Quetiapine versus other atypical antipsychotic drugs for schizophrenia

Quetiapine is a second-generation antipsychotic. Second-generation or atypical antipsychotic drugs have become the mainstay of treatment in many countries for people with schizophrenia. They are called second-generation drugs because they are newer than the older drugs, known as typical antipsychotics. Second-generation drugs are thought to be better than the older drugs in reducing the symptoms of schizophrenia, such as hearing voices and seeing things, and are suggested to produce fewer side effects, such as sleepiness, weight gain, tremors and shaking. However, it is not clear how the various second- generation antipsychotic drugs differ from one other. The aim of this review therefore was to evaluate the effects of quetiapine compared with other second-generation antipsychotic drugs for people with schizophrenia. The review included a total of 35 studies with 5971 people, which provided information on six comparisons (quetiapine vs the following: clozapine, olanzapine, risperidone, ziprasidone, paliperidone and aripiprazole). Comparisons with amisulpride, sertindole and zotepine do not exist, so more research is needed. A major limitation of all findings was the large number of people leaving studies and stopping quetiapine treatment (50.2% of people). The most important finding to note is that if a group is started on quetiapine, most will be off this drug within a few weeks (although the reasons for stopping quetiapine treatment are not covered by the review and so remain uncertain). Quetiapine may be slightly less effective than risperidone and olanzapine in reducing symptoms, and it may cause less weight gain and fewer side effects and associated problems (such as heart problems and diabetes) than olanzapine and paliperidone, but more than are seen with risperidone and ziprasidone. The limited information tends to suggest that people taking quetiapine may need to be hospitalised more frequently than those taking risperidone or olanzapine. This may lead to higher costs in some settings, but the information is not robust enough to guide managers.

This summary has been written by a consumer, Ben Gray (Benjamin Gray, Service User and Service User Expert, Rethink Mental Illness).

Authors' conclusions: 

Available evidence from trials suggests that most people who start quetiapine stop taking it within a few weeks (around 60%). Comparisons with amisulpride, sertindole and zotepine do not exist. Although efficacy data favour olanzapine and risperidone compared with quetiapine, the clinical meaning of these data remains unclear. Quetiapine may produce fewer parkinsonian effects than paliperidone, aripiprazole, ziprasidone, risperidone and olanzapine. Quetiapine appears to have a similar weight gain profile to risperidone, as well as clozapine and aripiprazole (although data are very limited for the latter two comparators). Quetiapine may produce greater weight gain than ziprasidone and less weight gain than olanzapine and paliperidone. Most data that have been reported within existing comparisons are of very limited value because of assumptions and biases within them. Much scope is available for further research into the effects of this widely used drug.

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Background: 

In many countries, second-generation ('atypical') antipsychotic drugs have become the first-line drug treatment for people with schizophrenia. It is not clear how the effects of the various second-generation antipsychotic drugs differ.

Objectives: 

To evaluate the effects of quetiapine compared with other second-generation (atypical) antipsychotic drugs in the treatment of people with schizophrenia and schizophrenia-like psychoses.

Search strategy: 

We searched the Cochrane Schizophrenia Group Trials Register (May 2010), inspected references of all identified studies, and contacted relevant pharmaceutical companies, drug approval agencies and authors of trials for additional information.

Selection criteria: 

We included all randomised controlled trials (RCTs) comparing oral quetiapine with other oral forms of atypical antipsychotic medication in people with schizophrenia or schizophrenia-like psychoses.

Data collection and analysis: 

We extracted data independently. For dichotomous data, we calculated risk ratios (RRs) and their 95% confidence intervals (CIs) on an intention-to-treat basis based on a random-effects model. We calculated number needed to treat for an additional beneficial outcome (NNTB) where appropriate. For continuous data, we calculated mean differences (MDs), again based on a random-effects model.

Main results: 

Efficacy data tended to favour the control drugs over quetiapine (Positive and Negative Syndrome Scale (PANSS) total score vs olanzapine: 11 RCTs, n = 1486, mean quetiapine endpoint score 3.67 higher, CI 1.95 to 5.39, low quality; vs risperidone: 13 RCTs, n = 2155, mean quetiapine endpoint score 1.74 higher, CI 0.19 to 3.29, moderate quality; vs paliperidone: 1 RCT, n = 319, mean quetiapine endpoint score 6.30 higher, CI 2.77 to 9.83, moderate quality), but the clinical meaning of these data is unclear. No clear mental state differences were noted when quetiapine was compared with clozapine, aripiprazole or ziprasidone. Compared with olanzapine, quetiapine produced slightly fewer movement disorders (7 RCTs, n = 1127, RR use of antiparkinson medication 0.51, CI 0.32 to 0.81, moderate quality) and less weight gain (8 RCTs, n = 1667, RR 0.68, CI 0.51 to 0.92, moderate quality) and glucose elevation, but increased QTc prolongation (3 RCTs, n = 643, MD 4.81, CI 0.34 to 9.28). Compared with risperidone, quetiapine induced slightly fewer movement disorders (8 RCTs, n = 2163, RR use of antiparkinson medication 0.5, CI 0.36 to 0.69, moderate quality), less prolactin increase (7 RCTs, n = 1733, MD -35.25, CI -43.59 to -26.91) and some related adverse effects but greater cholesterol increase (6 RCTs, n = 1473, MD 8.57, CI 4.85 to 12.29). On the basis of limited data, compared with paliperidone, quetiapine induced fewer parkinsonian side effects (1 RCT, n = 319, RR use of antiparkinson medication 0.64, CI 0.45 to 0.91, moderate quality) and less prolactin increase (1 RCT, n = 319, MD -49.30, CI -57.80 to -40.80) and weight gain (1 RCT, n = 319, RR weight gain of 7% or more of total body weight 2.52, CI 0.5 to 12.78, moderate quality). Compared with ziprasidone, quetiapine induced slightly fewer extrapyramidal adverse effects (1 RCT, n = 522, RR use of antiparkinson medication 0.43, CI 0.2 to 0.93, moderate quality) and less prolactin increase. On the other hand, quetiapine was more sedating and led to greater weight gain (2 RCTs, n = 754, RR 2.22, CI 1.35 to 3.63, moderate quality) and cholesterol increase when compared with ziprasidone.

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