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
  • Phase

    Phase 2/Phase 3
  • Study Type

  • Study Participants

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.
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 Started
Apr 30
Primary Completion
Aug 31
Study Completion
Aug 31
Results Posted
Jun 04
Last Update
Aug 19

Drug Ziprasidone

Target dosage 120-160mg/day based on tolerance

  • Other names: Geodon

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

Ziprasidone Active Comparator

Subjects in this arm received ziprasidone with a placebo to maintain the blind

Sertraline/Haloperidol Active Comparator

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.


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)




All Events

Event Type Organ System Event Term Ziprasidone Sertraline/Haloperidol

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).


Units on Hamilton Depression Scale (Mean)
Standard Deviation: 8.3


Units on Hamilton Depression Scale (Mean)
Standard Deviation: 7.7

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).


units on a Clinical Impressions Scale (Mean)
Standard Deviation: 2.0


units on a Clinical Impressions Scale (Mean)
Standard Deviation: 1.6

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.


units on a Psychiatric Rating scale (Mean)
Standard Deviation: 10.1


units on a Psychiatric Rating scale (Mean)
Standard Deviation: 6.5



Age, Continuous

years (Mean)
Standard Deviation: 10.5

Age, Categorical

Region of Enrollment

Sex: Female, Male

Overall Study