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What is the Antidepressant Mechanism of Action of Quetiapine in Bipolar Depression?

NCT00817323 · Status: WITHDRAWN · Phase: PHASE3 · Type: INTERVENTIONAL

Last updated 2014-07-08

No results posted yet for this study

Summary

PURPOSE The purpose of this study is to elucidate whether quetiapine fumurate (Seroquel) exerts its antidepressant activity in bipolar disorder through altering either serotonergic or catecholinergic activity.

HYPOTHESIS By depleting either serotonin or catecholamines in successfully treated bipolar patients, relapse will be induced and reveal which neurotransmitters are effected when receiving normal treatment

JUSTIFICATION While the exact mechanism of action of the classical antidepressants is not fully understood, strong evidence implicating serotonin and noradrenalin to be necessary (albeit insufficient) for the resolution of depression comes from neurotransmitter depletion studies. This biological evidence for each of these two neurotransmitters come from study paradigms in which the neurotransmitter (or its precursor) are selectively and effectively depleted from patients who have responded to antidepressants which either work through enhancing serotonin (for example, SRI antidepressants) or catecholamines (such as secondary amine tricyclics, Reboxetine, etc.). It has been shown, and replicated, that patients that respond to serotonin enhancing drugs precipitously and dramatically relapse when given a diet (often in the form of a milkshake) which is void of tryptophan, the precursor of serotonin. This diet often contains other long-chain amino acids to prevent any residual tryptophan in the system from entering the CNS. These patients who have then relapsed on the tryptophan-free diet have their tryptophan repleted and their mood improves often over a very short time frame (for example, five hours). When this technique is performed on patients responding to catecholamine-enhancing drugs there is no significant clinical effect. A similar approach can be taken with patients who respond to noradrelanine-enhancing drugs. Specifically, their catecholamine stores can be depleted by using dietary tyrosine. This reduces the synthesis of catecholamines and dopamine thus depleting pre-synaptic noradrenaline. For patients who responded to noradrenaline-enhancing drugs, this results in a relapse in terms of depressive symptomatology. When this dietary tyrosine strategy is applied to serotonin responders, there is no significant clinical effect.

Conditions

Interventions

PROCEDURE

Dietary amino-acid depletion

See detailed description

Sponsors & Collaborators

  • AstraZeneca

    collaborator INDUSTRY

  • University of British Columbia

    lead OTHER

Principal Investigators

  • Alex Goumeniouk, Ph.D · University of British Columbia

Study Design

Allocation
RANDOMIZED
Purpose
DIAGNOSTIC
Masking
DOUBLE
Model
SINGLE_GROUP

Eligibility

Min Age
19 Years
Max Age
65 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2009-01-31
Primary Completion
2013-12-31
Completion
2013-12-31

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT00817323 on ClinicalTrials.gov