DepressionPhase 4NCT00519012
Benefits of Switching Antidepressants Following Early Nonresponse
A Phase 4 study testing Sertraline to Paroxetine and Paroxetine to Sertraline in people with Depression, run by Oizumi Hospital at 1 site in Japan.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Depression
- What is being tested?
- Sertraline to Paroxetine and Paroxetine to Sertraline
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteJapan
- Study dates
- Aug 2007to Dec 2010
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Japan1 site, 1 recruiting
- Recruiting
Oizumi Hospital
6-9-1 Oizumigakuen-cho, Nerima-ku, Tokyo, 178-061
Shinichiro Nakajima, M.D.
Shinichiro Nakajima, MD
About this study
Official title: Prospective 24-week Study, Comparing Clinical Outcomes Between Switching Antidepressants and Maintaining the Same Antidepressant in Patients With Major Depressive Disorder Who do Not Show a 20% Reduction in Symptoms at Week 2
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).
Read the detailed description
To the researchers' knowledge, there is no report to prospectively examine the benefits of switching antidepressants following early nonresponse. In this prospective 24-week study, the researchers will compare clinical outcomes between switching antidepressants and maintaining the same antidepressant in patients with major depressive disorder who do not show a 20% reduction in symptoms at week 2.
Materials and Methods: This open-label 24-week randomized controlled trial will be performed at psychiatric hospitals in Tokyo, Japan.
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 about the study.
In the short-term acute phase, sertraline will be initiated at 25 mg, increased to 50 mg on day 3, and maintained until day 14. If patients show an early response (i.e. ≧ 20% improvement in the MADRS total score from baseline), sertraline will be continued and titrated at 50 - 100 mg based on clinical judgment. On the other hand, if patients show no early response, they will be randomly divided into two groups. In one group, sertraline will be continued and titrated at 50 - 100 mg, whereas in the other group sertraline will be switched to paroxetine. Paroxetine will be started at 10 mg on days 15 and 16, increased to 20 mg on day 17, and further increased weekly by 10 mg from week 4 (i.e. day 22), while sertraline will be tapered by 25 mg each on days 15 and 16. In case patients are intolerant to adverse events, or they achieve remission (i.e. the MADRS total score ≦ 8), increasing the dose will be terminated. Lorazepam, lormetazepam, and mosapride will be allowed on a p.r.n. basis.
In the long-term follow-up phase after week 8, patients who achieve remission or response will be followed up and the same dose will be administered throughout. Assessments will include the MADRS, the clinical global impression scale (CGI), and the Quick Inventory of Depressive Symptomatology self-reported (QIDS-SR) (weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24). Adverse events will also be monitored on every visit.
- Conditions
- Depression
- Being tested
- Sertraline to Paroxetine, Paroxetine to Sertraline
- Keywords
- early nonresponse
- Medical subject headings
- Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sertraline to ParoxetineDrug
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.
Paroxetine to SertralineDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm-1 | Active comparator | Sertraline to Paroxetine Receives: Drug: Sertraline to Paroxetine |
| 2 | Active comparator | Paroxetine to Sertraline Receives: Drug: Paroxetine to Sertraline |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Montgomery-Asberg Depression Rating Scale
Measured: 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
Measured: at weeks1, 2, 3, 4, 6, 8, 12, 16, 20, 24 and 48 - 52.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2007 (estimated)
- Study startAug 2007
- Primary completionDec 2010 (estimated)
- Study completionDec 2010 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for DepressionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Oizumi Hospital
- Sponsor type
- University, hospital or other
- Investigators
- Shinichiro Nakajima, M.D., Study chair, Oizumi Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00519012
- Sponsor's protocol ID
- 19760629
- Status last verified
- Sep 2009
- First submitted
- 20 Aug 2007
- Last updated
- 28 Sep 2009
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 16415707Taylor 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.
PubMed 17088502Katz 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.
PubMed 14627997Szegedi 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.
PubMed 12716243Nierenberg 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.
PubMed 7573590Cusin 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.
PubMed 17284130
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective 24-week Study, Comparing Clinical Outcomes Between Switching Antidepressants and Maintaining the Same Antidepressant in Patients With Major Depressive Disorder Who do Not Show a 20% Reduction in Symptoms at Week 2
- ClinicalTrials.gov ID
- NCT00519012
- Acronym / sponsor ID
- 19760629
- Conditions
- Depression
- Keywords
- early nonresponse
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Oizumi HospitalUniversity, hospital or other
- Study start
- Aug 2007
- Primary completion
- Dec 2010 (estimated)
- Study completion
- Dec 2010 (estimated)
- First posted
- 21 Aug 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
To the researchers' knowledge, there is no report to prospectively examine the benefits of switching antidepressants following early nonresponse. In this prospective 24-week study, the researchers will compare clinical outcomes between switching antidepressants and maintaining the same antidepressant in patients with major depressive disorder who do not show a 20% reduction in symptoms at week 2.
Materials and Methods: This open-label 24-week randomized controlled trial will be performed at psychiatric hospitals in Tokyo, Japan.
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 about the study.
In the short-term acute phase, sertraline will be initiated at 25 mg, increased to 50 mg on day 3, and maintained until day 14. If patients show an early response (i.e. ≧ 20% improvement in the MADRS total score from baseline), sertraline will be continued and titrated at 50 - 100 mg based on clinical judgment. On the other hand, if patients show no early response, they will be randomly divided into two groups. In one group, sertraline will be continued and titrated at 50 - 100 mg, whereas in the other group sertraline will be switched to paroxetine. Paroxetine will be started at 10 mg on days 15 and 16, increased to 20 mg on day 17, and further increased weekly by 10 mg from week 4 (i.e. day 22), while sertraline will be tapered by 25 mg each on days 15 and 16. In case patients are intolerant to adverse events, or they achieve remission (i.e. the MADRS total score ≦ 8), increasing the dose will be terminated. Lorazepam, lormetazepam, and mosapride will be allowed on a p.r.n. basis.
In the long-term follow-up phase after week 8, patients who achieve remission or response will be followed up and the same dose will be administered throughout. Assessments will include the MADRS, the clinical global impression scale (CGI), and the Quick Inventory of Depressive Symptomatology self-reported (QIDS-SR) (weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24). Adverse events will also be monitored on every visit.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm-1 | Active comparator | Drug: Sertraline to ParoxetineSertraline to Paroxetine |
| 2 | Active comparator | Drug: Paroxetine to SertralineParoxetine to Sertraline |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sertraline to ParoxetineFor 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. | Drug | Arm-1 |
| Paroxetine to SertralineParoxetine 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. | Drug | 2 |
Primary outcome
The Montgomery-Asberg Depression Rating Scale
Time frame: at weeks1, 2, 3, 4, 6, 8, 12, 16, 20, 24 and 48 - 52.
1 secondary outcome
The Clinical Global Impression 2. The Quick Inventory of Depressive Symptomatology self-reported
Time frame: at weeks1, 2, 3, 4, 6, 8, 12, 16, 20, 24 and 48 - 52.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2009.
- Background: PubMed 16415707Papakostas 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.
- Background: PubMed 17088502Taylor 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.
- Background: PubMed 14627997Katz 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.
- Background: PubMed 12716243Szegedi 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.
- Background: PubMed 7573590Nierenberg 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.
- Background: PubMed 17284130Cusin 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shinichiro Nakajima, M.D. study chair
Oizumi Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Sertraline to Paroxetine and Paroxetine to Sertraline in people with Depression, run by Oizumi Hospital at 1 site in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Sep 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Shinichiro Nakajima, M.D. (008139242450, shinichiro_nakajima@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Montgomery-Asberg Depression Rating Scale (time frame: at weeks1, 2, 3, 4, 6, 8, 12, 16, 20, 24 and 48 - 52.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00519012, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2009.