Seroquel (quetiapine) is an atypical antipsychotic agent indicated for Bipolar Disorder including Bipolar Depression, Bipolar Mania, Bipolar Maintenance, and Schizophrenia. It is also used off-label for a variety of other purposes, including insomnia and anxiety disorders.
The antipsychotic effect of quetiapine is thought by some to be mediated through antagonist activity at dopamine and serotonin receptors. Specifically the D1 and D2 dopamine receptor, the alpha-1 and alpha-2 adrenergic receptor, and 5-HT1A and 5-HT2 serotonin receptor subtypes are antagonized. Serial PET scans evaluating the D2 receptor occupancy of quetiapine have demonstrated that quetiapine very rapidly disassociates from the D2 receptor. Theoretically, this allows for normal physiological surges of dopamine to elicit their normal effects in areas such as the nigrostriatal and tuberoinfundibular pathways, thus minimizing the risk of side effects such as pseudo-parkinsonism as well as elevations in prolactin. Quetiapine also has an antagonistic effect on the histamine H1 receptor. This is thought to be responsible for the sedative effect of the drug.
The most common side effect of quetiapine is sedation, and it is marketed as one of the most sedating of all antipsychotics, albeit those efficacy claims are contested. Beginning users may feel extremely tired and 'out of it' for the first few days, sometimes longer. Quetiapine's newest indication, for bipolar depression, usually specifically calls for the entire dose to be taken before bedtime due to its sedative effects. Although quetiapine is approved by the FDA only for the treatment of schizophrenia and bipolar disorder, it is frequently prescribed off-label for other purposes, including insomnia and the treatment of anxiety disorders. The sedative effects may disappear after some time on the drug, or with a change of dosage, and with possibly different, non-sedative side effects emerging.
Common side effects include weight gain, constipation, headache and dry mouth. Six to seven percent of patients may experience tachycardia. Less common side effects (less than 1% of patients) include abnormal liver tests, dizziness, upset stomach, substantial weight gain, a stuffy nose, akathisia and increased paranoia. There is a risk of development of tardive dyskinesia, an incurable neurological disorder, with any prolonged use of quetiapine and some other neuroleptic drugs. However, quetiapine is believed to cause tardive dyskinesia somewhat less often than typical antipsychotics based on the data sources which point to placebo-level incidence of extrapyramidal side effects. The rare, but life-threatening, neuroleptic malignant syndrome may also result from quetiapine use. Weight gain can be a problem for some patients using quetiapine, by causing the patient's appetite to persist even after meals. However, this effect may occur to a lesser degree compared to some other atypical antipsychotics such as olanzapine or clozapine. As with other atypical antipsychotics, there is evidence suggesting a link to the development of diabetes and blood sugar disorders, however this remains controversial due to disparities between the results of studies.
While there are reports of cataracts occurring in humans, controlled studies including thousands of patients have not demonstrated a clear causal association between quetiapine therapy and this side effect. (Reference needed to April 2006 results of CATIE study.) However, the Seroquel website still recommends users have eye examinations every six months.
As with some other antipsychotics, quetiapine may lower the seizure threshold, and should be taken with care in combination with drugs such as bupropion.
Its use is contraindicated with concomitant use of cisapride, phenothiazines, and triptorelin
Dustin Wilkes, MS III
J. Patrick Bertroche, DO
