Clinical trial NCT00297947: High Dose of Quetiapine in Treating Subjects With Treatment Refractory Schizophrenia or Schizoaffective Disorder
Official title: A Randomized, Double-Blind, Parallel-Group, Fixed Dose, Clinical Trial of Quetiapine 600 mg/Day vs 1200 mg/Day for Patients With Treatment-Resistant Schizophrenia or Schizoaffective Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Schizophrenia
Schizoaffective Disorder
Keywords: schizophrenia
quetiapine
schizoaffective disorder
Lead sponsor: Manhattan Psychiatric Center
Sponsor class: OTHER
Collaborators: name: Nathan Kline Institute for Psychiatric Research
First posted: 2006-03-01
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will investigate the safety and efficacy of quetiapine in sub-optimally responding patients with DSM-IV schizophrenia using a double blind, randomized 12-week trial comparing oral doses of 1200 mg/d to 600 mg/d of quetiapine.

Detailed description: The study will be conducted at two sites: Manhattan Psychiatric Center (MPC), and the Clinical Research and Evaluation Facility at the Nathan S. Kline Institute for Psychiatric Research/Rockland Psychiatric Center (NKI). A total of 60 patients will be enrolled, 30 at each location. After a screening period of 1 week, all patients will be entering an open label, four-week quetiapine treatment period (run-in phase), during which quetiapine will be titrated to 600 mg PO daily and other adjunctive antipsychotics will be gradually tapered and discontinued. Other concomitant medications such as mood stabilizers will be maintained, if their dose has been stable for the preceding 2 months. Patients not responding to quetiapine treatment at 600 mg PO (defined as reduction of \< 15% change in Positive and Negative Syndrome Scale (PANSS) total score between start of run-in to end of week 4) during the run-in phase, will be eligible to enter the double blind phase. Study baseline will be Day 7 of Week 4 of the run-in phase. Patients qualifying for the double-blind phase will be randomly assigned to either high dose 1200 mg quetiapine daily (Group A) or to 600 mg quetiapine (Group B) daily and treated on the assigned dose in a double blind fashion for 8 weeks (Week 1 through Week 8 of double blind phase). Measures of extra-pyramidal side effects, psychopathology, and safety will be conducted throughout the trial.

Eligibility criteria: Inclusion Criteria:

1. DSM-IV criteria for chronic schizophrenia or schizoaffective disorder
2. Sub-optimal treatment-response
3. Total score \> 60 on the Positive and Negative Syndrome Scale (PANSS) at baseline of run-in phase and again at baseline of double blind phase
4. Age 18-64 years old
5. Signed informed consent
6. Patient is in good general medical health

Exclusion criteria:

1. History of failure to respond to 400 mg/day or more of clozapine for 8 contiguous weeks
2. History of failure to respond to quetiapine treatment at dosages \> 1200 mg daily for 6 contiguous weeks
3. History of quetiapine intolerance (e.g., clinically significant leukopenia or agranulocytosis, or severe dystonic reactions)
4. Significant recent history of violence or suicidal activity, which required \> 4 episodes of PRN anti-agitation medication per week
5. Mental retardation
6. Depot antipsychotic within 30 days before randomization
7. Significant medical illness requiring frequent dose adjustment or medication changes

Clozapine non-responders are explicitly excluded, as they would be unlikely to show a response in this study.

Primary outcomes:
measure: To see if mean extrapyramidal symptoms measure will change significantly from baseline to endpoint for the whole group and if the mean change in EPS measure is significantly different between quetiapine 1200mg daily group and quetiapine 600mg daily group
timeFrame: 8 weeks
Secondary outcomes:
measure: To see if treatment with quetiapine 1200 mg per day will improve total PANSS more robustly than quetiapine 600 mg per day
timeFrame: 8 weeks
Other outcomes:
Locations:
city: New York
country: United States
facility: Manhattan Psychiatric Center
state: New York
city: Orangeburg
country: United States
facility: Nathan Kline Institute for Psychiatric Research
state: New York
Study officials:
affiliation: Manhattan Psychiatric Center
name: Jean-Pierre Lindenmayer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Nathan Kline Institute for Psychiatric Research
name: Leslie Citrome, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Citrome L, Jaffe A, Levine J, Lindenmayer JP. Dosing of quetiapine in schizophrenia: how clinical practice differs from registration studies. J Clin Psychiatry. 2005 Dec;66(12):1512-6. doi: 10.4088/jcp.v66n1203.
citation: Lindenmayer JP, Citrome L, Khan A, Kaushik S, Kaushik S. A randomized, double-blind, parallel-group, fixed-dose, clinical trial of quetiapine at 600 versus 1200 mg/d for patients with treatment-resistant schizophrenia or schizoaffective disorder. J Clin Psychopharmacol. 2011 Apr;31(2):160-8. doi: 10.1097/JCP.0b013e31820f4fe0.