Quetiapine fumarate

Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Seroquel (AstraZeneca)
25 mg, 100 mg and 200 mg tablets
Approved indication: schizophrenia
Australian Medicines Handbook Section 18.2.2

Quetiapine is one of the 'new anti-psychotics'.1 Itacts by antagonising neurotransmitters at several receptors. The affinity of quetiapine for dopamine receptors (D2) is relatively low compared to its affinity for 5HT2 receptors. It also has little affinity for cholinergic receptors.

Patients take quetiapine twice a day. For the first four days of treatment the dose is increased each day. It is then adjusted according to the patient's response.

Each dose is rapidly absorbed and widely distributed. Quetiapine is extensively metabolised by the liver and then excreted in the urine and faeces. CytochromeP450 (CYP 3A4) is probably primarily responsible for the metabolism. Extra caution is needed if quetiapine is given with inhibitors of this enzyme including some antidepressants. The clearance of quetiapine will be increased by drugs such as phenytoin which induce hepatic enzymes. Hepatic or renal impairment will reduce the clearance of quetiapine. Although its half-life is seven hours, quetiapine occupies the 5HT2 and D2 receptors for up to 12 hours.

Quetiapine can cause postural hypotension so it should be used with caution in patients with cardiovascular disease. Other common adverse effects are somnolence, dry mouth, constipation, dizziness and altered liver function. Quetiapine may mildly prolong the QTc interval so caution is needed if it is prescribed with other drugs which have this effect. In the USA patients are advised to have their eyes checked every six months because cataracts developed in some animal studies. This precaution is not included in the Australian product information.

Short-term studies have found quetiapine to be as effective as chlorpromazine and haloperidol, but it has a lower incidence of dystonia. In a comparison with risperidone, quetiapine was effective for the treatment of exacerbations of schizophrenia. Approximately 33% of the patients taking quetiapine and 38%of those taking risperidone had at least a 40% reduction in their positive and negative symptom scores. The long-term effectiveness of quetiapine requires further study.

A Cochrane review has found that quetiapine causes no more extra pyramidal effects than placebo and may be more effective. However, the review concludes that more studies are needed before quetiapine can be recommended. Many of the studies in the review had high dropout rates (48-61%) which make the results difficult to interpret.2

References

  1. McGrath J, White P. New antipsychotic medications. Aust Prescr 1999;22:81-3.
  2. Srisurapanont M, Disayavanish C, Taimkaew K. Quetiapine for schizophrenia (Cochrane Review). In: The Cochrane Library, Issue 3, 1999.Oxford: Update software.