Efficacy
The efficacy of SEROQUEL XR in the treatment of schizophrenia was demonstrated
in a short-term, 6-week, fixed-dose, placebo-controlled trial of inpatients and
outpatients with schizophrenia.1 SEROQUEL XR demonstrated
significant symptom improvement in PANSS (Positive and Negative Syndrome Scale)
Total Score as well as Positive and Negative Subscale Scores.2
PANSS Positive Subscale3:
• Hallucinatory behavior
• Delusions
• Conceptual disorganization
• Excitement
• Grandiosity
• Suspiciousness
• Hostility
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PANSS Negative Subscale3:
• Blunted affect
• Emotional withdrawal
• Poor rapport
• Passive/apathetic social withdrawal
• Difficulty in abstract thinking
• Lack of spontaneity/conversation
flow
• Stereotyped thinking
|
a Data from a single 6-week, randomized, double-blind,
placebo-controlled schizophrenia trial.
b P<0.05 vs placebo.
c P<0.001 vs placebo.
d Least squares means.
e Modified intention to treat.
f Last observation carried forward.
a Data from a single 6-week, randomized, double-blind,
placebo-controlled schizophrenia trial.
b The differences between treatment groups and placebo were
significant based on 95% confidence intervals.
c Least squares means.
d Modified intention to treat.
e Last observation carried forward.
In this same study, SEROQUEL XR demonstrated significant symptom improvement in
PANSS aggression/hostility and depression symptom cluster scores.2
PANSS Aggression/Hostility Symptom Cluster2:
• Excitement
• Hostility
• Uncooperativeness
• Poor impulse control
|
PANSS Depression
Symptom Cluster2:
• Somatic concern
• Anxiety
• Guilt feelings
• Depression
|
a Data from a single 6-week, randomized, double-blind,
placebo-controlled schizophrenia trial.
b The differences between treatment groups and placebo were
significant based on 95% confidence intervals.
c The PANSS aggression/hostility cluster includes symptoms of
excitement, hostility, uncooperativeness, and poor impulse control.2
d The PANSS depression symptom cluster includes symptoms of somatic
concern, anxiety, guilt feelings, and depression.2
e Least squares means.
f Modified intention to treat.
g Last observation carried forward.
The longer-term benefit of maintaining patients on monotherapy with SEROQUEL XR
after achieving a responder status for 16 weeks was demonstrated in a
controlled trial.1 Significantly more patients with schizophrenia were
relapse-free when maintained on SEROQUEL XR, vs placebo.4
a Postrandomized data from a 1-year, 2-phased, multicenter study of outpatients
with chronic schizophrenia.
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Phase 1 (16 weeks): open-label stabilization during
which patients were flexibly dosed with SEROQUEL XR between 400 and 800 mg/day.
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Phase 2 (up to 1 year): double-blind randomization during
which stabilized patients were continued on SEROQUEL XR (mean dose: 669 mg/day)
or switched to placebo.
Based on the results of a preplanned interim analysis, the study was terminated after the first
45 relapses. The analysis showed a significant difference between SEROQUEL XR and placebo groups.
-
84% reduction in risk relapse vs placebo4
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Hazard ratio: 0.16; P<0.0001. Number of patients who relapsed
was 9 (10.7%) for SEROQUEL XR vs 36 (41.4%) for placebo4
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During this trial, SEROQUEL XR maintained greater symptom control in patients with schizophrenia vs placebo
as demonstrated by PANSS Total Score (P<0.01) and Positive and Negative Subscale Scores (P<0.05)*4
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Safety findings of this longer-term trial were generally consistent with those of acute trials in schizophrenia1
*Number of patients with a score at randomization in at least one
post-randomization score, not including relapse, with SEROQUEL XR (n=94) vs
placebo (n=103) (total intent-to-treat population).
Dosing
SEROQUEL XR is indicated for the acute and maintenance treatment of schizophrenia. SEROQUEL is indicated for the treatment of depressive episodes in bipolar disorder; acute manic episodes in bipolar I disorder, as either monotherapy or adjunct therapy to lithium or divalproex; for the maintenance treatment of bipolar I disorder as adjunct therapy to lithium or divalproex; and schizophrenia. Patients should be periodically reassessed to determine the need for continued treatment and the appropriate dose.
Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk (1.6 to 1.7 times) of death, compared to placebo (4.5% vs 2.6%, respectively). SEROQUEL and SEROQUEL XR are not approved for the treatment of patients with dementia-related psychosis. (See Boxed Warning.)
Antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults in short-term studies of major depressive disorder and other psychiatric disorders. Patients of all ages started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. SEROQUEL and SEROQUEL XR are not approved for use in patients under the age of 18 years. SEROQUEL XR is not approved for the treatment of depression; however, SEROQUEL is approved for the treatment of bipolar depression. (See Boxed Warning.)
- Hyperglycemia, in some cases extreme and associated with ketoacidosis, hyperosmolar coma, or death, has been reported in patients treated with atypical antipsychotics, including quetiapine. The relationship of atypical use and glucose abnormalities is complicated by the possibility of increased risk of diabetes in the schizophrenic population and the increasing incidence of diabetes in the general population. However, epidemiological studies suggest an increased risk of treatment-emergent, hyperglycemia-related adverse reactions in patients treated with atypical antipsychotics. Patients starting treatment with atypical antipsychotics who have or are at risk for diabetes should undergo fasting blood glucose testing at the beginning of and periodically during treatment. Patients who develop symptoms of hyperglycemia should also undergo fasting blood glucose testing
- A potentially fatal symptom complex, sometimes referred to as Neuroleptic Malignant Syndrome (NMS), has been reported in association with administration of antipsychotic drugs, including quetiapine. Rare cases of NMS have been reported with quetiapine. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. The management of NMS should include immediate discontinuation of antipsychotic drugs
- Leukopenia, neutropenia, and agranulocytosis (including fatal cases), have been reported temporally related to atypical antipsychotics, including quetiapine. Patients with a pre-existing low white blood cell (WBC) count or a history of drug induced leukopenia/neutropenia should have their complete blood count monitored frequently during the first few months of therapy. In these patients, SEROQUEL and SEROQUEL XR should be discontinued at the first sign of a decline in WBC absent other causative factors. Patients with neutropenia should be carefully monitored, and SEROQUEL and SEROQUEL XR should be discontinued in any patient if the absolute neutrophil count is <1000/mm3
- Tardive dyskinesia (TD), a potentially irreversible syndrome of involuntary dyskinetic movements, may develop in patients treated with antipsychotic drugs. The risk of developing TD and the likelihood that it will become irreversible are believed to increase as the duration of treatment and total cumulative dose of antipsychotic drugs administered to the patient increase. TD may remit, partially or completely, if antipsychotic treatment is withdrawn. Quetiapine should be prescribed in a manner that is most likely to minimize the occurrence of TD
- Warnings and Precautions also include the risk of orthostatic hypotension, cataracts, seizures, hyperlipidemia, and possibility of suicide attempts. Examination of the lens by methods adequate to detect cataract formation, such as slit lamp exam or other appropriately sensitive methods, is recommended at initiation of treatment or shortly thereafter, and at 6-month intervals during chronic treatment. The possibility of a suicide attempt is inherent in schizophrenia, and close supervision of high risk patients should accompany drug therapy
- The most commonly observed adverse reactions associated with the use of SEROQUEL XR versus placebo in clinical trials for schizophrenia and bipolar disorder somnolence (25-52% vs. 10-13%), dry mouth (12-37% vs. 1-7%), constipation (6-10% vs. 3-6%), dyspepsia (5-7% vs. 1-4%), dizziness (10-13% vs. 4-11%), orthostatic hypotension (7% vs. 5%), weight gain (7% vs. 1%), increased appetite (12% vs. 6%), fatigue (6-7% vs. 2-4%), dysarthria (5% vs. 0%), and nasal congestion (5% vs. 1%).
- In long-term clinical trials of quetiapine, hyperglycemia (fasting glucose ≥126 mg/dL) was observed in 10.7% of patients receiving quetiapine (mean exposure 213 days) vs 4.6% in patients receiving placebo (mean exposure 152 days)
Please see Prescribing Information for SEROQUEL and SEROQUEL XR, including Boxed Warnings.