Effects of Quetiapine on Ultrastructural Hippocampal and Neurochemical Changes in Patients With Bipolar Disorder: Searching for Antidepressant and Mood Stabilising Neurophysiology

Sponsor

RWTH Aachen University (Other)

Overall Status

Completed

CT.gov ID

NCT01552837

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The aim of the study was to determine the pharmacological induced equivalents of neurogenesis and synaptic sprouting in the hippocampus, localized volume changes, changes in water content and neurochemical changes in the medial temporal regions.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Disorder	Drug: Seroquel	N/A

Detailed Description

Quetiapine is an antipsychotic that has mood stabilizing and antidepressant effects (Vieta, 2005). Animal studies showed that the expression of neurotrophins and the subsequent modulation of the neuroplastic processes, including neurogenesis in the hippocampus, play a key role in the mechanism of mood stabilizing (Kim et al., 2004) and antidepressant (Santarelli et al., 2003). Since atypical antipsychotics also have antidepressant and mood stabilizing effect, it is hypothesized that the common mechanism of action in all three pharmacological classes is neurogenesis and synaptic sprouting in the hippocampal region. Thus, the aim of this study was to test this hypothesis.

Quetiapine was associated with antidepressant and mood stabilizing effects in patients with bipolar disorder (Vieta, 2005). The evidence based on animal studies shows that administration of quetiapine attenuates the decrease in levels of brain-derived neurotrophic factor in the hippocampi. This may explain the improved cognitive symptoms in patients with schizophrenia and depression (Luo et al., 2005, Park et al, 2006).

Study Design

Study Type:

Interventional

Actual Enrollment :

33 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Effects of Quetiapine on Ultrastructural Hippocampal and Neurochemical Changes in Patients With Bipolar Disorder: Searching for Antidepressant and Mood Stabilising Neurophysiology

Study Start Date :

Dec 1, 2007

Actual Primary Completion Date :

Feb 1, 2010

Actual Study Completion Date :

Dec 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Healthy volunteers MRI compatible, no present or past DSM-IV diagnosis
Active Comparator: patients with Bipolar Disorder MRI compatible, presence of DSM-IV diagnosis for Bipolar Disorder	Drug: Seroquel for 4 weeks, 300 - 800 mg per day in 2 doses

Arm

Intervention/Treatment

No Intervention: Healthy volunteers

MRI compatible, no present or past DSM-IV diagnosis

Active Comparator: patients with Bipolar Disorder

MRI compatible, presence of DSM-IV diagnosis for Bipolar Disorder

Drug: Seroquel

for 4 weeks, 300 - 800 mg per day in 2 doses

Outcome Measures

Primary Outcome Measures

Anisotropy in hippocampal formation detected with Diffusion Tensor Imaging (DTI) [after 6 weeks]
Detection of pharmacologically induced equivalents of neurogenesis and synaptic sprouting in the hippocampal region.

Secondary Outcome Measures

safety and tolerability of medical treatment [every time during the study]
Observation of adverse events and tolerability assessed by vital signs and clinical chemistry
Detection of pharmacologically induced localised volume changes [after 6 weeks]
Measurement with 3D MPRAGE (structural scan)
Detection of pharmacologically induced localised changes in water content [after 6 weeks]
differentiation between neurogenesis/sprouting and mere water intake
Detection of pharmacologically induced neurochemical changes in the medial temporal regions (Glx and NAA, choline) [after 6 weeks]
Measurement of glutamate and N-acetylaspartate in the medial temporal lobe with MRS
Detection of pharmacologically induced differential activation during an episodic memory task measured with fMRI. [after 6 weeks]
Measurement of BOLD response using fMRI during an episodic memory test

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

age ranging 18 - 55 years old
intelligence coefficient (IQ) of minimum 85 as estimated by MWT-B
MRI compatibility
for healthy volunteers - no DSM-IV diagnosis
patients should have had a diagnosis of bipolar disorder in accordance with DSM-IV.

Exclusion Criteria:

substances or alcohol abuse or dependence (except caffeine and nicotine) at enrollment;
medical conditions that would affect absorption, distribution, metabolism or excretion of study treatment;
unstable or inadequately treated medical illness (diabetes, angina, pectoris, hypertension);
diabetes mellitus
patients who in the opinion of the investigator pose a risk of suicide or danger to self or others,
patients who known intolerance or lack of response to Quetiapine fumarate,
patients who use of any of the cytochrome P450 3A4 inhibitors (ketoconazole, itraconazole, nelfinavir, ritonavir, fluvoxamine and saquinavir) in the 14 days preceding enrollment,
patients who use of any of the cytochrome P450 inducers (phenytoin, carbamazepine, barbiturates, rifampin, St. John's Wort and glucocorticoids) in the 14 days preceding enrollment,
current treatment of Quetiapine or use of mood stabilizer or antidepressant as co-medication throughout the study.
lack of inform consent