4. Valproate + olanzapine compared to olanzapine alone for acute mania in adults.
| Valproate + olanzapine compared to olanzapine alone for acute mania | ||||||
| Patient or population: Adults (aged 18 and over) with acute mania Setting: Inpatient Intervention: Valproate and olanzapine Comparison: Olanzapine alone | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Quality of the evidence (GRADE) | Comments | |
| Risk with olanzapine alone | Risk with valproate + olanzapine | |||||
| Response rate (primary efficacy outcome) | ‐ | ‐ | ‐ | ‐ | ‐ | Not reported |
| Number of participants with any adverse event (primary tolerability outcome) | ‐ | ‐ | ‐ | ‐ | ‐ | Not reported |
| Individual adverse events ‐ Somnolence At 3 weeks |
Study population | OR 0.79 (0.30 to 2.06) | 80 (1 RCT) | ⊕⊕⊝⊝ LOWa | The evidence is uncertain about the relative effects of valproate with olanzapine compared to olanzapine alone on somnolence. | |
| 325 per 1,000 | 276 per 1,000 (126 to 498) | |||||
| Individual adverse events ‐ Weight gain At 3 weeks |
Study population | OR 1.31 (0.47 to 3.61) | 80 (1 RCT) | ⊕⊕⊝⊝ LOWa | The evidence is uncertain about the relative effects of valproate with olanzapine compared to olanzapine alone on weight gain. | |
| 725 per 1000 | 775 per 1000 (553 to 905) | |||||
| Change in symptom severity at 3 weeks (secondary efficacy outcome) |
The mean change in symptom severity for olanzapine alone at 3 weeks was ‐ 20.74. | MD ‐ 2.76 (‐ 9.17 to 3.65) | ‐ | 76 (1 RCT) | ⊕⊕⊝⊝ LOWa,b | The evidence is uncertain about the relative effects of valproate with olanzapine compared to olanzapine alone on decreasing manic symptoms. |
| Dropout ‐ All‐cause At 3 weeks (secondary acceptability outcome) |
Study population | OR 2.05 (0.18 to 23.59) | 80 (1 RCT) | ⊕⊝⊝⊝ VERY LOWa,b | The evidence is very uncertain about the relative effects of valproate with olanzapine compared to olanzapine alone on dropout rates. | |
| 25 per 1000 | 50 per 1000 (5 to 377) | |||||
| *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 two levels for imprecision, due to single study and small study size. bEvidence downgraded by one level for imprecision, due to wide confidence interval; OR includes both 4 and 0.25