Schizophrenia
Conditions
Keywords
Electroconvulsive Therapy
Brief summary
This study will evaluate electroconvulsive therapy (ECT) in patients who have not responded adequately to clozapine.
Detailed description
ECT augmentation of clozapine will be compared to clozapine monotherapy in schizophrenic patients who continue to have psychotic symptoms despite optimal treatment with clozapine.
Interventions
PROCEDUREElectroconvulsive Therapy (ECT)
ECT will be used to augment clozapine in schizophrenic patients who continue to have psychotic symptoms despite optimal treatment with clozapine.
DRUGClozapine
Patients with psychotic symptoms will receive clozapine
Sponsors
National Institute of Mental Health (NIMH)
Northwell Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of schizophrenia according to DSM-IV criteria * Duration of illness 2 years or greater * Resistance to at least 2 antipsychotics * Clozapine resistance * Capacity to give informed consent * For women of childbearing capacity, a negative pregnancy test and patient agreement to use a medically accepted form of contraception * Brief Psychiatric Rating Scale score of at least a 4 on one of the four psychotic items on the psychotic sub-scale or a score of 12 on these 4 items combined. * Clinical Global Impressions (CGI) - severity rating of at least moderate (score of 4) * Receiving at least two 400 mg doses of chlorpromazine equivalents for at least 4 weeks (may include newer antipsychotics) * Having substantial psychotic symptoms despite at least 12 weeks of treatment (at least 8 weeks at a consistent dose)
Exclusion criteria
* schizoaffective disorder; bipolar disorder; * current affective episode; * Electroconvulsive Therapy (ECT) within the past 6 months * history of epilepsy; severe neurological or systemic disorder that could significantly affect cognition, behavior, or mental status (other than tardive dyskinesia or neuroleptic-induced parkinsonism); psychoactive substance dependence (other than nicotine or caffeine) within 1 month prior to entering the study * a score of less than 18 on the 24-item Hamilton Depression Rating Scale (HAM-D) * clinical determination that mood stabilizers were necessary and therefore could not be discontinued. * pregnancy. * affective disorders and prominent depressive symptoms because ECT is well known to be effective in those situations, and we wanted to avoid contamination of our results by improvement solely driven by the treatment of the affective symptoms.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rates in the ECT Plus Clozapine Group vs the Pharmacotherapy Group. | 8 Weeks | Response is defined as 40% reduction of symptoms in the psychotic symptom sub-scale (hallucinatory behavior, suspiciousness, conceptual disorganization, and unusual thought of content) of the Brief Psychiatric Rating Scale (BPRS) at the end of the 8-week study. BPRS assesses psychotic symptoms on a 18-item scale. The severity of each item is rated on a continuous scale from 1-7, with 1 being the least severe and 7 being most severe. Participants included in the study, at baseline had at least a moderate score of 4 on one of the four psychotic symptom sub-scale or a score of 12 on all four of these items combined (ranges 4 -28, with higher scores indicative of greater severity). A reduction of symptoms would be a sub-scale score which is 40% less than participants baseline score. If a participant enters the study with a sub-scale score of 15, to be considered a responder (at least a 40% reduction in symptoms score) his/her score must decrease by at least 6 points and be 9 or less. |
Countries
United States
Participant flow
Recruitment details
participants were recruited from the inpatient units of the Zucker Hillside Hospital at Glen Oaks, N.Y., and the Pilgrim State Psychiatric Center in Long Island, N.Y.
Pre-assignment details
In an 8-week random-assignment study incorporating nonblinded treatment and blinded assessments, patients with antipsychotic and clozapine-resistant schizophrenia were assigned to two treatment groups.
Participants by arm
| Arm | Count |
|---|---|
| Electroconvulsive Therapy With Medication Procedure/Surgery: Electroconvulsive Therapy (ECT) ECT will be used to augment clozapine in schizophrenic patients who continue to have psychotic symptoms despite optimal treatment with clozapine.
Drug: Clozapine Patients with psychotic symptoms will receive clozapine
Other Names:
• Clozaril | 20 |
| Medication Monotherapy Drug: Clozapine Patients with psychotic symptoms will receive clozapine
Other Names:
• Clozaril | 19 |
| Total | 39 |
Baseline characteristics
| Characteristic | Medication Monotherapy | Electroconvulsive Therapy With Medication | 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 | 19 Participants | 20 Participants | 39 Participants |
| Age, Continuous | 42.78 years STANDARD_DEVIATION 1.82 | 35.70 years STANDARD_DEVIATION 2.27 | 39.24 years STANDARD_DEVIATION 2.05 |
| Region of Enrollment United States | 19 participants | 20 participants | 39 participants |
| Sex: Female, Male Female | 13 Participants | 5 Participants | 18 Participants |
| Sex: Female, Male Male | 6 Participants | 15 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 20 | 0 / 19 |
| serious Total, serious adverse events | 0 / 20 | 0 / 19 |
Outcome results
Primary
Response Rates in the ECT Plus Clozapine Group vs the Pharmacotherapy Group.
Response is defined as 40% reduction of symptoms in the psychotic symptom sub-scale (hallucinatory behavior, suspiciousness, conceptual disorganization, and unusual thought of content) of the Brief Psychiatric Rating Scale (BPRS) at the end of the 8-week study. BPRS assesses psychotic symptoms on a 18-item scale. The severity of each item is rated on a continuous scale from 1-7, with 1 being the least severe and 7 being most severe. Participants included in the study, at baseline had at least a moderate score of 4 on one of the four psychotic symptom sub-scale or a score of 12 on all four of these items combined (ranges 4 -28, with higher scores indicative of greater severity). A reduction of symptoms would be a sub-scale score which is 40% less than participants baseline score. If a participant enters the study with a sub-scale score of 15, to be considered a responder (at least a 40% reduction in symptoms score) his/her score must decrease by at least 6 points and be 9 or less.
Time frame: 8 Weeks
Population: inpatient units of the Zucker Hillside Hospital at Glen Oaks, N.Y., and the Pilgrim State Psychiatric Center in Long Island, N.Y.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Electroconvulsive Therapy With Medication | Response Rates in the ECT Plus Clozapine Group vs the Pharmacotherapy Group. | 50 Percentage of responders |
| Medication Monotherapy | Response Rates in the ECT Plus Clozapine Group vs the Pharmacotherapy Group. | 0 Percentage of responders |