Fluoxetine Versus Fluoxetine Plus DU125530 in Latency of Antidepressant Response Shortening in Major Depressive Disorder
Overview
- Phase
- Phase 2
- Intervention
- Placebo
- Conditions
- Major Depression
- Sponsor
- Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- Scores on Hamilton Depression Rating Scale
- Status
- Terminated
- Last Updated
- 15 years ago
Overview
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
Investigators
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.
Arms & Interventions
Fluoxetine plus placebo
Intervention: Placebo
Fluoxetine plus DU125530
Intervention: DU125530
Outcomes
Primary Outcomes
Scores on Hamilton Depression Rating Scale
Time Frame: 8 time points through 8 weeks