Summary of findings 5. CLOZAPINE + ZIPRASIDONE versus CLOZAPINE + QUETIAPINE (Wen 2015).

Clozapine + ziprasidone versus clozapine + quetiapine for treatment‐resistant schizophrenia
Patient or population: people with treatment‐resistant schizophrenia Setting: inpatients and outpatients Intervention: ziprasidone (+ CLO) Comparison: quetiapine (+ CLO)
Outcomes	Anticipated absolute effects* (95% CI)		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with quetiapine (+ CLO)	Risk with ziprasidone (+ CLO)
Clinical response: no clinically significant response in mental state: ≥ 50% reduction in PANSS total score Medium term (12 weeks)	Study population		RR 0.54 (0.35 to 0.81)	63 (1 RCT)	⊕⊕⊝⊝ Low 1,2,3,4	‐
	844 per 1000	456 per 1000 (295 to 683)
	Moderate
	844 per 1000	456 per 1000 (295 to 683)
Adverse effects: weight gain	See comment	See comment	Not estimable	‐	‐	No data reported.
Clinical response: mean score/change in global state: mean CGI‐S score (high = poor) Medium term (12 weeks)	The mean score/change in global state (CGI‐S) ‐ medium term (12 weeks) was 0	The mean score/change in global state (CGI‐S) ‐ medium term (12 weeks) in the intervention group was 0.7 fewer (1.18 fewer to 0.22 fewer)	‐	60 (1 RCT)	⊕⊕⊝⊝ Low 1,2,4,5	‐
Clinical response: mean score/change in mental state: mean PANSS total score (high = poor) Medium term (12 weeks)	The mean score/change in mental state (PANSS total) ‐ medium term (12 weeks) was 0	The mean score/change in mental state (PANSS total) ‐ medium term (12 weeks) in the intervention group was 12.3 fewer (22.43 fewer to 2.17 fewer)	‐	60 (1 RCT)	⊕⊕⊝⊝ Low 1 2 3 4	‐
Leaving the study early: acceptability of treatment ‐ as measured by completion of trial	Study population		RR 0.52 (0.05 to 5.41)	63 (1 RCT)	⊕⊝⊝⊝ Very low 1,2,6,7	‐
	63 per 1000	33 per 1000 (3 to 338)
	Moderate
	63 per 1000	33 per 1000 (3 to 338)
Service utilisation outcomes: hospital admission or days in hospital	See comment	See comment	Not estimable	‐	‐	No data reported.
Quality of life/satisfaction with care for either recipients of care or carers: significant change in quality of life/satisfaction	See comment	See comment	Not estimable	‐	‐	No data reported.
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CGI ‐S: Clinical Global Impression – Severity; CI: confidence interval; CLO: clozapine; PANSS: Positive and Negative Syndrome Scale; RCT: randomised controlled trial; RR: risk ratio; SD: standard deviation.
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect. Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.

¹ Risk of bias: downgraded by 2 levels because unclear (so potentially high) risk of biases (selection, performance, reporting).

² Inconsistency and publication bias: not applicable (no meta‐analysis).

³ Indirectness: not downgraded because good applicability in terms of participants and interventions and rating scale measures a participant‐important outcome (mental state).

⁴ Imprecision: not downgraded because powered to detect difference and narrow CI.

⁵ Indirectness: not downgraded because good applicability (participants and interventions) and rating scale measures a participant‐important outcome (global state).

⁶ Indirectness: downgraded by 1 level because leaving the study early surrogate measure for participant‐important outcome (acceptability of treatment).

⁷ Imprecision: downgraded by 2 levels because underpowered to detect difference and CI around relative effect includes appreciable benefit and harm (from less likely to leave study early to five times more likely to leave study early).