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

RWTH Aachen University

Status

Completed

Conditions

Bipolar Disorder

Treatments

Drug: Seroquel

Study type

Interventional

Funder types

Other

Identifiers

NCT01552837

2007-000479-40 (EudraCT Number)

D1449L00030

EK 024/07 (Other Identifier)

07-010

Details and patient eligibility

About

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.

Full 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).

Enrollment

33 patients

Sex

All

Ages

18 to 55 years old

Volunteers

Accepts Healthy Volunteers

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