New data shows that Seroquel reduces aggression in a wide range of people with psychotic disorders, and is well tolerated

FOR IMMEDIATE RELEASE

NEW DATA SHOWS SEROQUEL REDUCES AGGRESSION IN A WIDE RANGE OF PEOPLE WITH PSYCHOTIC DISORDERS, AND IS WELL TOLERATED

SAN DIEGO - March 8, 1998 - Scientific research presented today at the annual meeting of the American Association for Geriatric Psychiatry (AAGP) shows that SEROQUEL(R) (quetiapine fumarate) tablets, the newest of the atypical antipsychotics, reduces hostility and aggression in people with psychotic disorders, including schizophrenia and Alzheimer's disease.(1,2)

Although standard antipsychotics can reduce aggression and hostility in patients with acute psychosis, they can also produce undesirable side effects such as cognitive dysfunction and extrapyramidal symptoms (EPS), including rigidity, stiffness, shaking, and difficulty starting and stopping movement. "Elderly patients with psychotic disorders are less able to tolerate the development of these side effects. Therefore, an effective antipsychotic with a low incidence of these effects, such as SEROQUEL, is particularly desirable in this patient population," said Marc Cantillon M.D., Associate Medical Director of Medical Affairs, CNS, at Zeneca Pharmaceuticals in Wilmington, DE.

"SEROQUEL represents an important advancement in the treatment of psychotic disorders, particularly for those patients with tendencies towards aggressive or hostile behavior, which can also coexist with Alzheimer's disease and other conditions in the elderly," continued Dr. Cantillon. "Clinical trials demonstrate that therapy with SEROQUEL is well tolerated and benefits many patients with schizophrenia by controlling both positive and negative symptoms of the disease."

A six-week, placebo-controlled, double-blind, randomized trial of 351 patients with acute exacerbation of schizophrenia showed that SEROQUEL was superior to placebo in reducing positive and negative symptoms(3) and also superior on all three measures of aggression and hostility - without producing EPS.(1) In another multicenter, open-label trial in 151 elderly patients (aged 65 and over) with psychotic disorders, SEROQUEL was shown to be effective in the treatment of psychosis in the elderly, reducing both positive and negative symptoms, with no major safety concerns.(2) There was a clear drop in overall psychopathology, including delusions, hallucinations, and other symptoms of psychosis. A significant proportion of the improvements noted were in patients displaying aggression and hostility, which are a major problem in the care of the elderly, not only in outpatient settings, but also in medical / surgical units of hospitals and long-term care nursing homes.(2)

The study amongst elderly patients with idiopathic and organic psychosis2 evaluated the efficacy, safety, and tolerability of SEROQUEL (25-800 mg/day). Idiopathic psychosis included bipolar disorder, depression, and schizophrenia; organic psychosis included Alzheimer's and Parkinson's disease and other dementias. The results showed that SEROQUEL was effective in the treatment of psychosis in the elderly, reducing both positive and negative symptoms, including aggression and hostility, and was also well tolerated with no major safety concerns arising.

The six week study(1,3) evaluated five fixed doses of SEROQUEL (75, 150, 300, 600, and 750 mg/day) and a single haloperidol dose (12 mg/day). Aggression and hostility were assessed using several Brief Psychiatric Rating Scale (BPRS) areas. SEROQUEL and haloperidol were both superior to placebo in reducing positive and negative symptoms; however, only SEROQUEL was superior to placebo on all three measures of aggression and hostility (at a dose of 600 mg/day). Unlike haloperidol, SEROQUEL did not produce treatment-emergent or dose-related EPS or elevated levels of plasma prolactin.

"Due to its favorable safety and tolerability profile across the entire dose range, in addition to data supporting efficacy in treating positive and negative symptoms of schizophrenia, SEROQUEL represents a beneficial treatment option for this devastating mental illness," added Dr. Cantillon.

Schizophrenia is a severe, chronic, brain disorder which affects nearly three million - or one in every 100 - Americans(4) and it is estimated that the disease results in as much as $65 billion annually in direct medical costs and lost productivity.(5)

About SEROQUEL SEROQUEL tablets were cleared for marketing by the US Food and Drug Administration (FDA) on September 26, 1997, for the management of the manifestations of psychotic disorders including schizophrenia. SEROQUEL is effective in treating both the positive and negative symptoms of schizophrenia.

SEROQUEL belongs to the new chemical class of atypical antipsychotics known as dibenzothiazepine derivatives and is available by prescription in strengths of 25mg, 100mg, and 200mg tablets. In clinical trials, efficacy was demonstrated in a dose range of 150 mg/day to 750 mg/day. A maximum therapeutic effect was seen at 300 mg/day in a dosing trial. A dosing regimen of two to three times daily is recommended.

In three placebo- and comparator-controlled Phase II and III clinical trials, SEROQUEL was shown to be effective in treating both the positive symptoms (ie, hallucinations, delusions) and negative symptoms (ie, emotional withdrawal, blunted affect) associated with schizophrenia. SEROQUEL was well tolerated in more than 4,000 male and female patients 18 years and older. The safety and effectiveness of SEROQUEL in pediatric patients younger than 18 years of age have not been established.

As with other atypical antipsychotic agents, the labeling for SEROQUEL includes a warning relative to tardive dyskinesia (often associated with long-term use of antipsychotic agents) and neuroleptic malignant syndrome (NMS). Symptoms of NMS include muscle rigidity or irregular pulse. Precautions include orthostatic hypotension (which may result in dizziness) and tachycardia (fast heartbeat). Similar to other antipsychotics, SEROQUEL should be used cautiously in patients with a history of seizures or conditions that can potentially lower the seizure threshold.

The most common adverse events included somnolence (18% v. placebo 11%), headache (19% v. placebo 18%), and dizziness (10% v. placebo 4%), and the majority of events rated as mild or moderate. The incidence of EPS with SEROQUEL was not different from placebo across the clinical dose range.

SEROQUEL was discovered and developed by Zeneca Pharmaceuticals in its US research laboratories in Wilmington, DE and is available to physicians throughout the US.

About Zeneca Pharmaceuticals Zeneca Pharmaceuticals is a business unit of Zeneca Inc., a $3.1 billion bioscience business with approximately 7,200 employees in the US. Zeneca Inc. is a wholly-owned subsidiary of the UK-based Zeneca Group PLC (NYSE:ZEN), a major $9 billion international bioscience business engaged in the research, development, manufacturing, and marketing of ethical (prescription) pharmaceuticals, agricultural and specialty chemical products, and the supply of health care services.

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References

(1) Cantillon M., Arvanitis L., Miller B., Kowalcyk B.; Medical Research and Communications Group, Zeneca Pharmaceuticals, Wilmington, DE 19850; "Quetiapine Fumarate Reduces Aggression"; American Association for Geriatric Psychiatry, March 1998.

(2) Arvanitis L.A., Rak I.W.; Clinical Research, Zeneca Pharmaceuticals, Wilmington, DE 19850; Efficacy, Safety, and Tolerability of 'Seroquel' (Quetiapine) in Elderly Subjects with Psychotic Disorders. Schizophrenia Research. 1997; 24(1,2): 196.

(3) Arvanitis L.A., Miller B.G., and the Seroquel Trial 13 Study Group; Multiple Fixed Doses of 'Seroquel' (Quetiapine) in Patients with Acute Exacerbation of Schizophrenia: A Comparison with Haloperidol and Placebo. Biol Psychiatry. 1997; 42: 233-246.

(4) National Institute of Mental Health. Schizophrenia Questions and Answers, DHHS Publication No. (ADM) 86-1475.

(5) Wyatt R.J., et al. An economic evaluation of Schizophrenia. Soc Psychiatry Epidemol (GERMANY). 1995; 30(5): 196-205.