Seroquel® 
An atypical antipsychotic for the treatment of schizophrenia

Licensed Indication:
Quetiapine ‘is indicated for the treatment of schizophrenia.’

Clinical Efficacy:
The Cochrane Library has published a systematic review of quetiapine for the treatment of schizophrenia. This review pooled data from 11, short-term, randomised controlled trials (n = 2725) and was last updated in May 2000. Apart from one study of 21 days (n=12), and one of 6 months (n= 25), the other nine were of 6 or 8 weeks duration.

Three of the 11 studies compared quetiapine solely with placebo, and 7 to typical antipsychotics (chiefly haloperidol). The remaining study was a non-comparative dose-frequency trial. The daily dose range of quetiapine evaluated across the studies was 50- 750mg. The mean daily dose of haloperidol evaluated ranged from 6.7- 20mg.

In these short-term studies, quetiapine treatment improved patients global state and psychotic symptoms compared to placebo. Similar efficacy was seen compared with the typical antipsychotics.

Limited longer-term data on quetiapine treatment of up to 4 years have been reported in poster presentations and as data on file. These results suggest that improvements in symptoms seen with quetiapine during short-term clinical trials are maintained over the longer term.

There are no fully published comparisons of quetiapine with other atypical antipsychotics in patients with schizophrenia. However, data from a 4-month open-label study comparing quetiapine with risperidone in patients with psychotic disorders (~35% with schizophrenia) have been published in a poster presentation (n=751). The results, presented graphically only, appear to

demonstrate similar efficacy with quetiapine and risperidone (mean daily doses 317mg and 4.5mg respectively).

Safety:
The most common adverse events seen with quetiapine in clinical trials were somnolence, postural dizziness, hypotension, headache, and dry mouth. The incidence of extrapyramidal symptoms (EPS) and the need for anticholinergic medication with quetiapine was similar to placebo, and less than with the typical antipsychotics. Quetiapine was associated with some weight gain.

In clinical trials, 13 of 826 patients treated with quetiapine (compared with 2 of 155 with placebo) had clinically significant prolongation of the QTc interval (>0.5 seconds). One of these 13 patients experienced a cardiovascular event (tachycardia upon standing). Caution is advised when quetiapine is prescribed with drugs known to prolong the QTc interval, especially in the elderly.

Additional Information:
The daily dose of quetiapine should be titrated from 50mg to 300mg over days 1-4 of therapy. Thereafter, the daily dose should be titrated to the usual effective range of 300- 450mg (to a maximum of 750mg) depending on the patient's clinical response and tolerability. The starting dose and dosage increments should be lower in elderly patients and patients with renal and hepatic impairment (refer to Summary of Product Characteristics). Quetiapine should be administered twice daily, with or without food.

At current prices, one year’s treatment costs:

• £1376–£2064 with quetiapine 300-450mg/day
• £940–£1424 with risperidone 4-6mg/day
• £1272–£2544 with olanzapine 10-20mg/day
• £87–£154 with haloperidol 10-20mg/day.

This guidance is based on the published information available at the time the drug was considered. It remains open to review in the event of significant new evidence emerging.

THIS VERDICT SHEET REPLACES VS97/22 WHICH SHOULD BE REMOVED AND DESTROYED

WARNING: This sheet should be read in conjunction with the Summary of Product Characteristics (Datasheet)

RELEVANT NICE GUIDANCE WAS NOT AVAILABLE AT THE TIME OF ISSUE OF THIS VERDICT