In 2005, quetiapine and other antipsychotics were shown by the New England Journal of Medicine to be no more effective than perphenazine (Trilafon), a typical antipsychotic, for the treatment of schizophrenia. However, the subsequent CATIE trial, funded by AstraZeneca and other major pharmaceutical manufacturers, contradicted the 2005 study in certain instances.
A 2005 British Medical Journal report showed that quetiapine was ineffective in reducing agitation among Alzheimer's patients, whose consumption of the drug then constituted 29% of sales; in fact, quetiapine was found to make cognitive functioning worse in elderly patients with dementia.
Phase III trials are being conducted to prove quetiapine's efficacy in treating generalized anxiety disorder and major depressive disorder as of January 2007. The company expects to file a New Drug Application for treating generalized anxiety disorder in the second half of 2007 and for major depressive disorder in 2008.
AstraZeneca's patent for Seroquel expires in September 2011, which will allow other companies to manufacture and market quetiapine.
Quetiapine is controversially marketed to parents of moody and irritable teenagers in magazines such as PARADE and TV Guide. The National Institutes of Health recommends against the use of quetiapine and almost all other psychotropic medications (including all atypicals, most antidepressants, and all benzodiazepines) by children or those under 18, observing that teenagers taking quetiapine "may be more likely to think about harming or killing themselves or to plan or try to do so".
Quetiapine also has an antagonistic effect on the histamine H1 receptor. This is thought to be responsible for the sedative effect of the drug.
On May 18, 2007, AstraZeneca announced that the U.S. Food and Drug Administration has approved Seroquel XR for acute treatment of schizophrenia. During its 2007 Q2 earnings conference, AstraZeneca announced plans to launch Seroquel XR in the U.S. during August 2007. However, Seroquel XR has only become available in U.S. pharmacies after the FDA approved Seroquel XR for use as maintenance treatment for schizophrenia, in addition to acute treatment of the illness, on November 16, 2007. The company has not provided a reason for the delay of Seroquel XR's launch.
Quetiapine has multiple side effects, some of them common, a few of them serious and life-threatening.
The most common side effect of quetiapine is sedation. It is prescribed specifically (off-label) for this effect in patients with sleep disorders. It is one of the most sedating of all antipsychotics, rivaling even the most sedating older drugs. 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 for the treatment of schizophrenia and bipolar disorder, it is frequently prescribed for off-label 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 constipation, headache, dry mouth, weight gain (or loss). Less common side effects (less than 1% of patients) include abnormal liver tests, dizziness, upset stomach, substantial weight gain or weight loss, 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.
In the United States, two separate lawsuits—over claims that quetiapine use has led to diabetes—have been filed in federal court.
Studies conducted on beagles have resulted in the formation of cataracts—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.
Quetiapine is not currently classified as a controlled substance. Reports of quetiapine abuse have emerged in the medical literature, however. While the drug is usually abused through the crushing and snorting of tablets (insufflation), there have also been reports of intravenous abuse and intravenous co-administration with cocaine. A 2004 report recorded a 30% rate of inmate use in the Los Angeles County Jail, where the drug was obtained by inmates faking schizophrenic symptoms and resold under the street name "quell". Also known as "Susie-Q", the drug may be more commonly abused in prisons due to its capacity to be regularly prescribed as a sedative and the unavailability in prison of more commonly abused substances. A letter to the editor which appeared in the January 2007 American Journal of Psychiatry has proposed a “need for additional studies to explore the addiction-potential of quetiapine”. The letter reports that its authors are physicians who work in the Ohio correctional system. They report that “prisoners ... have threatened legal action and even suicide when presented with discontinuation of quetiapine” and that they have “not seen similar drug-seeking behavior with other second-generation antipsychotics of comparable efficacy”.