Clinical trial NCT01119430: Fluoxetine Versus Fluoxetine Plus DU125530 in Major Depressive Disorder
Official title: Fluoxetine Versus Fluoxetine Plus DU125530 in Latency of Antidepressant Response Shortening in Major Depressive Disorder
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Major Depression
Keywords: major depression
DU 125530
Treatment depression
Latency antidepressant
Lead sponsor: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Sponsor class: OTHER
First posted: 2010-05-07
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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

Eligibility criteria: 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.

Primary outcomes:
measure: Scores on Hamilton Depression Rating Scale
timeFrame: 8 time points through 8 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital de Sant Pau
Study officials:
affiliation: Psychiatrist, Hospital de Sant Pau
name: Victor Pérez, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Head of Departement, Psiquiatria, Hospital de Sant Pau
name: Enric Álvarez, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Psychiatrist, Hospital de Sant Pau
name: Dolors Puigdemont, MD
role: STUDY_CHAIR
affiliation: Psychiatrist, Hospital de Sant Pau
name: Josefina Pérez, MD
role: STUDY_DIRECTOR
References:
citation: 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.