Schizophrenia
Conditions
Keywords
SSRI antidepressant, Negative symptoms, Schizophrenia
Brief summary
The aim of this double-blind, placebo-controlled trial is to establish the clinical and cost effectiveness of an SSRI antidepressant, citalopram, in the management of persistent negative symptoms of schizophrenia over a year.
Detailed description
The negative symptoms of schizophrenia represent an important dimension of psychopathology, and reflect the absence or diminution of normal behaviours and functions. They include deficiencies in emotional responsiveness, drive, and emotional and social engagement. Persistent negative symptoms are held to account for much of the long-term morbidity and poor functional outcome in patients with established schizophrenia, but if they prove resistant to antipsychotic medication there is a very limited evidence base regarding specific treatments. The aim of this double-blind, placebo-controlled trial is to establish the clinical and cost effectiveness of an SSRI antidepressant, citalopram, in the management of negative symptoms of schizophrenia over a year. The study sample will be adults with a diagnosis of schizophrenia, clinically stable for 3 months with a consistent antipsychotic regimen, and characterised by persistent negative symptoms to a criterion level of severity.
Interventions
DRUGPlacebo
Treatment with citalopram will be initiated at 20mg/day for the first 4 weeks (or one placebo capsule), followed by the option to increase the dose to 40mg per day (or two placebo capsules) for the remainder of the study period.
DRUGCitalopram
Treatment with citalopram will be initiated at 20mg/day for the first 4 weeks (or one placebo capsule), followed by the option to increase the dose to 40mg per day (or two placebo capsules) for the remainder of the study period.
Sponsors
University of Manchester
University of Southampton
King's College London
University of Oxford
University College, London
University of Bristol
Imperial College London
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 65 Years
Healthy volunteers
No
Inclusion criteria
* An OPCRIT (Operational Criteria Checklist for Psychosis: 57) diagnosis of schizophrenia, schizophreniform, schizoaffective disorder or psychosis NOS as defined by DSM-IV. * A negative subscale score of 20 or more on the Positive and Negative Syndrome Scale for Schizophrenia (PANSS). At least three of the seven items on the negative symptom subscale should be rated 3 or more. * Age 18-75 years, inclusive * Clinically stable for the last 3 months with a consistent antipsychotic regimen. * Competent and willing to provide written, informed consent.
Exclusion criteria
* Any medical contraindications to an SSRI antidepressant. * Currently receiving antidepressant or clinician wants to treat with an antidepressant; * Taking any medications that risk interacting with citalopram * Known congenital long QT syndrome, congestive heart failure, bradyarrhythmias * QT limit above the upper limit of normal as determined by an electrocardiogram (ECG) * Serum potassium and/or magnesium levels below the lower limits of normal * Currently fulfil criteria for major depressive disorder; alcohol/substance hazardous use or dependence in past 3 months * Treated with ECT in the last 8 weeks. * Pregnant or planning to become pregnant * Cognitive or language difficulties that would preclude subjects providing informed consent or compromise participation in study procedures. * Lack of consent, as judged by the patient's psychiatrist
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PANSS Negative Symptom Score | 12 weeks | The Positive and Negative Syndrome Scale (PANSS) is a semi-structured interview to elicit symptom ratings for 30 symptoms of psychosis, each scored between 1-7. The negative symptoms subscale uses the individual items in the PANSS that Marder identified as negative symptom (blunted affect, emotional withdrawal, poor rapport, passive/ apathetic social withdrawal, motor retardation, active social avoidance and lack of spontaneity/flow of conversation). Scores on these individual items are summed to create the subscale score. The subscale has a range of 7 to 49, with higher scores indicate greater psychopathology |
| Heinrich's Quality of Life Scale Score | 12 weeks | The Heinrichs Quality of Life scale is a 21-item scale based on a semi-structured interview designed to assess deficit symptoms. Each items is scored from 0-6 and the total score is the sum of all item responses. The total score has a range of 0 to 126, with higher scores indicating better functioning. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Citalopram Citalopram: 20mg/day for the first 4 weeks, followed by the option to increase the dose to 40mg per day for the remainder of the study period. | 30 |
| Placebo Placebo: one placebo capsule for the first 4 weeks, followed by the option to increase the dose to two placebo capsules for the remainder of the study period. | 32 |
| Total | 62 |
Baseline characteristics
| Characteristic | Citalopram | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 43.02 years STANDARD_DEVIATION 12.3 | 45.1 years STANDARD_DEVIATION 12.3 | 44.11 years STANDARD_DEVIATION 12.24 |
| Region of Enrollment United Kingdom | 30 participants | 32 participants | 62 participants |
| Sex: Female, Male Female | 4 Participants | 10 Participants | 14 Participants |
| Sex: Female, Male Male | 26 Participants | 22 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 32 |
| other Total, other adverse events | 8 / 30 | 11 / 32 |
| serious Total, serious adverse events | 0 / 30 | 0 / 32 |
Outcome results
Primary
Heinrich's Quality of Life Scale Score
The Heinrichs Quality of Life scale is a 21-item scale based on a semi-structured interview designed to assess deficit symptoms. Each items is scored from 0-6 and the total score is the sum of all item responses. The total score has a range of 0 to 126, with higher scores indicating better functioning.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Citalopram | Heinrich's Quality of Life Scale Score | 52 score on a scale | Standard Deviation 18.7 |
| Placebo | Heinrich's Quality of Life Scale Score | 49.5 score on a scale | Standard Deviation 20 |
p-value: 0.6895% CI: [-9, 14]Regression, Linear
Primary
PANSS Negative Symptom Score
The Positive and Negative Syndrome Scale (PANSS) is a semi-structured interview to elicit symptom ratings for 30 symptoms of psychosis, each scored between 1-7. The negative symptoms subscale uses the individual items in the PANSS that Marder identified as negative symptom (blunted affect, emotional withdrawal, poor rapport, passive/ apathetic social withdrawal, motor retardation, active social avoidance and lack of spontaneity/flow of conversation). Scores on these individual items are summed to create the subscale score. The subscale has a range of 7 to 49, with higher scores indicate greater psychopathology
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Citalopram | PANSS Negative Symptom Score | 21.5 units on a scale | Standard Deviation 5 |
| Placebo | PANSS Negative Symptom Score | 23 units on a scale | Standard Deviation 6.2 |
p-value: 0.3695% CI: [-4.91, 1.8]Regression, Linear