Fluoxetine Versus Fluoxetine Plus DU125530 in Major Depressive Disorder

Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Status and phase

Terminated

Phase 2

Conditions

Major Depression

Treatments

Drug: Placebo

Drug: DU125530

Study type

Interventional

Funder types

Other

Identifiers

NCT01119430

HSP-2003-01

Details and patient eligibility

About

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.

Full 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

Enrollment

50 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

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.