Quetiapine for Schizophrenia

A Cochrane review [Abstract] 1 included 43 studies with a total of 7 217 subjects. Most studies were from China and conducted in an inpatient setting. Thirty-five studies were short term with a duration range of 4 to 12 weeks.The percentages of participants leaving the studies early were similar (36.5% in quetiapine vs. 36.9% in typical antipsychotics group). No significant difference between groups was apparent for leaving early due to any reason (RR 0.91, CI 0.81 to 1.01; 23 trials, n = 3 576), however, fewer participants in the quetiapine group left the studies early due to adverse events (RR 0.48, CI 0.30 to 0.77; 15 trials, n = 3 010). Overall global state was similar between groups (RR 0.96, CI 0.75 to 1.23; 16 trials, n = 1 607). There was no significant difference in positive symptoms (PANSS positive subscore: MD 0.02 CI -0.39 to 0.43; 22 trials, n = 1 934). General psychopathology was equivocal (PANSS general psychopathology subscore: MD -0.20, CI -0.83 to 0.42; 18 trials, n = 1 569) between quetiapine and typical antipsychotics. However, quetiapine was statistically significantly more efficacious for negative symptoms (PANSS negative subscore: MD -0.82, CI -1.59 to -0.04; 22 trials, n = 1 934), but 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 (RR 0.76, CI 0.64 to 0.90, NNTH 10, CI 8 to 17; 9 trials, n = 1 985), less abnormal ECG (RR 0.38, CI 0.16 to 0.92, NNTH 8, CI 4 to 55; 2 trials, n = 165), fewer overall extrapyramidal effects (RR 0.17, CI 0.09 to 0.32, NNTH 3, CI 3 to 3; 8 trials, n = 1 095) and fewer specific extrapyramidal effects including akathisia, parkinsonism, dystonia and tremor. Moreover, it might cause lower prolactin level (MD -16.20, CI -23.34 to -9.07; 4 trials, n = 1034) and less weight gain compared with some typical antipsychotics in the short term (RR 0.52, CI 0.34 to 0.80, NNTH 8, CI 6 to 15; 9 trials, n = 866). 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.

Another Cochrane review 2 included 35 RCTs. Twenty-six studies were short term with a duration of 2 to 12 weeks. Studies compared quetiapine with aripiprazole, clozapine, olanzapine, paliperidone, risperidone and ziprasidone. Seven trials were conducted in an inpatient or outpatient setting and 16 studies exclusively in an inpatient setting. Fifteen studies were short term with a duration of 2-12 weeks. In thirteen studies the drop-out rate was higher than 30% (50.2% overall). For 15 trials the reporting of pre-defined outcomes was incomplete.

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

Comment:The quality of evidence is downgraded by limitations in study quality (unclear allocation concealment, high drop-out rate) and indirectness (differences in patients: assessed considerably in an inpatient setting and short follow-up period).

References

• Suttajit S, Srisurapanont M, Xia J et al. Quetiapine versus typical antipsychotic medications for schizophrenia. Cochrane Database Syst Rev 2013;5():CD007815. [PubMed]
• Asmal L, Flegar SJ, Wang J et al. Quetiapine versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev 2013;11():CD006625. [PubMed].