Quetiapine versus typical antipsychotic drugs for schizophrenia

Antipsychotic drugs are the main treatment for schizophrenia, helping to treat both the positive symptoms (such as hearing voices, seeing things and having strange beliefs) and negative symptoms (including apathy, tiredness and loss of emotion) of this illness. Selecting the most effective antipsychotic drug that can be tolerated by people with schizophrenia is crucial to successful treatment. Older drugs (also known as typical or first generation antipsychotic drugs), such as chlorpromazine and haloperidol, have been used in treating schizophrenia for over 50 years. Although these older drugs are good at treating the positive symptoms of schizophrenia they tend to cause undesirable side effects. These side effects can mean that people do not tolerate or like taking these drugs, which may lead to relapse and admission to hospital. Since 1988, a newer generation of antipsychotic drugs has become available. These new drugs (known as atypical or second generation antipsychotic drugs) are effective in treating the symptoms of schizophrenia but thought to have less side effects than older drugs. However, although newer drugs may cause less side effects such as movement disorders, they have been linked to other side effects like heart problems or weight gain. Quetiapine is a new antipsychotic drug for schizophrenia that has been available for over a decade. However, it is not clear how the effects of quetiapine differ from older antipsychotic drugs. This review evaluated the effectiveness and tolerability of quetiapine versus older antipsychotic drugs. The review included 43 trials with a total of 7217 people. Most studies were from China. In the main, quetiapine did not differ from older drugs for the treatment of positive symptoms of mental illness. There were also no clear differences in terms of the treatment of negative symptoms. However, it is important to note that evidence from these trials suggests quetiapine causes fewer side effects (such as weight gain, dizziness, movement disorders, the inability to sit still, shaking, tremors and abnormal levels of the hormone prolactin, which can contribute to sexual and mental health problems). However, evidence from the trials is limited due to high numbers of people leaving early in almost all of the studies. More evidence through the completion of well designed studies comparing quetiapine with older antipsychotic drugs is needed.

This plain language summary has been written by a consumer, Benjamin Gray, Service User: RETHINK.

Authors' conclusions: 

Quetiapine may not differ from typical antipsychotics in the treatment of positive symptoms and general psychopathology. There are no clear differences in terms of the treatment of negative symptoms. However, it causes fewer adverse effects in terms of abnormal ECG, extrapyramidal effects, abnormal prolactin levels and weight gain.

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Background: 

Quetiapine is a widely used atypical antipsychotic drug for schizophrenia that has been on the market for over a decade. However, It is not clear how the effects of quetiapine differ from typical antipsychotics.

Objectives: 

To review the effects of quetiapine in comparison with typical antipsychotics in the treatment of schizophrenia and schizophrenia-like psychosis.

Search strategy: 

We searched the Cochrane Schizophrenia Group Trials Register (March 2010), and inspected references of all identified studies.

Selection criteria: 

We included all randomised control trials comparing oral quetiapine with typical antipsychotic drugs in people with schizophrenia or schizophrenia-like psychosis.

Data collection and analysis: 

We extracted data independently. For dichotomous data, we calculated risk ratio (RR) and 95% confidence intervals (CI) using a random-effects model. We presented chosen outcomes in a 'Summary of findings' table and comparative risks where appropriate. For continuous data, we calculated mean differences (MD) based on a random-effects model. We assessed risk of bias for included studies.

Main results: 

The review includes 43 randomised controlled trials (RCTs) with 7217 participants. Most studies were from China. The percentages of participants leaving the studies early were similar (36.5% in quetiapine group and 36.9% in typical antipsychotics group) and no significant difference between groups was apparent for leaving early due to any reason (23 RCTs n = 3576 RR 0.91 CI 0.81 to 1.01, moderate quality evidence), however, fewer participants in the quetiapine group left the studies early due to adverse events (15 RCTs, n = 3010, RR 0.48 CI 0.30 to 0.77).

Overall global state was similar between groups (no clinically significant response; 16 RCTs, n = 1607, RR 0.96 CI 0.75 to 1.23, moderate quality evidence) and there was no significant difference in positive symptoms (PANSS positive subscore: 22 RCTs, n = 1934, MD 0.02 CI -0.39 to 0.43, moderate quality evidence). General psychopathology was equivocal (PANSS general psychopathology subscore: 18 RCTs, n = 1569, MD -0.20 CI -0.83 to 0.42) between those allocated to quetiapine and typical antipsychotics. However, quetiapine was statistically significantly more efficacious for negative symptoms (PANSS negative subscore: 22 RCTs, n = 1934, MD -0.82 CI -1.59 to -0.04, moderate quality evidence), however, this result was highly heterogeneous and driven by two small outlier studies with high effect sizes. Without these two studies, there was no heterogeneity and no statistically significant difference between quetiapine and typical antipsychotics.

Compared with typical antipsychotics, quetiapine might cause fewer adverse effects (9 RCTs, n = 1985, RR 0.76 CI 0.64 to 0.90 number needed to treat to induce harm (NNTH) 10, CI 8 to 17), less abnormal ECG (2 RCTs, n = 165, RR 0.38 CI 0.16 to 0.92, NNTH 8, CI 4 to 55), fewer overall extrapyramidal effects (8 RCTs, n = 1,095, RR 0.17 CI 0.09 to 0.32, NNTH 3, CI 3 to 3, moderate quality evidence) and fewer specific extrapyramidal effects including akathisia, parkinsonism, dystonia and tremor. Moreover, it might cause lower prolactin level (4 RCTs, n = 1034, MD -16.20 CI -23.34 to -9.07, moderate quality evidence) and less weight gain compared with some typical antipsychotics in the short term (9 RCTs, n = 866, RR 0.52 CI 0.34 to 0.80, NNTH 8, CI 6 to 15).

However, there was no significant difference between the two groups in suicide attempt, suicide, death, QTc prolongation, low blood pressure, tachycardia, sedation, gynaecomastia, galactorrhoea, menstrual irregularity and white blood cell count.

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