The most commonly reported Adverse Drug Reactions (ADRs) with quetiapine are somnolence, dizziness, dry mouth, mild asthenia, constipation, tachycardia, orthostatic hypotension and dyspepsia.
As with other antipsychotics, weight gain, syncope, neuroleptic malignant syndrome, leucopenia, neutropenia and peripheral oedema, have been associated with quetiapine.
The incidences of ADRs associated with quetiapine therapy, are tabulated according to the format recommended by the Council for International Organizations of Medical Sciences (CIOMS III Working Group; 1995). (See Table 1.)
Click on icon to see table/diagram/image
Extrapyramidal symptoms: The following clinical trials (monotherapy and combination therapy) included treatment with Seroquel and Seroquel XR.
In short-term, placebo-controlled clinical trials in schizophrenia and bipolar mania the aggregated incidence of EPS was similar to placebo [schizophrenia: 7.8% for quetiapine and 8% for placebo; bipolar mania: 11.2% for quetiapine and 11.4% for placebo. In short-term, placebo-controlled clinical trials in bipolar depression the aggregated incidence of extrapyrimidal symptoms was 8.9% for quetiapine compared to 3.8% for placebo, though the incidence of the individual adverse events (e.g., akathisia, extrapyramidal disorder, tremor, dyskinesia, dystonia, restlessness, muscle contractions involuntary, psychomotor hyperactivity and muscle rigidity) were generally low and did not exceed 4% in any treatment group). In short-term, placebo controlled monotherapy trial in major depressive disorder the aggregated incidence of extrapyramidal symptoms was 5.4% for Seroquel XR and 3.2% for placebo. In a short-term placebo controlled monotherapy in elderly patients with major depressive disorder, the aggregated incidence of extrapyrimidal symptoms was 9.0% for Seroquel XR and 2.3% for placebo. In long-term studies of schizophrenia, bipolar disorder and major depressive disorder the aggregated incidence of treatment-emergent extrapyrimidal symptoms was similar between quetiapine and placebo.
Thyroid Level: Quetiapine treatment was associated with small dose-related decreases in thyroid hormone levels, particularly total T4 and free T4. The reduction in total and free T4 was maximal within the first two to four weeks of quetiapine treatment, with no further reduction during long-term treatment. In nearly all cases, cessation of quetiapine treatment was associated with a reversal of the effects on total and free T4, irrespective of the duration of treatment. Smaller decreases in total T3 and reverse T3 were seen only at higher doses. Levels of TBG were unchanged and in general, reciprocal increases in TSH were not observed, with no indication that quetiapine causes clinically relevant hypothyroidism.
Children and adolescents (10 to 17 years of age): The same ADRs described in previously mentioned for adults should be considered for children and adolescents. Based on clinical data with Seroquel the following table summarises ADRs that occur in a higher frequency category in children and adolescent s patients (10-17 years of age) than in the adult population or ADRs that have not been identified in the adult population. (See Table 2.)
Click on icon to see table/diagram/image
Weight Gain in Children and Adolescents: In one 6-week, placebo-controlled trial in adolescent patients (13-17 years of age) with schizophrenia, the mean increase in body weight, was 2.0 kg in the Seroquel group and -0.4 kg in the placebo group. Twenty-one percent of Seroquel-treated patients and 7% of placebo-treated patients gained ≥7 % of their body weight.
In one 3-week, placebo-controlled trial in children and adolescent patients (10-17 years of age) with bipolar mania, the mean increase in body weight was 1.7 kg in the Seroquel group and 0.4 kg in the placebo group. Twelve percent of Seroquel-treated patients and 0% of placebo-treated patients gained ≥7 % of their body weight.
In the open-label study that enrolled patients from the above two trials, 63% of patients (241/380) completed 26 weeks of therapy with Seroquel. After 26 weeks of treatment, the mean increase in body weight was 4.4 kg. Forty-five percent of the patients gained ≥7% of their body weight, not adjusted for normal growth. In order to adjust for normal growth over 26 weeks an increase of at least 0.5 standard deviation from baseline in BMI was used as a measure of a clinically significant change; 18.3% of patients on Seroquel met this criterion after 26 weeks of treatment.
Extrapyramidal Symptoms in Children and Adolescent Population: In a short-term placebo-controlled monotherapy trial in adolescent patients (13-17 years of age) with schizophrenia, the aggregated incidence of extrapyramidal symptoms was 12.9% for Seroquel and 5.3% for placebo, though the incidence of the individual adverse events (eg, akathisia, tremor, extrapyramidal disorder, hypokinesia, restlessness, psychomotor hyperactivity, muscle rigidity, dyskinesia) was generally low and did not exceed 4.1% in any treatment group. In a short-term placebo-controlled monotherapy trial in children and adolescent patients (10-17 years of age) with bipolar mania, the aggregated incidence of extrapyramidal symptoms was 3.6% for Seroquel and 1.1% for placebo.