In pooled data from 3- to 6-week trials, 23% of patients receiving quetiapine and 6% of patients receiving placebo gained � 7% of their baseline body weight {01}. Two possible cases were reported during clinical trials with quetiapine {01}. Quetiapine has no significant affinity for cholinergic muscarinic or benzodiazepine receptors {01}. , clozapine, risperidone, olanzapine, quetiapine, ziprasidone) are at an increased risk of developing hyperglycemia and/or diabetes mellitus. However, the mean plasma clearance of quetiapine in elderly patients was 30 to 50% less than in younger patients {01}. Although the results were not definitive, quetiapine toxicity studies in rats and mice showed changes in thyroxine concentrations, thyroxine clearance, and TSH concentrations that are consistent with the proposed mechanism of increased thyroxine clearance leading to increased TSH concentrations and increased thyroid gland stimulation {01}. The effectiveness of quetiapine for more than 6 weeks has not been evaluated in controlled trials {01}{02}. , risperidone, olanzapine, clozapine, quetiapine) increase the risk of venous thromboembolism in elderly patients; however, these events seem to be rare. However, the possibility of a diminished therapeutic response to quetiapine should be considered in patients receiving concomitant therapy with these agents. Drowsiness and orthostatic hypotension associated with use of quetiapine may be explained by its antagonism of histamine H 1 and adrenergic alpha 1 receptors, respectively {01}. Eleven months later, quetiapine was introduced and the patient once again developed acute symptoms of cholestasis which later resolved after quetiapine discontinuation. It is not known whether quetiapine is distributed into *** milk, but ***-feeding while taking quetiapine is not recommended {01}{02}. Although clinical data are lacking, the possibility of prolonged and/or increased pharmacologic effects of quetiapine should be considered. Caution is advised in administering quetiapine to patients who will be experiencing conditions that may contribute to an elevation in core body temperature, such as strenuous exercise, exposure to extreme heat, dehydration, or concomitant treatment with anticholinergic medications {01}. In ten subjects with various affective disorders, phenytoin (100 mg orally three times a day) decreased the mean steady-state peak plasma concentration (Cmax), trough plasma concentration (Cmin) and area under the concentration-time curve (AUC) of quetiapine (250 mg orally three times a day) by 66%, 89% and 80%, respectively, compared to administration of quetiapine alone. For these reasons, quetiapine should be used only in those patients with chronic illness that is responsive to antipsychotic medication, and for whom potentially less harmful treatments are unavailable or inappropriate {01}. However, disopyramide, procainamide, and quinidine have the potential to add to the possible QT-interval–prolonging effects of quetiapine overdosage {01}. MANAGEMENT: Pharmacologic response to quetiapine should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy, and the quetiapine dosage adjusted as necessary. If signs and symptoms of tardive dyskinesia appear, discontinuation of quetiapine treatment should be considered if clinically feasible {01}{02}. In ten subjects with various affective disorders, the 3A4 inducer phenytoin (100 mg orally three times a day) decreased the mean steady-state peak plasma concentration (Cmax), trough plasma concentration (Cmin) and area under the concentration-time curve (AUC) of quetiapine (250 mg orally three times a day) by 66%, 89% and 80%, respectively. Also, bretylium may add to the hypotensive effect of quetiapine, due to additive alpha-adrenergic receptor blockade {01}.
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