Benefits of Switching Antidepressants Following Early Nonresponse

NCT00519012 | Unknown Phase 4 DMC

• 1 other identifier: 19760629
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Introduction and Purpose: Most of the guidelines for the treatment of major depression recommend the use of antidepressants for 4 to 8 weeks. On the other hand, it has been recently reported that they start to show their antidepressant efficacy within a couple of weeks (1,2), contrary to the conventional theory. In addition, a good response (i.e. a 20% reduction in the Montgomery-Åsberg Depression Rating Scale \[MADRS\]) at week 2 is proposed to be a predictor of subsequent remission at week 6 (3,4), while nonresponse at week 2 could predict unfavourable outcome at week 8 (5). Furthermore, early worsening is suggested to be related to a low rate of remission at weeks 8 and 12(6).

Conditions

Depression

Keywords

early nonresponse

Outcome Measures

Primary Outcomes (1)

• The Montgomery-Asberg Depression Rating Scale

  at weeks1, 2, 3, 4, 6, 8, 12, 16, 20, 24 and 48 - 52.

Secondary Outcomes (1)

• The Clinical Global Impression 2. The Quick Inventory of Depressive Symptomatology self-reported

  at weeks1, 2, 3, 4, 6, 8, 12, 16, 20, 24 and 48 - 52.

Study Arms (2)

Arm-1

ACTIVE COMPARATOR

Sertraline to Paroxetine

Drug: Sertraline to Paroxetine

2

ACTIVE COMPARATOR

Paroxetine to Sertraline

Drug: Paroxetine to Sertraline

Interventions

Sertraline to Paroxetine DRUG

For subjects enrolled in this arm, sertraline will be initiated at 25mg, increased to 50mg on day 3, and maintained until day 14. If subjects show an early response (i.e. a 20% improvement in the MADRS total score from baseline) at week 2, sertraline will be continued and titrated at 50 - 100mg based on clinical judgment. On the other hand, if subjects fail to show an early response at week 2, they will be randomly divided into two groups. In one group, sertraline will be continued and titrated at 50 - 100mg, whereas in the other group sertraline will be switched to paroxetine. In this switching group, paroxetine will be started at 10mg on days 15 and 16, increased to 20mg on day 17, and further increased to 40mg by a weekly 10mg increase, while sertraline will be dosed at 25mg on day 15 and terminated on day 16.

Arm-1

Paroxetine to Sertraline DRUG

Paroxetine will be initiated at 10mg, increased to 20mg on day 3, and maintained until day 14. If subjects show an early response (i.e. a 20% improvement in the MADRS total score from baseline) at week 2, paroxetine will be continued and titrated at 20 - 40mg based on clinical judgment. On the other hand, if subjects fail to show an early response at week 2, they will be randomly divided into two groups. In one group, paroxetine will be continued and titrated at 20 - 40mg, whereas in the other group paroxetine will be switched to sertraline. In this switching group, sertraline will be started at 25mg on days 15 and 16, increased to 50mg on day 17, and further increased to 100mg by a weekly 25mg increase, while paroxetine will be dosed at 10mg on day 15 and terminated on day 16.

2

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Inpatients and outpatients who meet the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria of major depression disorder (MDD)
• Have not taken antidepressants for the previous one month
• Do not have emergent suicidal ideation defined as a score of 4 or less on suicidal thoughts item in the MADRS.

You may not qualify if:

• Unstable physical illness or clinically significant neurological disorder
• Having emergent suicidal idea defined as a score of 5 or more on the suicidal thoughts item in the MADRS.
• Having history of non-response or intolerance to paroxetine or sertraline.
• This study will be conducted with the approval of the Institutional Review Board of each participating hospital, and written informed consent will be obtained from all of the participants after providing a full explanation of the study.

Sponsors & Collaborators

• Oizumi Hospital: lead

Study Sites (1)

Oizumi Hospital

6-9-1 Oizumigakuen-cho, Nerima-ku, Tokyo, 178-061, Japan

RECRUITING

Related Publications (6)

• 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. doi: 10.1097/01.jcp.0000195042.62724.76.

  PMID: 16415707 BACKGROUND

• Taylor MJ, Freemantle N, Geddes JR, Bhagwagar Z. Early onset of selective serotonin reuptake inhibitor antidepressant action: systematic review and meta-analysis. Arch Gen Psychiatry. 2006 Nov;63(11):1217-23. doi: 10.1001/archpsyc.63.11.1217.

  PMID: 17088502 BACKGROUND

• Katz MM, Tekell JL, Bowden CL, Brannan S, Houston JP, Berman N, Frazer A. Onset and early behavioral effects of pharmacologically different antidepressants and placebo in depression. Neuropsychopharmacology. 2004 Mar;29(3):566-79. doi: 10.1038/sj.npp.1300341.

  PMID: 14627997 BACKGROUND

• Szegedi A, Muller MJ, Anghelescu I, Klawe C, Kohnen R, Benkert O. Early improvement under mirtazapine and paroxetine predicts later stable response and remission with high sensitivity in patients with major depression. J Clin Psychiatry. 2003 Apr;64(4):413-20. doi: 10.4088/jcp.v64n0410.

  PMID: 12716243 BACKGROUND

• Nierenberg AA, McLean NE, Alpert JE, Worthington JJ, Rosenbaum JF, Fava M. Early nonresponse to fluoxetine as a predictor of poor 8-week outcome. Am J Psychiatry. 1995 Oct;152(10):1500-3. doi: 10.1176/ajp.152.10.1500.

  PMID: 7573590 BACKGROUND

• Cusin C, Fava M, Amsterdam JD, Quitkin FM, Reimherr FW, Beasley CM Jr, Rosenbaum JF, Perlis RH. Early symptomatic worsening during treatment with fluoxetine in major depressive disorder: prevalence and implications. J Clin Psychiatry. 2007 Jan;68(1):52-7. doi: 10.4088/jcp.v68n0107.

  PMID: 17284130 BACKGROUND

MeSH Terms

Conditions

Depression

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Study Officials

• Shinichiro Nakajima, M.D.

  Oizumi Hospital

  STUDY CHAIR

Central Study Contacts

Shinichiro Nakajima, M.D.

CONTACT

008139242450; shinichiro_nakajima@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 20, 2007
• First Posted: August 21, 2007
• Study Start: August 1, 2007
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: September 28, 2009

Record last verified: 2009-09

Locations

JP (1)