Ziprasidone vs. Sertraline/Haloperidol in Psychotic Depression

• Sponsor: Duke University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00340379
• Collaborator: Pfizer (Industry), National Institute of Mental Health and Neuro Sciences, India (Other)
• Enrollment: 72
• Locations: 3
• Arms: 2
• Duration (Months): 28
• Patients Per Site: 24
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

The purpose of this study is to compare ziprasidone (Geodon) monotherapy for the treatment of psychotic major depression (PMD)with an antidepressant/antipsychotic combined therapy.

Condition or Disease	Intervention/Treatment	Phase
Affective Disorders	Drug: Ziprasidone; Drug: Sertraline; Drug: Haloperidol	Phase 2/Phase 3

Detailed Description

Psychotic depression is a well-established DSM-IV diagnostic subtype indicating the presence of hallucinations and/or delusions as part of the clinical presentation. Currently the treatment of choice for psychotic depression is either electroconvulsive therapy or combination of antipsychotic and antidepressant medications. Ziprasidone will be compared to standard of care treatment comprising a combination of an antidepressant, sertraline and an antipsychotic, haloperidol, over a 12-week period. An additional 12-week extension phase is also included for responders to the initial study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 72 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Comparison of Two Different Treatments for Major Depression With Psychotic Features: Ziprasidone vs. Combined Sertraline and Haloperidol
• Study Start Date: Apr 1, 2003
• Actual Primary Completion Date: Aug 1, 2005
• Actual Study Completion Date: Aug 1, 2005

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Ziprasidone Subjects in this arm received ziprasidone with a placebo to maintain the blind	Drug: Ziprasidone; Target dosage 120-160mg/day based on tolerance; Other Names: Geodon
Active Comparator: Sertraline/Haloperidol Subjects in this arm received a combination of sertraline and haloperidol with a placebo to maintain the blind. Sertraline dosage was 150-200mg/day and haloperidol was 6-8mg/day based on tolerance.	Drug: Sertraline; Target dosage 150-200mg/day based on tolerance.; Other Names: Zoloft ; Drug: Haloperidol; Target dosage 6-8mg/day based on tolerance.; Other Names: Haldol

Outcome Measures

Primary Outcome Measures

1. 21 Item Hamilton Depression Rating Scale [12 week]

   The scale rates 21 symptoms related to major depression. A total score of 0-7 is considered to be normal, scores of 20 or higher indicate moderately severe depression. Total scores range from a minimum of 0(not ill) to a maximum of 64 (severely ill).

2. Clinical Global Impression Improvement Scale [12 weeks]

   A 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. and rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. Overall the scale goes from a minimum of 1(very much improved) to a maximum of 7(very much worse).

3. Brief Psychiatric Rating Scale at 12 Weeks [12 weeks]

   A rating scale used to measure psychiatric symptoms such as depression, anxiety, hallucinations and unusual behaviour. Each symptom is rated 1-7 and in this version a total of 24 symptoms are scored. Thus the total range of scores is from a minimum of 24 to a maximum of 168. Lower scores are considered better, so the minimum total score of 24 indicates someone with no psychiatric symptoms, while any score over 40 is considered at least moderately severe, with only the most severely ill patients scoring over 60.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Males or females, aged 18-70 years

• If female, must state willingness to use medically accepted methods of birth control (if of reproductive age) and have negative pregnancy test

• Ability to understand study procedures and provide written informed consent

• A DSM-IV diagnosis of Major Depressive Disorder, with psychotic features, based on the Structured Clinical Interview for DSM-IV (SCID)

• Hamilton Depression Rating Scale score (21-item HDRS) greater than or equal to 22

Exclusion Criteria:

• A current or lifetime DSM-IV diagnosis of Bipolar Disorder, Schizophrenia or Schizoaffective Disorder

• A DSM-IV diagnosis of alcohol or substance abuse or dependence within 3 months of study entry

• A QTc greater than 460 msec or an abnormal EKG (except minor abnormalities considered by the site investigator to be clinically insignificant)

• A heart rate less than or equal to 50

• A personal or family history of QTc

• Any current or past history of syncope

• Concurrent treatment with medications associated with prolongation of the QTc

• Concurrent treatment with medications that may affect magnesium or potassium, such as diuretics

• Any acute, unstable or serious medical illness (eg, AIDS, history of seizures, history of CVAs).

• Baseline blood chemistries that are outside local reference ranges and which are felt clinically significant by the site investigator, or a potassium, magnesium or calcium level outside of local reference ranges or liver function tests that are greater than 20% above the upper limit of local reference ranges. If magnesium and/or potassium are below the lower limit of the local laboratory norm, they may be repeated and rechecked during the screening phase, and if within laboratory norms, the subjects may be included.

• History of unstable cardiovascular disease

• A significant risk of suicide in the judgement of the site investigator

• A history of allergy or hypersensitivity to haloperidol, sertraline or ziprasidone

• Any history of neuroleptic malignant syndrome

• Treatment with sertraline or ziprasidone within 30 days of study entry

• History of recent treatment with any long acting psychotropic medications

• Treatment with a MAO-inhibitor within 14 days of study entry

• Treatment with an investigational drug within 30 days of study entry

• Current use of carbamazepine, nefazodone, ketoconazole or erythromycin

• A positive pregnancy test

• A positive drug screen unless attributable to a prescribed medication (e.g. benzodiazepines)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Southern California	Los Angeles	California	United States	90033
2	Alexandria University	Alexandria		Egypt
3	National Institute of Mental Health and Neuroscience	Bangalore		India	560029

Sponsors and Collaborators

• Duke University
• Pfizer
• National Institute of Mental Health and Neuro Sciences, India

Investigators

• Principal Investigator: Frederick Cassidy, MD, Duke University
• Principal Investigator: George Simpson, MD, University of Southern California
• Principal Investigator: Ranga Krishnan, MD, Duke University
• Principal Investigator: Sumant Khanna, MD, National Institute of Mental Health and Neuroscience
• Principal Investigator: Adel Elsheshai, MD, Alexandria University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT00340379
• Other Study ID Numbers: Pro00008437; 3846-05-6R2
• First Posted: Jun 21, 2006
• Last Update Posted: Aug 19, 2014
• Last Verified: Feb 1, 2012

• Keywords provided by Duke University: Psychotic
• Additional relevant MeSH terms: Mental Disorders; Psychotic Disorders; Mood Disorders; Haloperidol; Haloperidol decanoate; Ziprasidone; Sertraline

Study Results

Participant Flow

Arm/Group Title	Ziprasidone	Sertraline/Haloperidol
Arm/Group Description	Target dosage of 120-160mg/day based on tolerance.	Target dosage of 150-200mg/day for sertraline and 6-8mg/day for haloperidol.
Period Title: Overall Study
STARTED	35	37
COMPLETED	27	28
NOT COMPLETED	8	9

Baseline Characteristics

Arm/Group Title	Ziprasidone	Sertraline/Haloperidol	Total
Arm/Group Description	Total of all reporting groups
Overall Participants	35	37	72
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	35 100%	37 100%	72 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	36.4 (8.7)	35.9 (12.0)	36.1 (10.5)
Sex: Female, Male (Count of Participants)
Female	21 60%	20 54.1%	41 56.9%
Male	14 40%	17 45.9%	31 43.1%
Region of Enrollment (participants) [Number]
Egypt	14 40%	15 40.5%	29 40.3%
United States	3 8.6%	5 13.5%	8 11.1%
India	18 51.4%	17 45.9%	35 48.6%

Outcome Measures

1. Primary Outcome

Title	21 Item Hamilton Depression Rating Scale
Description	The scale rates 21 symptoms related to major depression. A total score of 0-7 is considered to be normal, scores of 20 or higher indicate moderately severe depression. Total scores range from a minimum of 0(not ill) to a maximum of 64 (severely ill).
Time Frame	12 week

Outcome Measure Data

Analysis Population Description

Number of participants was ITT and imputed by LOCF

Arm/Group Title	Ziprasidone	Sertraline/Haloperidol
Arm/Group Description
Measure Participants	35	37
Mean (Standard Deviation) [Units on Hamilton Depression Scale]	13.6 (8.3)	11.0 (7.7)

2. Primary Outcome

Title	Clinical Global Impression Improvement Scale
Description	A 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. and rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. Overall the scale goes from a minimum of 1(very much improved) to a maximum of 7(very much worse).
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ziprasidone	Sertraline/Haloperidol
Arm/Group Description
Measure Participants	35	37
Mean (Standard Deviation) [units on a Clinical Impressions Scale]	3.1 (2.0)	2.5 (1.6)

3. Primary Outcome

Title	Brief Psychiatric Rating Scale at 12 Weeks
Description	A rating scale used to measure psychiatric symptoms such as depression, anxiety, hallucinations and unusual behaviour. Each symptom is rated 1-7 and in this version a total of 24 symptoms are scored. Thus the total range of scores is from a minimum of 24 to a maximum of 168. Lower scores are considered better, so the minimum total score of 24 indicates someone with no psychiatric symptoms, while any score over 40 is considered at least moderately severe, with only the most severely ill patients scoring over 60.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ziprasidone	Sertraline/Haloperidol
Arm/Group Description
Measure Participants	35	37
Mean (Standard Deviation) [units on a Psychiatric Rating scale]	28.7 (10.1)	25.8 (6.5)

Adverse Events

Arm/Group Title	Ziprasidone		Sertraline/Haloperidol
Arm/Group Description
All Cause Mortality
	Ziprasidone		Sertraline/Haloperidol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ziprasidone		Sertraline/Haloperidol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/35 (2.9%)		0/37 (0%)
General disorders
Death	1/35 (2.9%)	1	0/37 (0%)	0
Other (Not Including Serious) Adverse Events
	Ziprasidone		Sertraline/Haloperidol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	28/35 (80%)		33/37 (89.2%)
Gastrointestinal disorders
Gastritis	8/35 (22.9%)		2/37 (5.4%)
Nervous system disorders
Extrapyramidal symptoms	10/35 (28.6%)		15/37 (40.5%)
Akathisia	13/35 (37.1%)		8/37 (21.6%)
Tremors	4/35 (11.4%)		9/37 (24.3%)
Rigidity	4/35 (11.4%)		3/37 (8.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.