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Evidence summaries

Aripiprazole for Schizophrenia

Aripiprazole may be equally effective with typical and atypical antipsychotics in schizophrenia, and it may be more tolerable due to its favourable adverse effects profile. Level of evidence: "C"

A Cochrane review [Abstract] 1 included 15 studies with a total of 7 110 subjects. Study attrition was very large.

Compared with typical antipsychotics (n=2 868, 7 RCTs) there were no significant benefits for aripiprazole with regards to global state, mental state, quality of life or leaving the study early. Both groups reported similar rates of adverse effects, with the exception of akathisia (n= 955 RR 0.31 CI 0.2 to 0.6, NNT 20 CI 17 to 32) and the need for antiparkinson medication (n=1 854, 4 RCTs, RR 0.45 CI 0.3 to 0.6, NNT 4 CI 3 to 5) which were lower in those receiving aripiprazole.

When compared with olanzapine and risperidone, aripiprazole was no better or worse on outcomes of global state and leaving the study early. The rates of adverse effects were also similar, with the exception of less elevation of prolactin (n=301, 1 RCT, RR 0.04 CI 0.02 to 0.1, NNT 2 CI 1 to 2.5) and less prolongation of the average QTc (30 mg/day) (n=200, 1 RCT, WMD -10.0, CI -16.99 to -3.0) compared with risperidone.

Comment: The quality of evidence is downgraded by study quality (high drop-out rate) and indirectness (only 2 trials reported outcomes over 26 weeks and most lasted less than 12 weeks).

Another Cochrane review [Abstract] 2 included 9 trials with a total of 3 122 subjects comparing aripiprazole with typical antipsychotic drugs. One trial reported outcomes over 26 weeks and all others lasted less than 12 weeks. None of the studies reported on relapse. Participants given aripiprazole were comparable to those receiving typical drugs in improving global state and mental state. Aripiprazole provided a significant advantage over typical antipsychotics in terms of fewer occurrences of extra-pyramidal symptom (n=968, 3 RCT, RR 0.46 CI 0.3 to 0.9, NNT 13 CI 17 to 10), and particularly akathisia (n=897, 3 RCT, RR 0.39 CI 0.3 to 0.6, NNT 11 CI 14 to 9). Fewer participants given aripiprazole developed hyperprolactinaemia (n=300, 1 RCT, RR 0.07 CI 0.03 to 0.2, NNT 2 CI 3 to 1) and raised fasting blood glucose (n=360, 1 RCT, RR 0.65 CI 0.5 to 0.9, NNT 8 CI 14 to 6). Aripiprazole presented a lesser risk of sinus tachycardia (n=289, 1 RCT, RR 0.09 CI 0.01 to 0.8, NNT 22 CI 63 to 13) and blurred vision (n=308, 1 RCT, RR 0.19 CI 0.1 to 0.7, NNT 14 CI 25 to 10); but enhanced risk of occurrence of dizziness (n=957, 3 RCTs, RR 1.88 CI 1.1 to 3.2, NNH 20 CI 33 to 14) and nausea (n=957, 3 RCTs, RR 3.03 CI 1.5 to 6.1, NNH 17 CI 25 to 13). Attrition rates were high in both groups, although significantly more participants in the aripiprazole group completed the study in the long term (n=1 294, 1 RCT, RR 0.81 CI 0.8 to 0.9 NNT 8 CI 5 to 14).

Comment:The quality of evidence is downgraded by study quality (unclear allocation concealment) and indirectness (short follow-up times).

Third Cochrane review [Abstract]3 included 174 trials involving 17 244 participants with schizophrenia. Aripiprazole was compared with clozapine, quetiapine, risperidone, ziprasidone and olanzapine. The overall number of participants leaving studies early was 30% to 40%. The vast majority were short term with a duration of three to eight weeks and conducted in China.The overall number of participants leaving the studies early was considerable (35% to 40%), limiting the validity of the findings, but with no significant differences between groups.

  • Aripiprazole vs clozapine: there were no significant differences for global state (no clinically significant response, 29 RCTs, n = 2132); mental state (BPRS, 5 RCTs, n = 426); or leaving the study early for any reason (3 RCTs, n = 240). Quality of life score using the WHO-QOL-100 scale demonstrated significant difference, favouring aripiprazole (RR 2.59, CI 1.43 to 3.74; 2 RCTs, n = 132). General extrapyramidal symptoms (EPS) were no different between groups (8 RCTs, n = 520). No study reported general functioning or service use.
  • Aripiprazole vs quetiapine: there were no significant differences for global state (12 RCTs, n = 991); mental state (PANSS positive symptoms, 7 RCTs, n = 583); leaving the study early for any reason (2 RCTs, n = 168), or general EPS symptoms (4 RCTs, n = 348). Results were significantly in favour of aripiprazole for quality of life (WHO-QOL-100 total score, MD 2.60, CI 1.31 to 3.89; 1 RCT, n = 100). No study reported general functioning or service use.
  • Aripiprazole vs. risperidone: there were no significant differences for global state (80 RCTs, n = 6381); or leaving the study early for any reason (12 RCTs, n = 1239). Data were significantly in favour of aripiprazole for improvement in mental state using the BPRS (MD 1.33, CI 2.24 to 0.42; 5 RCTs, n = 570); with higher adverse effects seen in participants receiving risperidone of general EPS symptoms (RR 0.39, CI 0.31 to 0.50; 31 RCTs, n = 2605). No study reported general functioning, quality of life or service use.
  • Aripiprazole vs. ziprasidone: there were no significant differences for global state (6 RCTs, n = 442); mental state using the BPRS (1 RCT, n = 247); or leaving the study early for any reason (2 RCTs, n = 316). Weight gain was significantly greater in people receiving aripiprazole (RR 4.01, CI 1.10 to 14.60; 3 RCTs, n = 232). No study reported general functioning, quality of life or service use.
  • Aripiprazole vs. olanzapine: there were no significant differences for global state (11 RCTs, n = 1739); mental state using PANSS (11 RCTs, n = 1500); or quality of life using the GQOLI-74 scale (1 RCT, n = 68). Significantly more people receiving aripiprazole left the study early due to any reason (RR 1.15, CI 1.05 to 1.25; 9 RCTs, n = 2331) and significantly more people receiving olanzapine gained weight (RR 0.25, CI 0.15 to 0.43; 9 RCTs, n = 1538). None of the included studies provided outcome data for the comparisons of 'service use' or 'general functioning'.

Comment: The quality of evidence is downgraded by study quality (unclear allocation concealment, high drop-out rate) and indirectness (short follow-up times).

    References

    • El-Sayeh HG, Morganti C. Aripiprazole for schizophrenia. Cochrane Database Syst Rev 2006 Apr 19;(2):CD004578. [PubMed]
    • Bhattacharjee J, El-Sayeh HG. Aripiprazole versus typicals for schizophrenia. Cochrane Database Syst Rev 2008 Jan 23;(1):CD006617. [PubMed]
    • Khanna P, Suo T, Komossa K et al. Aripiprazole versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev 2014;1():CD006569. [PubMed]

Primary/Secondary Keywords