Subjects Had Unipolar, Non-psychotic Major DepressionPhase 1/2NCT01282632

Risperidone vs. Olanzapine as add-on Treatment in Treatment Resistant Depression

A Phase 1/2 study testing Risperidone and Olanzapine in people with Subjects Had Unipolar, Non-psychotic Major Depression, run by Sunnybrook Health Sciences Centre at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Subjects Had Unipolar, Non-psychotic Major Depression
What is being tested?: Risperidone and Olanzapine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 42 participants
Where: 1 siteCanada
Study dates: Aug 2002to Mar 2004
Phase: Phase 1/2
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 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Subjects who meet all of the following criteria are eligible for this trial:
Male or female out-patients;
Aged between 18 and 65 years (extremes included);
Subjects suffering from a current episode of non-psychotic, unipolar depression as determined by the depression section of the SCID-IV.
Subjects with treatment resistant depression defined as failure to respond to two successive courses of monotherapy given in adequate doses for a minimum of 4 weeks with different antidepressants (the current course of antidepressant can be considered to second failed course) and;
Subjects currently taking a SSRI or a SNRI for at least 4 weeks, at adequate dosage and not responding, as defined by a score of 3 or more on the CGI-I. and no dose change for 2 weeks prior to entry.
A minimum score of 16 on the 17 item HAM-D
Ability to provide informed consent.

Who cannot join

Subjects meeting one or more of the following criteria cannot be selected:
Subjects who are actively suicidal as determined by a score of 3 on the suicide item on the HAM-D or in the opinion of the treating physician;
Other current (active symptomatology within the last 2 months) Axis I DSM IV diagnosis other than nicotine or caffeine dependence or other than an Anxiety disorder.
Use of disallowed concomitant therapy; or other psychotropic medication except occasional benzodiazepines. (See "Rescue Medication");
History of alcohol or drug abuse or dependence, within 3 months of entry into the trial);
Seizure disorder requiring medication;

Show all 14Show fewer

Active medical condition that requires urgent attention or that would contra-indicate the use of risperidone or olanzapine. For example stable thyroid disease or asthma would be acceptable, whereas acute hepatitis would not;
Participation in an investigational drug trial within 30 days prior to the start of the trial
Known sensitivity to risperidone, olanzapine or the antidepressant;
History of neuroleptic malignant syndrome (NMS);
Subjects who are at imminent risk of injury to self or others, or causing significant damage to property, as judged by the investigator;
Female subjects who are pregnant or breast-feeding;
Female subject of childbearing potential without adequate contraception (sterilization, barrier, IUD, oral contraceptives, intramuscular or subdermal administration of depot-progestagens);
15. Previous exposure to risperidone or olanzapine during the current episode.

Trial locations and contacts

1 site in 1 country.

Canada1 site

Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5

Other trials in Canada

About this study

Official title: A Double Blind Pilot Trial to Evaluate Efficacy Trends and Safety of Risperidone and Olanzapine as add-on Therapy to Serotonin Type Antidepressants in Subjects With Treatment Resistant Depression (TRD)

Atypical neuroleptics may have antidepressant qualities in bipolar depression and in unipolar depression. Some data support the use of both Risperidone and Olanzapine, but there are no direct comparisons of their relative efficacy and tolerability in treatment resistant depression. The current study was designed as a pilot study to examine efficacy and tolerability of Olanzapine vs. Risperidone add on to a failed serotonin re-uptake inhibitor (SSRI) in depression.

Read the detailed description

Overview of Study Design

This is a Canadian, multicentre, double blind, comparator trial in 42 patients with TRD. TRD is defined as the failure to respond adequately to two successive courses of different antidepressants at an adequate dose (at least fluoxetine 20 mg, citalopram 20 mg, paroxetine 20 mg, sertraline 100 mg, fluvoxamine 150 mg, venlafaxine 225 mg)) for at least 4 weeks. All subjects, at entry to the study will be currently not responding to treatment of at least 4 weeks duration of a serotonin re-uptake inhibitor (SSRI) or a selective nor-epinephrine and serotonin re-uptake inhibitor (SNRI). Non-response is defined as a score of 3 ("minimal improvement") or worse on the Clinical global Impression of Improvement .

The objective is to assess the appropriateness of the trial design and to determine sample size requirements for future controlled trials. In addition the efficacy and safety of oral doses of risperidone (.5-3 mg/day) and olanzapine (2.5-15 mg.day) as add-on therapy to any SSRI or SNRI in treatment resistant depression will be evaluated. Subjects meeting the screening criteria will enter a 6-week trial with risperidone or olanzapine added on to the current SSRI or SNRI therapy.

A medical/ psychiatric history, HAM-D-29 (only the first 17 items will be used for outcome), MADRS and HAM-A will be obtained at screening. At subsequent visits HAM-D, HAM-A, and MADRS will be performed and adverse events (spontaneous and using the CASES checklist) and concomitant medications will be collected.

Recruitment:

Subjects will drawn from two sources:

Outpatients currently attending the clinic at the sites. These subjects will already be in treatment or may have been referred from the local communities of the clinics involved in this study for consultation. Should these subjects drop out or once they have completed the study they will receive the treatment as usual at each site.
Advertisements. Advertisements will be placed in local media (radio, television, newspaper) identifying the nature of the study and providing a contact number. These advertisements will be approved by the local IRB's prior to posting.

Conditions: Subjects Had Unipolar, Non-psychotic Major Depression
Being tested: Risperidone, Olanzapine
Keywords: depression, treatment resistant depression, unipolar, non- psychotic major depression, add-on to a serotonin type antidepressants, risperidone, olanzapine, double blind comparison, randomized
Medical subject headings: Depression, Depressive Disorder, Treatment-Resistant

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

RisperidoneDrug
Risperidone will commence at 0.5 mg per day in a single daily dose given once in the evening. Clinicians will have the option, at each visit of increasing the risperidone dose to a maximum of 3 mg/day based on subject response and tolerability (please see Titration Recommendations below).
OlanzapineDrug
Olanzapine will commence at 2.5 mg per day in a single daily dose given once in the evening. Clinicians will have the option, at each visit, of increasing the olanzapine dose to a maximum of 15 mg/day based on subject response and tolerability.

Study groups in NCT01282632
Study group	Role	What they receive
Risperidone	Experimental	Commence at 0.5 mg once daily Increase, blindly, to 1 mg and then by 1 mg at discretion of clinicians through weeks 1-4 to a maximum of 3 mg. Receives: Drug: Risperidone
Olanzapine	Experimental	Commence at 2.5 mg once daily Increase to 5.0 mg, blindly, and then by 5 mg at the discretion of the clinician through weeks 1 - 4 to a maximum of 15 mg Receives: Drug: Olanzapine

What is being measured

The primary outcome is the main question the study is designed to answer.

Change from Baseline in Hamilton Depression Rating Scale at 1 week
Subject to be eligible for this trial must have a minimum score of 16 on the 17 item HAM-D which will be obtained at screening. Efficacy will be measured on the HAM-D 17 and defined as a 50% decrease from baseline to week 6.
Measured: day one
Change from Baseline in Montgomery Asberg Depression Scale (MADRS)at 1 week
MADRS will be obtained at screening. Efficacy will be measured by the MADRS and defined as a 50% decrease from baseline to week 6.
Measured: day one
Change from baseline Hamilton Rating Scale for Anxiety (HAM-A) at 1 week
Impact on anxiety will be measured by the HAM-A over the 6 weeks.
Measured: day one
Change from Baseline in Hamilton Depression Rating Scale at 2 weeks
Subject to be eligible for this trial must have a minimum score of 16 on the 17 item HAM-D which will be obtained at screening. Efficacy will be measured on the HAM-D 17 and defined as a 50% decrease from baseline to week 6.
Measured: day 8
Change from Baseline in Hamilton Depression Rating Scale at 3 weeks
Subject to be eligible for this trial must have a minimum score of 16 on the 17 item HAM-D which will be obtained at screening. Efficacy will be measured on the HAM-D 17 and defined as a 50% decrease from baseline to week 6.
Measured: day 15
Change from Baseline in Hamilton Depression Rating Scale at 4 weeks
Subject to be eligible for this trial must have a minimum score of 16 on the 17 item HAM-D which will be obtained at screening. Efficacy will be measured on the HAM-D 17 and defined as a 50% decrease from baseline to week 6.
Measured: day 22
Change from Baseline in Hamilton Depression Rating Scale at 5 weeks
Subject to be eligible for this trial must have a minimum score of 16 on the 17 item HAM-D which will be obtained at screening. Efficacy will be measured on the HAM-D 17 and defined as a 50% decrease from baseline to week 6.
Measured: day 29
Change from Baseline in Hamilton Depression Rating Scale at 6 weeks
Subject to be eligible for this trial must have a minimum score of 16 on the 17 item HAM-D which will be obtained at screening. Efficacy will be measured on the HAM-D 17 and defined as a 50% decrease from baseline to week 6.
Measured: day 43
Change from Baseline in Montgomery Asberg Depression Scale (MADRS)at 2 weeks
MADRS will be obtained at screening. Efficacy will be measured by the MADRS and defined as a 50% decrease from baseline to week 6.
Measured: day 8
Change from Baseline in Montgomery Asberg Depression Scale (MADRS)at 3 weeks
MADRS will be obtained at screening. Efficacy will be measured by the MADRS and defined as a 50% decrease from baseline to week 6.
Measured: day 15
Change from Baseline in Montgomery Asberg Depression Scale (MADRS)at 4 weeks
MADRS will be obtained at screening. Efficacy will be measured by the MADRS and defined as a 50% decrease from baseline to week 6.
Measured: day 22
Change from Baseline in Montgomery Asberg Depression Scale (MADRS)at 5 weeks
MADRS will be obtained at screening. Efficacy will be measured by the MADRS and defined as a 50% decrease from baseline to week 6.
Measured: day 29
Change from Baseline in Montgomery Asberg Depression Scale (MADRS)at 6 weeks
MADRS will be obtained at screening. Efficacy will be measured by the MADRS and defined as a 50% decrease from baseline to week 6.
Measured: day 43
Change from baseline Hamilton Rating Scale for Anxiety (HAM-A) at 2 weeks
Impact on anxiety will be measured by the HAM-A over the 6 weeks.
Measured: day 8
Change from baseline Hamilton Rating Scale for Anxiety (HAM-A) at 3 weeks
Impact on anxiety will be measured by the HAM-A over the 6 weeks.
Measured: day 15
Change from baseline Hamilton Rating Scale for Anxiety (HAM-A) at 4 weeks
Impact on anxiety will be measured by the HAM-A over the 6 weeks.
Measured: day 15
Change from baseline Hamilton Rating Scale for Anxiety (HAM-A) at 5 weeks
Impact on anxiety will be measured by the HAM-A over the 6 weeks.
Measured: day 22
Change from baseline Hamilton Rating Scale for Anxiety (HAM-A) at 6 weeks
Impact on anxiety will be measured by the HAM-A over the 6 weeks.
Measured: day 43

Secondary outcomes (2)

Clinical Global Improvement Scale - Improvement
Subjects currently taking a SSRI or a SNRI for at least 4 weeks, at adequate dosage and not responding, as defined by a score of 3 or more on the CGI-I.
Measured: day one
Change from Baseline of Weight at 6 weeks
Weight (Kg) will be measured with subjects at screening then at week 6.
Measured: day 43

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 2002Mar 2004

First posted25 Jan 2011 (estimated)
Study startAug 2002
Primary completionMar 2004
Study completionMar 2004

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Subjects Had Unipolar, Non-psychotic Major DepressionStudies of the same condition, open and under way.
More trials run by Sunnybrook Health Sciences CentreThe sponsor's other registered studies.
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 1/2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Single group
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 42 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01282632
Sponsor's protocol ID: ro123
Status last verified: Sep 2010
First submitted: 21 Jan 2011
Last updated: 25 Jan 2011
Results posted: No
Data monitoring committee: Yes

Study at a glance

From the registry record, last updated by the sponsor on 25 Jan 2011. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Double Blind Pilot Trial to Evaluate Efficacy Trends and Safety of Risperidone and Olanzapine as add-on Therapy to Serotonin Type Antidepressants in Subjects With Treatment Resistant Depression (TRD)
ClinicalTrials.gov ID: NCT01282632
Acronym / sponsor ID: ro123
Conditions: Subjects Had Unipolar, Non-psychotic Major Depression
Keywords: depression, treatment resistant depression, unipolar, non- psychotic major depression, add-on to a serotonin type antidepressants, risperidone, olanzapine, double blind comparison
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 42 participants (actual)
Lead sponsor: Sunnybrook Health Sciences CentreUniversity, hospital or other
Study start: Aug 2002
Primary completion: Mar 2004 (actual)
Study completion: Mar 2004 (actual)
First posted: 25 Jan 2011 (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.

Detailed description

Overview of Study Design

Recruitment:

Subjects will drawn from two sources:

Outpatients currently attending the clinic at the sites. These subjects will already be in treatment or may have been referred from the local communities of the clinics involved in this study for consultation. Should these subjects drop out or once they have completed the study they will receive the treatment as usual at each site.
Advertisements. Advertisements will be placed in local media (radio, television, newspaper) identifying the nature of the study and providing a contact number. These advertisements will be approved by the local IRB's prior to posting.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Single group
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Risperidone	Experimental	Drug: RisperidoneCommence at 0.5 mg once daily Increase, blindly, to 1 mg and then by 1 mg at discretion of clinicians through weeks 1-4 to a maximum of 3 mg.
Olanzapine	Experimental	Drug: OlanzapineCommence at 2.5 mg once daily Increase to 5.0 mg, blindly, and then by 5 mg at the discretion of the clinician through weeks 1 - 4 to a maximum of 15 mg

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

Male or female out-patients;
Aged between 18 and 65 years (extremes included);
Subjects suffering from a current episode of non-psychotic, unipolar depression as determined by the depression section of the SCID-IV.
Subjects with treatment resistant depression defined as failure to respond to two successive courses of monotherapy given in adequate doses for a minimum of 4 weeks with different antidepressants (the current course of antidepressant can be considered to second failed course) and;
Subjects currently taking a SSRI or a SNRI for at least 4 weeks, at adequate dosage and not responding, as defined by a score of 3 or more on the CGI-I. and no dose change for 2 weeks prior to entry.

Key exclusion criteria (14 listed)

Subjects who are actively suicidal as determined by a score of 3 on the suicide item on the HAM-D or in the opinion of the treating physician;
Other current (active symptomatology within the last 2 months) Axis I DSM IV diagnosis other than nicotine or caffeine dependence or other than an Anxiety disorder.
Use of disallowed concomitant therapy; or other psychotropic medication except occasional benzodiazepines. (See "Rescue Medication");
History of alcohol or drug abuse or dependence, within 3 months of entry into the trial);
Seizure disorder requiring medication;

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
RisperidoneRisperidone will commence at 0.5 mg per day in a single daily dose given once in the evening. Clinicians will have the option, at each visit of increasing the risperidone dose to a maximum of 3 mg/day based on subject response and tolerability (please see Titration Recommendations below).	Drug	Risperidone
OlanzapineOlanzapine will commence at 2.5 mg per day in a single daily dose given once in the evening. Clinicians will have the option, at each visit, of increasing the olanzapine dose to a maximum of 15 mg/day based on subject response and tolerability.	Drug	Olanzapine

Primary outcome

Change from Baseline in Hamilton Depression Rating Scale at 1 week
Time frame: day one
Subject to be eligible for this trial must have a minimum score of 16 on the 17 item HAM-D which will be obtained at screening. Efficacy will be measured on the HAM-D 17 and defined as a 50% decrease from baseline to week 6.
Change from Baseline in Montgomery Asberg Depression Scale (MADRS)at 1 week
Time frame: day one
MADRS will be obtained at screening. Efficacy will be measured by the MADRS and defined as a 50% decrease from baseline to week 6.
Change from baseline Hamilton Rating Scale for Anxiety (HAM-A) at 1 week
Time frame: day one
Impact on anxiety will be measured by the HAM-A over the 6 weeks.
Change from Baseline in Hamilton Depression Rating Scale at 2 weeks
Time frame: day 8
Subject to be eligible for this trial must have a minimum score of 16 on the 17 item HAM-D which will be obtained at screening. Efficacy will be measured on the HAM-D 17 and defined as a 50% decrease from baseline to week 6.
Change from Baseline in Hamilton Depression Rating Scale at 3 weeks
Time frame: day 15
Subject to be eligible for this trial must have a minimum score of 16 on the 17 item HAM-D which will be obtained at screening. Efficacy will be measured on the HAM-D 17 and defined as a 50% decrease from baseline to week 6.
Change from Baseline in Hamilton Depression Rating Scale at 4 weeks
Time frame: day 22
Subject to be eligible for this trial must have a minimum score of 16 on the 17 item HAM-D which will be obtained at screening. Efficacy will be measured on the HAM-D 17 and defined as a 50% decrease from baseline to week 6.
Change from Baseline in Hamilton Depression Rating Scale at 5 weeks
Time frame: day 29
Subject to be eligible for this trial must have a minimum score of 16 on the 17 item HAM-D which will be obtained at screening. Efficacy will be measured on the HAM-D 17 and defined as a 50% decrease from baseline to week 6.
Change from Baseline in Hamilton Depression Rating Scale at 6 weeks
Time frame: day 43
Subject to be eligible for this trial must have a minimum score of 16 on the 17 item HAM-D which will be obtained at screening. Efficacy will be measured on the HAM-D 17 and defined as a 50% decrease from baseline to week 6.
Change from Baseline in Montgomery Asberg Depression Scale (MADRS)at 2 weeks
Time frame: day 8
MADRS will be obtained at screening. Efficacy will be measured by the MADRS and defined as a 50% decrease from baseline to week 6.
Change from Baseline in Montgomery Asberg Depression Scale (MADRS)at 3 weeks
Time frame: day 15
MADRS will be obtained at screening. Efficacy will be measured by the MADRS and defined as a 50% decrease from baseline to week 6.
Change from Baseline in Montgomery Asberg Depression Scale (MADRS)at 4 weeks
Time frame: day 22
MADRS will be obtained at screening. Efficacy will be measured by the MADRS and defined as a 50% decrease from baseline to week 6.
Change from Baseline in Montgomery Asberg Depression Scale (MADRS)at 5 weeks
Time frame: day 29
MADRS will be obtained at screening. Efficacy will be measured by the MADRS and defined as a 50% decrease from baseline to week 6.
Change from Baseline in Montgomery Asberg Depression Scale (MADRS)at 6 weeks
Time frame: day 43
MADRS will be obtained at screening. Efficacy will be measured by the MADRS and defined as a 50% decrease from baseline to week 6.
Change from baseline Hamilton Rating Scale for Anxiety (HAM-A) at 2 weeks
Time frame: day 8
Impact on anxiety will be measured by the HAM-A over the 6 weeks.
Change from baseline Hamilton Rating Scale for Anxiety (HAM-A) at 3 weeks
Time frame: day 15
Impact on anxiety will be measured by the HAM-A over the 6 weeks.
Change from baseline Hamilton Rating Scale for Anxiety (HAM-A) at 4 weeks
Time frame: day 15
Impact on anxiety will be measured by the HAM-A over the 6 weeks.
Change from baseline Hamilton Rating Scale for Anxiety (HAM-A) at 5 weeks
Time frame: day 22
Impact on anxiety will be measured by the HAM-A over the 6 weeks.
Change from baseline Hamilton Rating Scale for Anxiety (HAM-A) at 6 weeks
Time frame: day 43
Impact on anxiety will be measured by the HAM-A over the 6 weeks.

2 secondary outcomes

Clinical Global Improvement Scale - Improvement
Time frame: day one
Change from Baseline of Weight at 6 weeks
Time frame: day 43

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Jan 2011.

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.

Anthony Levitt, MD principal investigator

Sunnybrook Health Sciences Centre

Raymond Lam, MD study director

University of British Columbia

Yves Chaput, MD study director

University of Manitoba

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Risperidone and Olanzapine in people with Subjects Had Unipolar, Non-psychotic Major Depression, run by Sunnybrook Health Sciences Centre at 1 site in Canada.

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 8 inclusion and 14 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: finished, as of the sponsor's last update on 25 Jan 2011. 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 Canada. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change from Baseline in Hamilton Depression Rating Scale at 1 week (time frame: day one). The study lists 18 primary outcomes in all. 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 NCT01282632.

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 25 Jan 2011.