Integral Assessment in Unipolar Depression

Major Depressive Disorder Clinical Trial

— AIUNI  

Official title:

THE AIUNI - Integral Assessment in Unipolar Depression

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02268487
• Other study ID #: 795996
• Status: Recruiting
• Phase: Phase 4
• First received: October 8, 2014
• Last updated: December 10, 2015
• Start date: January 2014
• Est. completion date: January 2017

Study information

• Verified date: December 2015
• Source: University of Sao Paulo
• Contact: Fernando Fernandes, MD
• Phone: +55 11 997810107
• Email: fernandes2000[@]gmail.com
• Is FDA regulated: No
• Health authority: Brazil: National Committee of Ethics in Research
• Study type: Interventional

Clinical Trial Summary

The objective of this project is to assess the occurrence of early improvement within the first two weeks of antidepressant treatment and to correlate this improvement with favorable therapeutic outcome at the end of the acute and treatment continuation phases (8 and 24 weeks, respectively).

Description:

An ongoing debate, as long-running as treatment with antidepressants itself, is the delay in response to these drugs. Antidepressant drugs take 2 to 4 weeks to produce the treatment response effect (at least 50% improvement in depressive symptoms versus baseline levels). This delay in antidepressant response can prove highly problematic since, during this interim period, the patient is exposed to the suffering, debilitative effects, direct and indirect costs and risks associated with major depressive disorder (MDD).

Another important issue is when to define failure of a therapeutic trial and how to change treatment. Between 30 and 50% of MDD patients fail to respond to adequate first-line treatment. If favorable outcome is defined as full remission (as opposed to only 50% improvement) of the patient, the failure rate during first trial is greater still. Some reviews recommend dose adjustments every two weeks and a 4-8 week wait before treatment change for poor response. Despite these recommendations, the question over when and how to change treatment strategy warrants further debate.

Early improvement in antidepressant treatment is desirable because it reduces the suffering, losses and costs associated with MDD. In addition, the risk of suicidal ideation or committing suicide are reduced in patients presenting early improvement of depressive symptoms. However, early improvement not only reduces risk but also predicts outcome at the end of the acute phase of treatment. A number of studies investigating different antidepressants have shown that the presence of early response is a good predictor of favorable outcome at the end of the acute phase of treatment (after 6 or 8 weeks of treatment). A meta-analysis reviewing 41 simple or double-blind clinical trials included a total of 6562 patients.

Early improvement, defined as a 20% reduction in score on the Hamilton Depression Scale (HAMD-17) within 2 weeks, was associated with sustained response, remission (defined as HAM-D-17 score ≤7). While early response has been amply demonstrated in numerous clinical trials, there are gaps in knowledge on the subject. Scant studies have documented whether there are differences in the pattern of early improvement among different antidepressants. Similarly, there is a dearth of studies analyzing whether the presence or otherwise of early response has the same predictive value for different antidepressants. Another little explored aspect is the arbitrary nature of the criteria defining onset of improvement, early improvement, treatment response and symptomatological remission. Studies tend to reproduce previously-adopted criteria without elaborating on the exploratory analyses justifying the cut-off points adopted.

The aim of the present study is to assess the presence of early improvement after one and two weeks of treatment with sertraline. Besides assessing the presence of early response, the study will include an exploratory analysis assessing positive and negative predictive values, sensitivity and specificity of early improvement as a predictor of sustained response and remission after 6, 8 and 24 weeks of treatment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: January 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Patients Presenting Depressive Episode according to DSM-IV-TR

Exclusion Criteria:

• Patients presenting: psychotic symptoms, Axis 1 comorbidities (except specific phobia, specific social phobia and nicotine dependence) or risk of suicide (defined as score = 3 on item 3 of the 17-item HAMD or at the discretion of rater);

• Other exclusion criteria are having a serious or unstable medical condition, including cardiovascular, hepatic, endocrinologic, neurological or renal conditions.

• Clinically significant abnormalities on laboratory or ECG exams or those which, in the investigator ´s opinion, indicate a serious medical issue, require a major intervention or may interfere in the antidepressant treatment, also constitute grounds for exclusion.

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Drug:
• Sertraline
Treatment

Locations

Country	Name	City	State
Brazil	Insitute of Psychiatry of the University of São Paulo	São Paulo

Sponsors (1)

Lead Sponsor	Collaborator
University of Sao Paulo

Country where clinical trial is conducted

Brazil, 

References & Publications (3)

Papakostas GI, Perlis RH, Scalia MJ, Petersen TJ, Fava M. A meta-analysis of early sustained response rates between antidepressants and placebo for the treatment of major depressive disorder. J Clin Psychopharmacol. 2006 Feb;26(1):56-60. — View Citation

Szegedi A, Jansen WT, van Willigenburg AP, van der Meulen E, Stassen HH, Thase ME. Early improvement in the first 2 weeks as a predictor of treatment outcome in patients with major depressive disorder: a meta-analysis including 6562 patients. J Clin Psychiatry. 2009 Mar;70(3):344-53. Epub 2009 Feb 24. — View Citation

Thase ME. Methodology to measure onset of action. J Clin Psychiatry. 2001;62 Suppl 15:18-21. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Early Improvement	20% reduction of baseline score on the Hamilton Depression Scale (HAMD-17)	2 Weeks	Yes
Secondary	Response	50% reductions of baseline score on the Hamilton Depression Scale (HAMD-17)	4 and 8 weeks	Yes
Secondary	Remission	Score less than 7 points on the Hamilton Depression Scale (HAMD-17)	8 and 24 weeks	Yes