Affective Disorders
Conditions
Keywords
Psychotic
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.
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.
Interventions
DRUGZiprasidone
Target dosage 120-160mg/day based on tolerance
DRUGSertraline
Target dosage 150-200mg/day based on tolerance.
DRUGHaloperidol
Target dosage 6-8mg/day based on tolerance.
Sponsors
Pfizer
National Institute of Mental Health and Neuro Sciences, India
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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). |
| 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. |
Countries
Egypt, India, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ziprasidone | 35 |
| Sertraline/Haloperidol | 37 |
| Total | 72 |
Baseline characteristics
| Characteristic | Ziprasidone | Sertraline/Haloperidol | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 35 Participants | 37 Participants | 72 Participants |
| Age, Continuous | 36.4 years STANDARD_DEVIATION 8.7 | 35.9 years STANDARD_DEVIATION 12 | 36.1 years STANDARD_DEVIATION 10.5 |
| Region of Enrollment Egypt | 14 participants | 15 participants | 29 participants |
| Region of Enrollment India | 18 participants | 17 participants | 35 participants |
| Region of Enrollment United States | 3 participants | 5 participants | 8 participants |
| Sex: Female, Male Female | 21 Participants | 20 Participants | 41 Participants |
| Sex: Female, Male Male | 14 Participants | 17 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 28 / 35 | 33 / 37 |
| serious Total, serious adverse events | 1 / 35 | 0 / 37 |
Outcome results
Primary
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).
Time frame: 12 week
Population: Number of participants was ITT and imputed by LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ziprasidone | 21 Item Hamilton Depression Rating Scale | 13.6 Units on Hamilton Depression Scale | Standard Deviation 8.3 |
| Sertraline/Haloperidol | 21 Item Hamilton Depression Rating Scale | 11.0 Units on Hamilton Depression Scale | Standard Deviation 7.7 |
Primary
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.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ziprasidone | Brief Psychiatric Rating Scale at 12 Weeks | 28.7 units on a Psychiatric Rating scale | Standard Deviation 10.1 |
| Sertraline/Haloperidol | Brief Psychiatric Rating Scale at 12 Weeks | 25.8 units on a Psychiatric Rating scale | Standard Deviation 6.5 |
Primary
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).
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ziprasidone | Clinical Global Impression Improvement Scale | 3.1 units on a Clinical Impressions Scale | Standard Deviation 2 |
| Sertraline/Haloperidol | Clinical Global Impression Improvement Scale | 2.5 units on a Clinical Impressions Scale | Standard Deviation 1.6 |