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

NCT01282632 | Completed Phase 1 DMC

• 1 other identifier: ro123
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

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.

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; randomized

Outcome Measures

Primary Outcomes (18)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  day 43

Secondary Outcomes (2)

• Clinical Global Improvement Scale - Improvement

  day one

• Change from Baseline of Weight at 6 weeks

  day 43

Study Arms (2)

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.

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

Drug: Olanzapine

Interventions

Risperidone DRUG

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).

Risperidone

Olanzapine DRUG

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.

Olanzapine

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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;
• 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);
• \. Previous exposure to risperidone or olanzapine during the current episode.

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead

Study Sites (1)

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

MeSH Terms

Conditions

Depression; Depressive Disorder, Treatment-Resistant

Interventions

Risperidone; Olanzapine

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Anthony Levitt, MD

  Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

• Raymond Lam, MD

  University of British Columbia

  STUDY DIRECTOR

• Yves Chaput, MD

  University of Manitoba

  STUDY DIRECTOR

• Murray Enns, MD

  University of McGill

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 21, 2011
• First Posted: January 25, 2011
• Study Start: August 1, 2002
• Primary Completion: March 1, 2004
• Study Completion: March 1, 2004
• Last Updated: January 25, 2011

Record last verified: 2010-09

Locations

CA (1)