Suicide/suicidal thoughts or clinical worsening: Depression is associated with an increased risk of suicidal thoughts, self-harm and suicide (suicide-related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery. In addition, physicians should consider the potential risk of suicide-related events after abrupt cessation of quetiapine treatment, due to the known risk factors for the disease being treated.
Other psychiatric conditions for which quetiapine is prescribed can also be associated with an increased risk of suicide-related events. In addition, these conditions may be co-morbid with major depressive disorder. The same precautions observed when treating patients with major depressive disorder should therefore be observed when treating patients with other psychiatric disorders.
Patients with a history of suicide-related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment are known to be at greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment.
A meta analysis of placebo controlled clinical trials of antidepressant drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old.
Close supervision of patients and in particular those at high risk should accompany drug therapy especially in early treatment and following dose changes. Patients (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms present.
In shorter-term placebo controlled clinical studies of patients with major depressive episodes in bipolar disorder an increased risk of suicide-related events was observed in young adult patients (younger than 25 years of age) who were treated with quetiapine as compared to those treated with placebo (3.0% vs. 0%, respectively). In clinical studies of patients with MDD the incidence of suicide-related events observed in young adult patients (younger than 25 years of age) was 2.1% (3/144) for quetiapine and 1.3% (1/75) for placebo.
Neutropenia: Severe neutropenia (<0.5 x 109/L) has been uncommonly reported in quetiapine clinical trials. Most cases of severe neutropenia have occurred within the first two months of starting therapy with quetiapine. There was no apparent dose relationship. Possible risk factors for neutropenia include pre-existing low white cell count (WBC) and history of drug induced neutropenia. Quetiapine should be discontinued in patients with a neutrophil count <1 x 109/L. These patients should be observed for signs and symptoms of infection and neutrophil counts followed (until they exceed 1.5 x 109/L) (see Adverse Reactions).
Increases in blood glucose and hyperglycaemia: Increases in blood glucose and hyperglycaemia, and occasional reports of diabetes, have been observed in clinical trials with quetiapine. Although a causal relationship with diabetes has not been established, patients who are at risk for developing diabetes are advised to have appropriate clinical monitoring. Similarly, patients with existing diabetes should be monitored for possible exacerbation (see Adverse Reactions).
Lipids: Increases in triglycerides and cholesterol, and decreases in HDL have been observed in clinical trials with quetiapine (see Adverse Reactions). Lipid changes should be managed as clinically appropriate.
Pancreatitis: Pancreatitis has been reported in clinical trials and during the post marketing experience, however a causal relationship has not been established. Among the post marketing reports, many patients had factors which are known to be associated with pancreatitis such as increased triglycerides (see previous text), gallstones, and alcohol consumption.
Concomitant Illness: Seroquel XR should be used with caution in patients with known cardiovascular disease, cerebrovascular disease, or other conditions predisposing to hypotension. Quetiapine may induce orthostatic hypotension especially during the initial dose-titration period.
Dysphagia (see Adverse Reactions) and aspiration have been reported with Seroquel XR. Although a causal relationship with aspiration pneumonia has not been established, Seroquel XR should be used with caution in patients at risk for aspiration pneumonia.
Seizures: In controlled clinical trials, there was no difference in the incidence of seizures in patients treated with quetiapine or placebo. As with other antipsychotics, caution is recommended when treating patients with a history of seizures (see Adverse Reactions).
Tardive Dyskinesia and Extrapyrimidal Symptoms (EPS): Tardive dyskinesia is a syndrome of potentially irreversible, involuntary, dyskinetic movements that may develop in patients treated with antipsychotic drugs including quetiapine. If signs and symptoms of tardive dyskinesia appear, dose reduction or discontinuation of quetiapine should be considered. The symptoms of tardive dyskinesia can worsen or even arise after discontinuation of treatment (see Adverse Reactions).
In placebo-controlled clinical trials for schizophrenia and bipolar mania, the incidence of extrapyramidal symptoms was no different from that of placebo across the recommended therapeutic dose range. This predicts that quetiapine has less potential than typical antipsychotic agents to induce tardive dyskinesia in schizophrenia and bipolar mania patients. In short-term, placebo-controlled clinical trials for bipolar depression and major depressive disorder, the incidence of EPS was higher in quetiapine treated patients than in placebo treated patients (see Adverse Reactions).
Neuroleptic Malignant Syndrome: This has been associated with antipsychotic treatment including quetiapine (see Adverse Reactions). Clinical manifestations include hyperthermia, altered mental status, muscular rigidity, autonomic instability, and increased creatine phosphokinase. In such an event, Seroquel XR should be discontinued and appropriate medical treatment given.
QT Prolongation: In clinical trials quetiapine was not associated with a persistent increase in absolute QT intervals. However, in post marketing experience there were cases reported of QT prolongation with overdose (see Overdose). As with other antipsychotics, caution should be exercised when quetiapine is prescribed in patients with cardiovascular disease or family history of QT prolongation. Also caution should be exercised when quetiapine is prescribed either with medicines known to increase QT interval or with concomitant neuroleptics, especially for patients with increased risk of QT prolongation, i.e., the elderly, patients with congenital long QT syndrome, congestive heart failure, heart hypertrophy, hypokalemia, or hypomagnesemia (see Interactions).
Withdrawal: Acute withdrawal symptoms eg, insomnia, nausea, and vomiting have been described after abrupt cessation of antipsychotic drugs including quetiapine. Gradual withdrawal over a period of at least one to two weeks is advisable (see Adverse Reactions).
Effects on the ability to drive or operate machines: Given its primary CNS effects, quetiapine may interfere with activities requiring mental alertness. Therefore, patients should be advised not to drive or operate machinery, until individual susceptibility is known.
Use in Children: Children and adolescents (10 to 17 years of age): Although not all adverse reactions that have been identified in the adult patients have been observed in clinical trials with Seroquel in children and adolescent patients, the same special warnings and special precautions for use that appear above for adults should be considered for pediatrics. Additionally, changes in blood pressure and thyroid function tests and increases in weight and prolactin levels have been observed and should be managed as clinically appropriate. (See Adverse Reactions.)
Long-term safety data including growth, maturation, and behavioural development, beyond 26 weeks of treatment with Seroquel, is not available for children and adolescents (10 to 17 years of age).
Use in the Elderly: Elderly with dementia: Seroquel XR is not approved for the treatment of patients with dementia-related psychosis. In a meta-analysis of atypical antipsychotic drugs, it has been reported that elderly patients with dementia-related psychosis are at an increased risk of death compared to placebo. In two 10-week placebo-controlled quetiapine studies in the same patient population (n = 710; mean age: 83 years; range: 56-99 years) the incidence of mortality in quetiapine treated patients was 5.5% versus 3.2% in the placebo group. The patients in these trials died from a variety of causes that were consistent with expectations for this population. These data do not establish a causal relationship between quetiapine treatment and death in elderly patients with dementia.