Fluoxetine Versus Fluoxetine Plus DU125530 in Major Depressive Disorder

Fluoxetine Versus Fluoxetine Plus DU125530 in Latency of Antidepressant Response Shortening in Major Depressive Disorder

The purpose of this study is to examine whether the speed of the clinical antidepressant action of fluoxetine can be accelerated by administering DU125530 a full 5-HT1A antagonist.

Study Overview

• Status: Terminated
• Conditions: Major Depression
• Intervention / Treatment: Drug: Placebo; Drug: DU125530

Detailed Description

SSRI acts by blocking the serotonin transporter (5-HT), increasing the availability of serotonin at the synaptic cleft averting its reuptake. The increment of serotonin activates 5-HT1A presynaptic autoreceptors, resulting in a modulation in the release of serotonin by the presynaptic neuron. It is proposed that 5-HT1A receptor antagonism could accelerate the clinical effect of antidepressants by preventing this negative feedback.Preclinical data obtained with selective 5-HT1A antagonists, such as pindolol, and with mice lacking 5-HT1a receptors supports this hypothesis. Results on partial antagonists (pindolol) are conclusive in accelerating SSRI. It is reasonable to call into question whether a total antagonism of 5-HT1a receptors could imply a more rapid antidepressant response. To test this hypothesis we conducted a double blind, randomised, controlled trial with DU 123550 added to fluoxetine 20 mg/day

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08027
    • Hospital de Sant Pau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Consecutive eligible patients aged 18 to 70
• Diagnosis of unipolar major depression using DSM-IV criteria with moderate to severe symptoms (score e 18 on the Hamilton Depression Rating Scale-HDRS- of 17 items).
• There was a wash-out of 1 week of any antidepressant drug (specifically 28 days for fluoxetine) prior entering the study.
• Written informed consent was obtained from all participants.

Exclusion Criteria:

• Concurrent psychiatric disorders (DSM IV axis I, II cluster A or B)
• Failure to respond to drug treatment in current depressive episode
• Previous resistance to SSRIs or other antidepressant drug
• Suicide risk score e 3 on the HDRS.
• Participation in other drug trials within the previous month
• Presence of delusions or hallucinations
• History of substance abuse (including alcohol) in the past three months
• Pregnancy or lactation
• Organic brain disease or history of seizures
• Serious organic illnesses such as hypo or hyperthyroidism,cardiac arrhythmias, asthma, diabetes mellitus.
• Myocardial infarction in the past 6 month
• Frequent or severe allergic reactions
• Concomitant use of other psychotropic drugs (benzodiazepines were allowed), lockers or catecholamine-depleting agents
• Current structured psychotherapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Fluoxetine plus placebo	Drug: Placebo; Similar pill as active comparator twice a day; Other Names: Fluoxetine+placebo
Active Comparator: Fluoxetine plus DU125530	Drug: DU125530; 20mg/twice a day; Other Names: Fluoxetine+DU

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Scores on Hamilton Depression Rating Scale	8 time points through 8 weeks

Collaborators and Investigators

• Sponsor: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
• Investigators: Principal Investigator: Victor Pérez, MD, PhD, Psychiatrist, Hospital de Sant Pau; Principal Investigator: Enric Álvarez, MD, PhD, Head of Departement, Psiquiatria, Hospital de Sant Pau; Study Chair: Dolors Puigdemont, MD, Psychiatrist, Hospital de Sant Pau; Study Director: Josefina Pérez, MD, Psychiatrist, Hospital de Sant Pau

Publications and helpful links

General Publications

• Scorza MC, Llado-Pelfort L, Oller S, Cortes R, Puigdemont D, Portella MJ, Perez-Egea R, Alvarez E, Celada P, Perez V, Artigas F. Preclinical and clinical characterization of the selective 5-HT(1A) receptor antagonist DU-125530 for antidepressant treatment. Br J Pharmacol. 2012 Nov;167(5):1021-34. doi: 10.1111/j.1476-5381.2011.01770.x.

Study record dates

Study Major Dates

• Study Start: May 1, 2004
• Primary Completion (Actual): November 1, 2007
• Study Completion (Actual): November 1, 2007

Study Registration Dates

• First Submitted: May 6, 2010
• First Submitted That Met QC Criteria: May 6, 2010
• First Posted (Estimate): May 7, 2010

Study Record Updates

• Last Update Posted (Estimate): May 7, 2010
• Last Update Submitted That Met QC Criteria: May 6, 2010
• Last Verified: May 1, 2010

More Information

Terms related to this study

• Keywords: major depression; DU 125530; Treatment depression; Latency antidepressant
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Fluoxetine
• Other Study ID Numbers: HSP-2003-01