ACTIVE NOT RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Quetiapine Fumarate

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Dibenzothiazepines; Thiazepines; Thiepins; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Seung-Hwan Lee, MD, PhD

  Psychiatry Department Inje University Ilsan Paik Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jung In Kim, Mr

CONTACT

82-31-910-7776; p5p52@hanmail.net

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 19, 2011
• First Posted: May 23, 2011
• Study Start: May 1, 2011
• Primary Completion: December 1, 2012
• Study Completion: April 1, 2013
• Last Updated: November 1, 2012

Record last verified: 2012-10

Locations

KR (2)