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

• Status: Unknown status
• Trial end date: 2013-04-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Inje University
• Treatments: Quetiapine Fumarate

Criteria

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