Ziprasidone vs. Sertraline/Haloperidol in Psychotic Depression

A Comparison of Two Different Treatments for Major Depression With Psychotic Features: Ziprasidone vs. Combined Sertraline and Haloperidol

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.

Study Overview

• Status: Completed
• Conditions: Affective Disorders
• Intervention / Treatment: Drug: Ziprasidone; Drug: Sertraline; Drug: Haloperidol

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 Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Alexandria, Egypt
    • Alexandria University
• India
  • Bangalore, India, 560029
    • National Institute of Mental Health and Neuroscience
• United States
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
21 Item Hamilton Depression Rating Scale	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).	12 week
Clinical Global Impression Improvement Scale	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).	12 weeks
Brief Psychiatric Rating Scale at 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.	12 weeks

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: 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 record dates

Study Major Dates

• Study Start: April 1, 2003
• Primary Completion (Actual): August 1, 2005
• Study Completion (Actual): August 1, 2005

Study Registration Dates

• First Submitted: June 20, 2006
• First Submitted That Met QC Criteria: June 20, 2006
• First Posted (Estimate): June 21, 2006

Study Record Updates

• Last Update Posted (Estimate): August 19, 2014
• Last Update Submitted That Met QC Criteria: August 15, 2014
• Last Verified: February 1, 2012

More Information

Terms related to this study

• Keywords: Psychotic
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Psychotic Disorders; Mental Disorders; Mood Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Dopamine Agents; Serotonin Antagonists; Dopamine Antagonists; Anti-Dyskinesia Agents; Sertraline; Ziprasidone; Haloperidol; Haloperidol decanoate
• Other Study ID Numbers: Pro00008437; 3846-05-6R2 (Other Identifier: Duke legacy protocol number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No