Clinical trial NCT01552837: Effects of Quetiapine on Ultrastructural Hippocampal and Neurochemical Changes in Patients With Bipolar Disorder: Searching for Antidepressant and Mood Stabilising Neurophysiology
Official title: Effects of Quetiapine on Ultrastructural Hippocampal and Neurochemical Changes in Patients With Bipolar Disorder: Searching for Antidepressant and Mood Stabilising Neurophysiology
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Bipolar Disorder
Keywords: Diffusion Tensor Imaging,
quetiapine
Bipolar Disorder
hippocampus
Volume Brain Morphometry
Magnetic Resonance Spectroscopy
effect of quetiapine on hippocampal neurogenesis
Lead sponsor: RWTH Aachen University
Sponsor class: OTHER
First posted: 2012-03-13
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Anisotropy in hippocampal formation detected with Diffusion Tensor Imaging (DTI)
timeFrame: after 6 weeks
Secondary outcomes:
measure: safety and tolerability of medical treatment
timeFrame: every time during the study
measure: Detection of pharmacologically induced localised volume changes
timeFrame: after 6 weeks
measure: Detection of pharmacologically induced localised changes in water content
timeFrame: after 6 weeks
measure: Detection of pharmacologically induced neurochemical changes in the medial temporal regions (Glx and NAA, choline)
timeFrame: after 6 weeks
measure: Detection of pharmacologically induced differential activation during an episodic memory task measured with fMRI.
timeFrame: after 6 weeks
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital Aachen
Study officials:
affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital Aachen
name: Klaus Mathiak, Prof MD
role: STUDY_DIRECTOR
References:
citation: 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. doi: 10.1006/jmrb.1994.1037.
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. doi: 10.1016/j.brainres.2005.09.043. Epub 2005 Nov 4.
citation: Vieta E. Mood stabilization in the treatment of bipolar disorder: focus on quetiapine. Hum Psychopharmacol. 2005 Jun;20(4):225-36. doi: 10.1002/hup.689.