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

Bipolar Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01552837
• Other study ID #: D1449L00030
• Secondary ID: 2007-000479-40EK
• Status: Completed
• Phase: N/A
• First received: March 2, 2012
• Last updated: March 9, 2012
• Start date: December 2007
• Est. completion date: December 2010

Study information

• Verified date: March 2012
• Source: RWTH Aachen University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: December 2010
• Est. primary completion date: February 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bipolar Disorder

Intervention

Drug:
• Seroquel
for 4 weeks, 300 - 800 mg per day in 2 doses

Locations

Country	Name	City	State
Germany	Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital Aachen	Aachen

Sponsors (1)

Lead Sponsor	Collaborator
RWTH Aachen University

Country where clinical trial is conducted

Germany, 

References & Publications (3)

Basser PJ, Mattiello J, LeBihan D. Estimation of the effective self-diffusion tensor from the NMR spin echo. J Magn Reson B. 1994 Mar;103(3):247-54. — View Citation

Luo C, Xu H, Li XM. Quetiapine reverses the suppression of hippocampal neurogenesis caused by repeated restraint stress. Brain Res. 2005 Nov 23;1063(1):32-9. Epub 2005 Nov 4. — View Citation

Vieta E. Mood stabilization in the treatment of bipolar disorder: focus on quetiapine. Hum Psychopharmacol. 2005 Jun;20(4):225-36. Review. Erratum in: Hum Psychopharmacol. 2005 Jul;20(5):375. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Anisotropy in hippocampal formation detected with Diffusion Tensor Imaging (DTI)	Detection of pharmacologically induced equivalents of neurogenesis and synaptic sprouting in the hippocampal region.	after 6 weeks	No
Secondary	safety and tolerability of medical treatment	Observation of adverse events and tolerability assessed by vital signs and clinical chemistry	every time during the study	Yes
Secondary	Detection of pharmacologically induced localised volume changes	Measurement with 3D MPRAGE (structural scan)	after 6 weeks	No
Secondary	Detection of pharmacologically induced localised changes in water content	differentiation between neurogenesis/sprouting and mere water intake	after 6 weeks	No
Secondary	Detection of pharmacologically induced neurochemical changes in the medial temporal regions (Glx and NAA, choline)	Measurement of glutamate and N-acetylaspartate in the medial temporal lobe with MRS	after 6 weeks	No
Secondary	Detection of pharmacologically induced differential activation during an episodic memory task measured with fMRI.	Measurement of BOLD response using fMRI during an episodic memory test	after 6 weeks	No