NPC Archive Item: Aripiprazole versus conventional (typical) antipsychotics for schizophrenia

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MeReC Rapid Review

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Bhattacharjee J, El-Sayeh HGG. Aripiprazole versus typicals for schizophrenia. Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD006617. DOI: 10.1002/14651858.CD006617.pub2

What is the background to this? – Aripiprazole is a relatively new atypical antipsychotic, which is licensed for the treatment of schizophrenia. A recent Cochrane review of randomised controlled trials (RCTs) has considered the efficacy and safety of aripiprazole compared with conventional (typical) antipsychotics, such as haloperidol.

What did the review find? – Aripiprazole and conventional antipsychotics had similar efficacy with regard to symptom improvement. Aripiprazole appeared to offer a favourable adverse-effect profile, with a significantly lesser risk of causing extra-pyramidal symptoms, hyperprolactinaemia, raised blood glucose and sinus tachycardia. However aripiprazole is more commonly associated with nausea and dizziness. The authors of the review considered that its better tolerability may encourage better compliance.

How does this relate to NICE guidelines?NICE guidance from 2002 recommends oral atypical antipsychotic drugs (amisulpride, olanzapine, quetiapine, risperidone and zotepine) as first-choice treatments for individuals with newly diagnosed schizophrenia. Aripiprazole was not considered as part of this guideline. The guideline recommends that the choice of antipsychotic drug should be made jointly by the individual and the clinician responsible for treatment based on an informed discussion of the relative benefits of the drugs and their side-effect profiles. It also emphasises the need for GPs and other primary health workers to regularly monitor the physical health of people with schizophrenia registered with their practice. Where conventional antipsychotics are used and are not effective or are causing unacceptable side effects, an atypical agent is recommended. If an atypical is causing diabetes or excessive weight gain, consideration should be given to changing to a different atypical or a conventional antipsychotic. This is explored in more detail on the schizophrenia section of NPC.

So what? Although no efficacy advantage for aripiprazole has been demonstrated over typical antipsychotics, this review suggests that it may be better tolerated by some patients with schizophrenia. However, most of the studies on which the review was based were short-term and data reporting was considered to be poor. Although aripiprazole is suggested to offer a possible advantage over conventional antipsychotics regarding compliance, the attrition rate of patients receiving aripiprazole in this one long-term study reported was still very high at 57%.  Unfortunately, none of the studies in this review reported relapse, which is the outcome of most interest once an acute episode has been controlled.

As demonstrated in the CATIE study, there is little difference in effectiveness between atypical or conventional antipsychotics (see MeReC Extra No. 23, July 2006). All are associated with a high rate of intolerable side effects and failure to control symptoms, with a high rate of discontinuation. There is no evidence that aripiprazole is different in this regard. Further longer-term data, especially those comparing aripiprazole with other atypical antipsychotics, are required before it can be recommended for routine use ahead of other more established less expensive atypical antipsychotics; however, aripiprazole may be an option to consider where they are ineffective or not tolerated. Careful monitoring of physical health and side effects with aripiprazole is required, as with any antipsychotic.

Action – The NICE guideline recommendations for the prescribing and monitoring of antipsychotics should continue to be followed. Prescribing of antipsychotics is generally carried out in secondary care, and GPs should consider referring patients where adherence to treatment is poor, or they suffer unacceptable side effects. Aripiprazole is an option where an atypical is antipsychotic is indicated, but other more established agents are not effective or not tolerated.

Study details:
Studies included – nine RCTs involving 3122 people comparing aripiprazole with typical antipsychotic drugs were included.
Outcomes measured –  Improvements in global and mental state were generally similar for aripiprazole and typical antipsychotics.
Results – There were statistically significant advantages for aripiprazole over typical antipsychotics with regard to:

  • fewer occurrences of extra-pyramidal symptom (n=968; 3 RCT; relative risk [RR] 0.46, 95%CI 0.3 to 0.9; number needed to treat [NNT] 13, 95%CI 17 to 10), and particularly,
  • akathisia (n=897; 3 RCT; RR 0.39 95%CI 0.3 to 0.6; NNT 11, 95%CI 14 to 9).
  • Development of hyperprolactinaemia (n=300; 1 RCT; RR 0.07 95%CI 0.03 to 0.2; NNT 2, 95%CI 3 to 1)
  • raised fasting blood glucose (n=360; 1 RCT; RR 0.65, 95%CI 0.5 to 0.9; NNT 8, 95%CI 14 to 6).
  • Sinus tachycardia (n=289; 1 RCT; RR 0.09, 95%CI 0.01 to 0.8; NNT 22, 95%CI 63 to 13)
  • Blurred vision (n=308, 1 RCT, RR 0.19 95%CI 0.1 to 0.7, NNT 14 95%CI 25 to 10).
  • However people taking aripiprazole had a higher rate of:

  • dizziness (n=957; 3 RCTs; RR 1.88, 95%CI 1.1 to 3.2; number needed to harm [NNH] 20, 95%CI 33 to 14) and,
  • nausea (n=957, 3 RCTs, RR 3.03 95%CI 1.5 to 6.1, NNH 17 95%CI 25 to 13).

    For further information on the treatment of schizophrenia please visit the CNS and Mental Health section on NPC.

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