1. Valproate compared to carbamazepine for acute mania in adults.
| Valproate compared to carbamazepine for acute mania | ||||||
| Patient or population: Adults (aged 18 and over) with acute mania Setting: Inpatient Intervention: Valproate Comparison: Carbamazepine | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Quality of the evidence (GRADE) | Comments | |
| Risk with carbamazepine | Risk with valproate | |||||
| Response rate at 4 weeks (primary efficacy outcome) | Study population | OR 2.41 (0.52 to 11.10) | 30 (1 RCT) | ⊕⊝⊝⊝ VERY LOWa,b | The evidence is very uncertain about the relative effects of valproate and carbamazepine on response rates. | |
| 533 per 1000 | 734 per 1000 (373 to 927) | |||||
| Number with any adverse event at 4 weeks (primary tolerability outcome) | Study population | OR 0.13 (0.02 to 0.82) | 30 (1 RCT) | ⊕⊕⊝⊝ LOWa,b,c | Valproate may cause fewer people to have side effects than carbamazapine, but the evidence is uncertain. | |
| 533 per 1000 | 129 per 1000 (22 to 484) | |||||
| Individual adverse events ‐ Lethargy At 4 weeks (secondary tolerability outcome) |
Study population | OR 0.14 (0.01 to 1.42) |
30 (1 RCT) | ⊕⊕⊝⊝ LOWa,b,c | Valproate may cause fewer people to have less lethargy than carbamazapine, but the evidence is uncertain. | |
| 333 per 1000 | 65 per 1000 (5‐415) |
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| Change in symptom severity at 4 weeks (secondary efficacy outcome) | The mean change in symptom severity for carbamazepine at 4 weeks was ‐ 20.8. | MD ‐ 12.00 (‐ 21.82 to ‐ 2.18 ) | ‐ | 30 (1 RCT) | ⊕⊝⊝⊝ VERY LOWa,b | Valproate may cause a greater reduction in manic symptoms than carbamazapine, but the evidence is very uncertain. |
| Dropout rate ‐ All‐cause At 4 weeks (secondary acceptability outcome) |
Study population | OR 1.00 (0.17 to 5.98) | 30 (1 RCT) | ⊕⊝⊝⊝ VERY LOWa,b,d | The evidence is very uncertain about the relative effects of valproate and carbamazapine on dropout rates. | |
| 200 per 1000 | 200 per 1000 (41 to 599) | |||||
| *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). CI: Confidence interval; OR: Odds ratio; RCT: randomised controlled trial | ||||||
| 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 | ||||||
aEvidence downgraded by one level as > 30% of trials were at serious risk of bias. Vasudev 2000 at serious risk of bias, as at high risk of selection and other bias and at unclear risk of bias on performance and reporting biases. bEvidence downgraded by two levels for imprecision, due to single study and small study size. cEvidence upgraded by one level as large effect, RR < 0.5. dEvidence downgraded by one level for imprecision due to wide confidence interval ‐ Includes both no effect and OR of 4/0.25.