Table 3. Ziprasidone versus placebo on QT interval in people with mental disorders.
| Outcome | Risk with intervention per 1,000 | Risk with comparator per 1,000 | Relative measure of association | Number of participants | Quality (grade) | Comments† |
|---|---|---|---|---|---|---|
| Ziprasidone monotherapy versus placebo | ||||||
| QT change from baseline | NR | NR | MD 3.90 (2.43, 5.37); SMD 0.19 (0.12, 0.26) | 5,217 (44)* | Low | Favors placebo |
| Peak measured QTc ≥450 msec | 8 | 10 | RR 0.78 (0.37, 1.62) | 5,217 (44)* | Very low | No difference |
| Peak measured QTc ≥480 msec | 0 | 0 | RR 0.64 (0.03, 15.58) | 5,217 (44)* | Very low | No difference |
| Peak measured QTc ≥500 msec | 0 | 0 | RR 0.64 (0.03, 15.58) | 5,217 (44)* | Very low | No difference |
| Maximal QTc change from baseline ≥30 msec | 90 | 59; attributable events per 1,000 treated 31 [14, 49] | RR 1.52 (1.16, 2.01); NNT 32 [21, 74] | 5,217 (44)* | Low | Favors placebo |
| Maximal QTc change from baseline ≥60 msec | 7 | 8 | RR 0.91 (0.40, 2.06) | 5,217 (44)* | Very low | No difference |
| Maximal QTc change from baseline ≥75 msec | 3 | 1 | RR 2.54 (0.33, 19.50) | 5,217 (44)* | Very low | No difference |
| Ziprasidone plus lamotrigine versus placebo plus lamotrigine | ||||||
| QTc change from baseline | NR | NR | MD 2.00 (−4.53, 8.53); SMD 0.13 (−0.30, 0.57) | 82 (44)* | Very low | No difference |
| Peak measured QTc ≥450 msec | 24 | 24 | RR 1.00 (0.06, 15.45) | 82 (44)* | Very low | No difference |
| Peak measured QTc ≥480 msec | 0 | 0 | RR undetermined | 82 (44)* | Very low | No difference |
| Peak measured QTc ≥500 msec | 0 | 0 | RR Undetermined | 82 (44)* | Very low | No difference |
| Maximal QTc change from baseline ≥30 msec | 0 | 49 | RR 0.20 (0.01, 4.04) | 82 (44)* | Very low | No difference |
| Maximal QTc change from baseline ≥60 msec | 0 | 0 | RR undetermined | 82 (44)* | Very low | No difference |
| Maximal QTc change from baseline ≥75 msec | 0 | 0 | RR undetermined | 82 (44)* | Very low | No difference |
| Ziprasidone plus lithium versus placebo plus lithium | ||||||
| QTc change from baseline | NR | NR | MD 2.10 (−1.32, 5.52); SMD 0.10 (−0.06, 0.26) | 608 (44)* | Low | No difference |
| Peak measured QTc ≥450 msec | 27 | 19 | RR 1.43 (0.48, 4.21) | 608 (44)* | Very low | No difference |
| Peak measured QTc ≥480 msec | 3 | 0 | RR 2.38 (0.10, 58.25) | 608 (44)* | Very low | No difference |
| Peak measured QTc ≥500 msec | 0 | 0 | RR undetermined | 608 (44)* | Very low | No difference |
| Maximal QTc change from baseline ≥30 msec | 112 | 86 | RR 1.31 (0.80, 2.15) | 608 (44)* | Very low | No difference |
| Maximal QTc change from baseline ≥60 msec | 12 | 7 | RR 1.59 (0.29, 8.60) | 608 (44)* | Very low | No difference |
| Maximal QTc change from baseline ≥75 msec | 3 | 7 | RR 0.40 (0.04, 4.35) | 608 (44)* | Very low | No difference |
| Ziprasidone plus valproate versus placebo plus valproate | ||||||
| QTc change from baseline | NR | NR | MD 3.40 (0.71, 6.09); SMD 0.20 (0.04, 0.36) | 631 (44)* | Low | Favors placebo |
| Peak measured QTc ≥450 msec | 21 | 0 | RR 10.81 (0.63, 186.38) | 631 (44)* | Very low | No difference |
| Peak measured QTc ≥480 msec | 0 | 0 | RR undetermined | 631 (44)* | Very low | No difference |
| Peak measured QTc ≥500 msec | 0 | 0 | RR undetermined | 631 (44)* | Very low | No difference |
| Maximal QTc change from baseline ≥30 msec | 60 | 37 | RR 1.62 (0.76, 3.45) | 631 (44)* | Very low | No difference |
| Maximal QTc change from baseline ≥60 msec | 0 | 0 | RR undetermined | 631 (44)* | Very low | No difference |
| Maximal QTc change from baseline ≥75 msec | 0 | 0 | RR undetermined | 631 (44)* | Very low | No difference |
*, individual patient data network meta-analysis of 40 Pfizer-sponsored phase II–IV RCTs in schizophrenia or bipolar disorder patients including 5 pediatric RCTs; †, we concluded that there is no difference in outcomes between active and control interventions based on P>0.05 and inability to reject null hypotheses but without post-hoc analysis of the statistical power to detect true differences. 95% confidence interval in ()/[ ]; GRADE, Grading of Recommendations Assessment, Development and Evaluation; NNT, number needed to treat to achieve an outcome in one patient; NNT is calculated as 1/absolute risk difference; attributable events per 1,000 treated as the number of excessive or avoided events per 1,000 treated that are attributed to active treatment; attributable events per 1,000 treated are calculated as absolute rate difference multiplied by 1,000; RCT, randomized controlled trial; RR, relative risk; MD, mean difference; SMD, standardized mean difference between intervention and comparator where the magnitude of the effect is defined as small (SMD, 0–0.5 standard deviations), moderate (SMD, 0.5–0.8 standard deviations), and large (SMD >0.8 standard deviations); QTc, corrected QT interval; NR, not reported.